Regular physical activity is associated with enhanced plasticity in the motor cortex, but the effect of a single session of aerobic exercise on neuroplasticity is unknown. The aim of this study was to compare corticospinal excitability and plasticity in the upper limb cortical representation following a single session of lower limb cycling at either low or moderate intensity, or a control condition. We recruited 25 healthy adults to take part in three experimental sessions. Cortical excitability was examined using transcranial magnetic stimulation to elicit motor-evoked potentials in the right first dorsal interosseus muscle. Levels of serum brain-derived neurotrophic factor and cortisol were assessed throughout the experiments. Following baseline testing, participants cycled on a stationary bike at a workload equivalent to 57% (low intensity, 30 min) or 77% age-predicted maximal heart rate (moderate intensity, 15 min), or a seated control condition. Neuroplasticity within the primary motor cortex was then examined using a continuous theta burst stimulation (cTBS) paradigm. We found that exercise did not alter cortical excitability. Following cTBS, there was a transient inhibition of first dorsal interosseus motor-evoked potentials during control and low-intensity conditions, but this was only significantly different following the low-intensity state. Moderate-intensity exercise alone increased serum cortisol levels, but brain-derived neurotrophic factor levels did not increase across any condition. In summary, low-intensity cycling promoted the neuroplastic response to cTBS within the motor cortex of healthy adults. These findings suggest that light exercise has the potential to enhance the effectiveness of motor learning or recovery following brain damage.

Primary motor cortex neuroplasticity is reduced in old adults, which may contribute to the motor deficits commonly observed in the elderly. Previous research in young subjects suggests that the neuroplastic response can be enhanced using non-invasive brain stimulation (NIBS), with a larger plastic response observed following priming with both long-term potentiation (LTP) and depression (LTD)-like protocols. However, it is not known if priming stimulation can also modulate plasticity in older adults. To investigate if priming NIBS can be used to modulate motor cortical plasticity in old subjects. In 16 young (22.3 ± 1.0 years) and 16 old (70.2 ± 1.7 years) subjects, we investigated the response to intermittent theta burst stimulation (iTBS; LTP-like) when applied 10 min after sham stimulation, continuous TBS (cTBS; LTD-like) or an identical block of iTBS. Corticospinal plasticity was assessed by recording changes in motor evoked potential (MEP) amplitude. In young subjects, priming with cTBS (cTBS + iTBS) resulted in larger MEPs than priming with either iTBS (iTBS + iTBS; P = 0.001) or sham (sham + iTBS; P < 0.0001), while larger MEPs were seen following iTBS + iTBS than sham + iTBS (P < 0.0001). In old subjects, the response to iTBS + iTBS was not different to sham + iTBS (P > 0.9), whereas the response to cTBS + iTBS was reduced relative to iTBS + iTBS (P = 0.02) and sham + iTBS (P = 0.04). Priming TBS is ineffective for modifying M1 plasticity in older adults, which may limit the therapeutic use of priming stimulation in neurological conditions common in the elderly.

Long-interval intracortical inhibition (LICI) is a transcranial magnetic stimulation (TMS) paradigm that uses paired magnetic stimuli separated by 100-200 ms to investigate the activity of cortical GABAergic interneurons. While commonly applied, the mechanisms contributing to LICI are not well understood, and growing evidence suggests that inhibition observed at different interstimulus intervals (ISI) may involve non-identical processes. This study aims to utilise combined TMS-EEG to more thoroughly characterise LICI at different ISIs, as the TMS-evoked EEG potential (TEP) can provide more direct insight into the cortical response to stimulation that is not subject to variations in spinal cord excitability that can confound the motor evoked potential (MEP). In 12 subjects (22.6 ± 0.9 years), LICI was applied using two ISIs of 100 ms (LICI100) and 150 ms (LICI150), while TEPs were recorded using simultaneous high-definition EEG. Analysis of EEG data within a region of interest (C3 electrode) showed that test alone stimulation produced three consistent TEP peaks (corresponding to P30, N100 and P180) that were all significantly inhibited following paired-pulse stimulation. However, for P30, inhibition varied between LICI conditions, with reduced amplitude following LICI100 (P = 0.03) but not LICI150 (P = 0.3). In contrast, the N100 and P180 were significantly reduced by LICI at both intervals (all P-values < 0.05). In addition, topographical analyses suggested that the global change in P30, N40 and P180 differed between LICI conditions. These findings suggest that LICI100 and LICI150 reflect complex measurements of cortical inhibition with differential contributions from comparable circuits.

Effects of age on the assessment of intracortical inhibition with paired-pulse transcranial magnetic stimulation (TMS) have been variable, which may be due to between-study differences in test TMS intensity and test motor evoked potential (MEP) amplitude. To investigate age-related differences in short- (SICI) and long-interval intracortical inhibition (LICI) across a range of test TMS intensities and test MEP amplitudes. In 22 young and 18 older subjects, SICI and LICI were recorded at a range of test TMS intensities (110%-150% of motor threshold) while the first dorsal interosseous (FDI) muscle was at rest, or producing a precision grip of the index finger and thumb. Data were subsequently compared according to the amplitude of the MEP produced by the test alone TMS. When pooled across all test TMS intensities, SICI in resting muscle and LICI in active muscle were similar in young and older adults, whereas SICI in active muscle and LICI in resting muscle were reduced in older adults. Regrouping data based on test MEP amplitude demonstrated similar effects of age for SICI and LICI in resting muscle, whereas more subtle differences between age groups were revealed for SICI and LICI in active muscle. Advancing age influences GABA-mediated intracortical inhibition, but the outcome is dependent on the experimental conditions. Age-related differences in SICI and LICI were influenced by test TMS intensity and test MEP amplitude, suggesting that these are important considerations when assessing intracortical inhibition in older adults, particularly in an active muscle.