The Australian population is ageing, and advancing age can be viewed as one model of maladaptive neuroplasticity. That is, there are structural and functional changes within the CNS that play a role in a host of functional impairments, contributing to a loss of independence and reduced quality of life in older adults. For example, age-related reductions in muscle strength and power, impaired balance and gait, and diminished proprioceptive acuity are associated with structural reductions in neurological integrity. Importantly, older adults can also experience adaptive neuroplasticity in response to neuromodulatory stimuli, and forms of exercise and motor training involving novel or skilled tasks are examples of such stimuli. This is evidenced by training-related changes in transcranial magnetic stimulation (TMS) measures such as corticospinal excitability (i.e. recruitment curve (RC) parameters and motor evoked potential (MEP) amplitude) and short-interval intracortical inhibition (SICI) confined to the primary motor cortex (M1). However, most research to date has focused on young adults, and little is known regarding the time-course of adaptations in older adults following various training interventions. Given the necessity for motor tasks to be ‘centrally demanding’ in order to exploit neural adaptations, in addition to the aforementioned age-related deficits (reduced muscle strength, balance and proprioceptive acuity), interventions such as challenging balance (BAL), visuomotor (VIS), and externally-paced strength training (EP-ST) may be ideal contenders for counteracting or preventing maladaptive neuroplasticity and improving functional outcomes for older adults. Therefore, the overarching theme of this thesis was to determine age-related differences in neurological function in young and older adults as measured by TMS, and then determine the efficacy of BAL, VIS and EP-ST at inducing both physical and functional improvements as well as causing transient and residual changes in neurological function in older adults.

The first study (chapter three) was a cross-sectional comparison of neurophysiological function (as measured by TMS) and performance in various functional tasks between young and older adults. Despite evidence from previous studies of relationships between structural brain measures (grey/white matter volume and white matter hyperintensities) and functional performance, and mixed findings regarding age-related changes in neurophysiological function, the relationship between neurophysiological function and performance in functional tasks had not been sufficiently investigated, particularly for the lower-limb. This study compared measures of corticospinal excitability (resting and active motor threshold (RMT/AMT) and RC parameters), SICI and performance in a host of lower-limb and functional tasks (dynamic strength, balance, visuomotor tracking, six minute walk and stair climb) between young (n = 15;​ 23 ± 5 years) and older (n = 17;​ 71 ± 5 years) adults. Further, this study sought to explore whether any age-related differences in neurological variables were associated with physical or functional performance. Older adults performed consistently worse in all lower-limb tasks, suggesting that the tests used were sensitive to the effects of ageing. Older adults also required significantly greater stimulus intensities to elicit MEPs compared to young adults (all P < 0.05), but there were no age-related differences in SICI or parameters of the RC (all P > 0.05). This suggests that perhaps corticospinal excitability measured using TMS in an active muscle may not be as impaired with advancing age as expected, and that other mechanisms such as cortical thinning (i.e. increasing the coil-to-cortex distance) may be a greater contributor to the increased stimulus intensities required to elicit MEPs in older adults. Finally, AMT was associated with visuomotor tracking error at five seconds in tasks two and three, and SICI was associated with stair climb time and visuomotor tracking error at five seconds in task two;​ but these relationships were only observed in older adults. This supports differential mechanisms for the performance of lower-limb tasks between young and older adults, which is important to know when interpreting the contributing factors to motor performance. Overall, this study provided insight into the relationship between age-related differences in neurophysiological function and functional performance, and the findings from this study formed the basis for studies two and three.

The second study (chapter four) examined the acute effects (up to 60 minutes post) of a single 45 minute bout of three different centrally demanding motor training tasks:​ BAL (n = 12;​ 69 ± 6 years), VIS (n = 12;​ 72 ± 6 years) and EP-ST (n = 9;​ 70 ± 6 years) on corticospinal excitability and SICI in older adults by comparing to a non-training control (CTRL) group (n = 8;​ 69 ± 4 years). There is evidence that older adults can experience neuroplasticity following various experimentally induced or use-dependent neuromodulatory protocols, but they may be less responsive or require a greater duration of stimulus to achieve such results. This study sought to examine and compare the efficacy of these training modalities, which are believed to involve complex neural stimuli, in inducing transient neuroplastic changes (i.e. altered MEP amplitude at 120% or 160% of AMT, or SICI) in older adults. This was assessed over a time-course of five, 30 and 60 minutes post-training in order to examine the immediate effects after a single training session, and the pattern of changes over time. The findings showed that all three modes of training significantly reduced SICI compared to baseline and CTRL for up to one hour following the respective training sessions (45 minute duration), but most importantly there were no differences between training groups. However, increases in MEP amplitude of up to 49% at 120% of AMT and 18% at 160% of AMT were not statistically significant, despite large effect sizes. This was most likely due to large inter-individual variability in the responses. This study demonstrated for the first time that a single session of BAL, VIS and EP-ST could reduce SICI in older adults, and supports the capacity for each of these training modes to provide complex neuromodulatory stimuli to the central nervous system (CNS). Therefore, each of these modes of training may be effective at counteracting age-related maladaptive neuroplasticity whilst also likely targeting physical and functional deficits that commonly occur in older adults. This study provided important new knowledge about how well different targeted training modalities can induce use-dependent neuroplasticity in older adults, and how changes in neurophysiological function may be exploited over time to improve functional ability in older adults, which was examined in study three.

Study three (chapter five) investigated the long-term neurophysiological and functional adaptations experienced by older adults during and after a 12 week training intervention of BAL (n = 10;​ 68 ± 6 years), VIS (n = 9;​ 72 ± 5 years) or EP-ST (n = 9;​ 70 ± 6 years) compared to a non-training CTRL group (n = 8;​ 69 ± 4 years). Fully supervised group training (45 minutes duration) occurred at the same time of day three days per week, and data were collected every four weeks for the duration of the training period (i.e. baseline, four weeks, eight weeks and 12 weeks) within 12-24 hours after the preceding training session. A follow-up testing session also occurred four weeks after the intervention period ended (i.e. retention testing at 16 weeks) to determine any long-term residual benefits. There were mode-specific improvements in lower-limb tasks, with the EP-ST group improving muscle strength compared to BAL, VIS and CTRL (all P < 0.05), and the BAL group improving balance performance compared to EP-ST, VIS and CTRL (all P < 0.05). However, all training groups improved visuomotor tracking performance compared to CTRL at the 30 s time point in tasks two and three, with no between-group differences between BAL, VIS or EP-ST. This indicates that all of these modes of training imposed a unique challenge to sensorimotor integration, resulting in improved proprioceptive acuity. Similarly, all training groups also improved six minute walk performance and stair climb time to a similar extent compared to baseline and CTRL, with performance peaking at eight weeks and no further improvements despite ongoing training. The lack of difference between training groups was somewhat unexpected, but may in-part be explained by psychosocial factors improving selfefficacy and confidence in completing functional tasks. Interestingly, all training groups also experienced reductions in SICI in the first eight weeks, after which time responses failed to change any further despite ongoing exposure to the training stimuli. Slope of the TMS RC significantly increased after four weeks in both the EP-ST and VIS groups, then returned to baseline levels by eight weeks, and increased again at 12 weeks, suggesting changes in the activation patterns of corticospinal neurons in these groups that probably reflect transition from skill acquisition to the consolidation of skills. There were no other changes in corticospinal excitability (RC parameters) for any group at any time point. Follow-up testing at 16 weeks revealed that training-related changes in lower-limb task performance were sustained, but all neurological measures had returned to baseline with the exception of SICI for the VIS group, and the slope of the RC for the EP-ST group (although they were approaching baseline levels). The findings of this study show for the first time that older adults can experience adaptive neuroplasticity measured by TMS that is representative of longer-term residual changes within the CNS as a result of the BAL, VIS and EP-ST training. This, in combination with the similar functional improvements between groups, can help professionals to prescribe highly personalised training interventions that are dependent upon a client’s specific physical deficits (e.g. reduced muscle strength, poor balance) without compromising functional or neural outcomes for older adults.

Collectively, these findings provide insight into the functional relevance of age-related differences in corticospinal function and support the potential for BAL, VIS and EP-ST to exploit the flexibility of older adults’ CNS to adapt in response to challenging stimuli. Importantly, Study 2 showed that older adults can rapidly adapt to these use-dependent neuromodulatory protocols, with neurological changes detected as early as five minutes following the cessation of the training stimuli. In contrast, Study 3 demonstrated a different mechanism for neuroplasticity in older adults, with testing occurring 12-24 hours after the cessation of the training stimuli to ensure that results reflected adaptations within the CNS rather than the transient effects of the training itself. This offers promising evidence of the flexibility of older adults’ CNS to adapt to challenging stimuli both acutely and over time. Further, it demonstrates that BAL, VIS and EP-ST may help to counteract and/or prevent impending age-related declines in neurophysiological integrity, whilst also improving functional ability and targeting mode-specific deficits including reduced muscle strength, impaired balance and poorer proprioceptive acuity. Importantly, the lack of between-group differences observed in these studies in relation to functional improvements and neural adaptations following complex motor training may provide promising opportunities for the personalisation of interventions to target specific deficits in older adults, without compromising the beneficial adaptations within the CNS or to functional ability in general.