Neural mechanisms mediating cross education: With additional considerations for the ageing brain

•The contralateral benefits of unimanual limb training are preserved in later life.•Ipsilateral descending pathways are unlikely to contribute to cross education (CE).•Adaptations local to the untrained M1 do not appear to mediate CE.•CE in older persons may be characterised by altered engagement of premotor areas.•Transcallosal and thalamocortical projections are candidate mediators of CE. CALVERT, G.H.M., and CARSON, R.G. Neural mechanisms mediating cross education: With additional considerations for the ageing brain. NEUROSCI BIOBEHAV REV 21(1) XXX-XXX, 2021. - Cross education (CE) is the process whereby a regimen of unilateral limb training engenders bilateral improvements in motor function. The contralateral gains thus derived may impart therapeutic benefits for patients with unilateral deficits arising from orthopaedic injury or stroke. Despite this prospective therapeutic utility, there is little consensus concerning its mechanistic basis. The precise means through which the neuroanatomical structures and cellular processes that mediate CE may be influenced by age-related neurodegeneration are also almost entirely unknown. Notwithstanding the increased incidence of unilateral impairment in later life, age-related variations in the expression of CE have been examined only infrequently. In this narrative review, we consider several mechanisms which may mediate the expression of CE with specific reference to the ageing CNS. We focus on the adaptive potential of cellular processes that are subserved by a specific set of neuroanatomical pathways including: the corticospinal tract, corticoreticulospinal projections, transcallosal fibres, and thalamocortical radiations. This analysis may inform the development of interventions that exploit the therapeutic utility of CE training in older persons.