Novel evidence of age-related cortical and subcortical constraints in cross-education

Cross-education (CE), the phenomenon whereby unilateral strength training induces neuromuscular adaptations in the contralateral limb, is underpinned by distributed cortical and subcortical plasticity. This study evaluated acute neural responses to a single bout of metronome-paced unilateral strength training in younger (n = 17; 27 ± 6 years) and older adults (n = 18; 67 ± 5 years). Neurophysiological assessments included corticospinal excitability and inhibition via transcranial magnetic stimulation (TMS), intracortical inhibition through short-interval intracortical inhibition (SICI), and reticulospinal drive using the StartReact paradigm. Following training, younger adults exhibited a significant reduction in the responsiveness of intracortical inhibitory interneurons, reflected as a release of SICI (pre: 58.05, 95% CI 48.83-67.27; post: 68.88, 95% CI 59.69-78.06; p < 0.01), consistent with diminished GABA-_A -mediated synaptic efficacy. In contrast, older adults showed no changes (pre: 65.73, 98% CI 57.00-74.46; post: 60.71, 95% CI 52.03-69.39; p = 0.13), indicating no significant modulation of GABA-_A-mediated inhibitory circuits with ageing. No changes in corticospinal excitability were observed in either group. StartReact responses remained stable across timepoints, implying insufficient acute engagement of the reticulospinal tract. Notably, younger adults exhibited a decline in rate of force development (RFD; pre: 912.70, 95% CI 821.97-1003.44 N/s; post: 791.02, 95% CI 700.29-881.75 N/s; p < 0.05), potentially reflecting central fatigue, while older adults displayed no significant change. These findings reveal age-dependent asymmetries in the neural mechanisms underpinning CE, with older adults exhibiting a lack of adaptive modulation in intracortical and subcortical systems. The absence of reticulospinal adaptation underscores the need for sustained or higher-intensity training stimuli to elicit subcortical plasticity. These results inform the development of targeted, age-sensitive neuromuscular rehabilitation strategies.