Running head: LICI IN YOUNG AND MIDDLE-AGED ADULTS 1 No Difference in Motor Cortical Inhibition Between Young and Middle-Aged Adults: A TMS-EEG Study

5 Introduction . 6 Method . 14 Subjects . 14 Screening . 15 Electromyography . 16 Electroencephalography . 16 Transcranial Magnetic Stimulation . 17 Sham Stimulation . 17 Procedure . 18 Manual Dexterity. 18 Data Analysis . 19 Statistical Analysis . 23 Results . 24 Resting Motor Threshold . 24 Global Mean Field Amplitude. 25 Sham TEP compared to Single-Pulse TEP . 26 Single-Pulse TEP. 28 LICI TEP . 30 Manual Dexterity. 31 Manual Dexterity and LICI Correlates . 33 LICI IN YOUNG AND MIDDLE-AGED ADULTS 4 Discussion . 35 Global Mean Field Amplitude. 35 Comparison of Sham and Single-Pulse TEP . 36 Comparison of Single-Pulse TEP between Young and Middle-Aged Adults . 39 Comparison of LICI TEP between Young and Middle-Aged Adults . 40 Manual Dexterity. 42 Correlations between Manual Dexterity and LICI TEP . 43 Future Research . 44 Conclusion . 45 References . 47 Appendix A Ethics Outright Approval Letter . 59 Appendix B Information Letter to Participants . 60 Appendix C Participant Recruitment Flyer . 63 Appendix D Consent Form . 64 Appendix E Survey Instruments . 65 Appendix F Relevant Statistical Output . 67 Appendix G Project Summary . 77 Thesis character count: 64,998 (10,103 words) LICI IN YOUNG AND MIDDLE-AGED ADULTS 5 General Acknowledgements I would like to thank my primary supervisor, Dr Ann-Maree Vallence, for her constant guidance, support, feedback and encouragement, and my secondary supervisor, Dr Hakuei Fujiyama, for his support and technical expertise. I would like to thank my participants who gave their precious time to contribute towards my research. I would also like to thank Ruby for being a hardworking and supportive lab partner, and Michelle and Jane for teaching me how to use the TMS and EEG equipment. Thank you to my parents for their never-ending encouragement and belief in my abilities, and to my friends for being a welcome distraction at times. Finally, I would like to dedicate this thesis to Patrick – thank you for being my Sam. LICI IN YOUNG AND MIDDLE-AGED ADULTS 6 Abstract It is well established that ageing is associated with a decline in manual dexterity. An important neural process for the control of manual dexterity is motor cortical inhibition, which is the process by which neural activity within the motor cortex is supressed. Reductions in motor cortical inhibition may contribute to the age-related decline inIt is well established that ageing is associated with a decline in manual dexterity. An important neural process for the control of manual dexterity is motor cortical inhibition, which is the process by which neural activity within the motor cortex is supressed. Reductions in motor cortical inhibition may contribute to the age-related decline in manual dexterity. Paired-pulse transcranial magnetic stimulation (TMS) can be used to measure long-interval intracortical inhibition (LICI) in the motor cortex. Previous literature examining differences in LICI between young and older adults have produced conflicting results. In addition, none have included a middle-aged group of participants. The purpose of the current study was to determine whether there are differences in LICI between young and middle-aged adults. An emerging technique that combines TMS with electroencephalography (EEG) was used to measure LICI. In 12 young and 13 middle-aged participants, the TMS-evoked potential (TEP; recorded from EEG) reflected the motor cortical response to sham TMS, single-pulse TMS, and paired-pulse TMS. The TEPs generated by singleand paired-pulse TMS did not differ between young and middle-aged adults. Therefore, there is no evidence from the current study to suggest differences in motor cortical inhibition between young and middle-aged adults. However, these results are speculative as the TEPs generated by sham and single-pulse TMS were highly similar, suggesting that artefacts heavily influenced the TEPs. It is critical that future studies are able to minimise the artefacts during TMSEEG recording, and reliably identify and remove artefacts from the EEG data. LICI IN YOUNG AND MIDDLE-AGED ADULTS 7 No Difference in Motor Cortical Inhibition Between Young and Middle-Aged Adults: A TMS-EEG Study Between 1996 and 2016 the proportion of the Australian population aged 65 years and over increased from 12.0% to 15.3%, and this group is expected to increase more rapidly over the next decade (Australian Bureau of Statistics, 2016). With advanced age comes a decline in motor control and functioning (Seidler et al., 2010). For example, research in motor control has demonstrated that older adults show longer reaction times (Bedard et al., 2002), reduced coordination (Fujiyama, Hinder, Schmidt, Garry, & Summers, 2012), and reduced manual dexterity (Calautti, Serrati, & Baron, 2001) compared to young adults. Coordination and manual dexterity are necessary for the successful execution of everyday tasks such as holding a pen and writing, or tying a shoelace. Therefore, it is not surprising that age-related deficits in motor control impact daily living, leading to reduced independence and a decrease in life satisfaction (Åberg, Sidenvall, Hepworth, O’Reilly, & Lithell, 2005). Evidence-based interventions that improve motor control in ageing populations are critical to minimise the financial burden placed on aged-care resources, and increase overall wellbeing in older adults. In order to develop these interventions, more research is needed to understand the neural mechanisms behind the age-related decline in motor control. A number of brain areas contribute to the planning and execution of movement, including premotor areas, the supplementary motor area, and the cerebellum (Seidler et al., 2010). The primary motor cortex (M1), located in the frontal lobe of the brain along the precentral gyrus, is particularly important for the execution of motor plans that enable dexterous movement (Seidler et al., 2010). Neurons in M1 connect to fibres of the corticospinal tract, which descend through the brain stem and down the spine to activate skeletal muscles (Garret, 2003). Every muscle in the body has a representation in M1, and these representations are arranged somatotopically; for example