Interventions to manipulate neuroplasticity in ageing

Gamage, Nishadi

Interventions to manipulate neuroplasticity in ageing

Publication Date

July 27, 2026

Creator

Gamage, Nishadi

Neurophysiology of Human Movement Laboratory, Faculty of Health and Medical Sciences, University of Adelaide, Australia & Centre of Metabolism, Ageing & Physiology, School of Medicine, University of Nottingham, United Kingdom

Abstract

Ageing is associated with a decline in brain and skeletal muscle function, which leads to loss of independence and a reduction in general health status. Neuroplasticity refers to the capacity of the nervous system to change in response to pathological (injury or disease) or physiological events (learning from experience). Age-related decline in neuroplasticity limits motor function improvements and learning, which has an impact on functional recovery following brain injury in older adults. Evidence suggests that exercise and motor training can enhance brain function and minimise age-associated decline in the neuromusculoskeletal system. Therefore, the experimental studies included in this thesis aimed to evaluate neuroplasticity, including alterations in the central nervous system and neuromuscular system in healthy older adults through various interventions. Chapter 2 (conducted at the University of Nottingham) examined neuromuscular function and the cross-limb transfer effect in older adults, where these changes were assessed following an acute unilateral resistance exercise. This study provides insights into functional properties (force production) and motor unit characteristics using high-density surface electromyography (HDsEMG) and intramuscular electromyography (iEMG). This study demonstrated that acute unilateral resistance exercise leads to a bilateral reduction in force production in healthy older adults, indicating a cross-limb transfer effect. The motor unit level adaptations were evident only in the exercised limb, and the mechanisms underlying the functional changes in the non-exercised limb remain uncertain. Chapter 3 (conducted at the University of Adelaide) examined ‘age-related changes in brain and motor function’, during which the impact of a novel non-invasive brain stimulation technique (i.e., theta-gamma transcranial alternating current stimulation; theta-gamma tACS) on motor performance was evaluated and compared between young and older adults. The study utilised a unilateral ballistic thumb task performed concurrently with stimulation applied to the contralateral primary motor cortex. Both young and older adults showed improvement in motor performance with theta-gamma tACS, with effects lasting up to 60 minutes. Furthermore, corticospinal excitability (assessed using transcranial magnetic stimulation; TMS) was greater following theta-gamma tACS compared to sham stimulation. These findings suggest that theta-gamma tACS may offer a promising approach to counteract some aspects of motor deficits associated with ageing. The final experimental chapter (Chapter 4, conducted at the University of Adelaide) evaluated ‘ageing, neuromuscular function and cross-limb transfer effect’, integrating these approaches by assessing the potential of tACS to influence ballistic motor performance and cross-limb transfer in healthy older adults. Three experimental groups received stimulation to primary motor cortex (theta-gamma tACS, theta tACS, or sham tACS) during performance of a unilateral ballistic thumb task. The study results indicated that ballistic motor performance improved in all tACS conditions, with the greatest effect following theta tACS for both hands. Training-induced corticospinal excitability was increased for theta tACS only, while there was a correlation between the trained and untrained gains in motor performance that was significant for theta-gamma tACS only. These findings suggest tACS has the potential to facilitate ballistic motor performance and promote cross-limb transfer effect in older adults. Overall, this thesis provides novel insights into techniques that could be used to mitigate some aspects of age-related neuromuscular deficits and further supports the understanding of neurophysiological modifications associated with ageing and motor performance following different interventions. These findings have potential implications for rehabilitation following neurological disorders (e.g., stroke) and orthopaedic conditions (e.g., single-limb fractures), where non-invasive brain stimulation or training of the unaffected limb can be used to facilitate motor performance gains of the affected limb. This thesis also emphasises the necessity for deeper insights into the neural mechanisms underlying cross-limb transfer of resistance exercise and ballistic motor performance, as well as the requirement to develop more effective non-invasive brain stimulation interventions to improve motor performance in older adults.

Item Type

ethesis

Thesis Type

PhD

Supervisors

Piasecki, Mathew