Using a multimodal neuroimaging approach to understand the impacts of ageing on implicit motor sequence learning
Authors:   , Leuk Jessie Siew Pin 
Published: February 2025

The ability to implicitly learn a skill is fundamental for human behaviour and daily functioning, yet this ability deteriorates with age. This thesis aims to elucidate the underlying neural processes affected by ageing that contribute to the declines in implicit motor sequence learning (IMSL). Two core objectives were addressed: 1) Assess the age-related changes in intrinsic readiness for learning through resting-state functional connectivity (RS-FC) of key cognitive-motor brain regions (left and right prefrontal cortices [PFC], premotor areas [PMA] and primary motor areas [M1]) in Study 1 (Chapter 3) and pre-movement corticospinal excitability and inhibition in Study 2 (Chapter 4); 2) Elucidate the roles of supplementary motor area (SMA) and M1 in IMSL via a concurrent transcranial direct current stimulation (tDCS)- functional near-infrared spectroscopy (fNIRS) approach. A meta-analysis was first presented in Chapter 5 to justify the rationale and methodologies used in Study 3 (Chapter 6). Participants from two age groups were recruited for each study: young (aged 21-40) and older adults (aged 65-80). IMSL was assessed via a serial reaction time task (SRTT), which requires participants to repeatedly perform a sequence of finger movements without being aware that a sequence is present. The inclusion of random sequences in between the embedded sequences enables the dissociation between general visuomotor learning (ML) and sequence-specific learning (SSL), which the latter often compromised in older adults. Study 1 utilised fNIRS to investigate whether RS-FC could predict subsequent SRTT performance. This study revealed an overall weakened RS-FC in the older adults, specifically in the connectivity between PFCLeft, PMARight and M1Right when predicting SSL. Study 2 utilised Transcranial Magnetic Stimulation (TMS) to assess neural dynamics of the motor network just before a movement is made. Our results indicated that older adults showed a decreased pre-movement excitatory response alongside potential adaptations in cortical inhibition compared to younger adults. These differences might contribute to the absence in SSL in older adults. Study 3 sought to utilise the above findings on the need to enhance the ageing brainâ€™s readiness for IMSL. A concurrent tDCS- fNIRS approach was employed to induce changes in the SMA and M1, to clarify their contributions during SRTT. Stimulating these areas did not improve SRTT performance but yielded distinct neural responses between the age groups. Specifically in older adults, there were changes in PMALeft and PMARight activity post-M1-stimulation. In younger adults, functional connectivity within the right hemisphere and PFCLeft - PFCRight were enhanced during SMA stimulation. These results highlighted the complexity of neural plasticity across different age groups and suggested that SMA as a promising target for future research and intervention in IMSL. Overall, weakened interhemispheric connections within the PFC, PMA and M1, as well as altered pre-movement neural dynamics were associated with a decline in IMSL ability in older adults. While tDCS targeting the SMA and M1 elicited age-dependent neural responses, the SMA emerged as a promising stimulation site for enhancing cognitive-motor integration necessary for SSL. However, this premise is contingent upon the development of tailored neuromodulatory interventions that considers individual differences in neural profiles.