Bilateral upper-limb coordination is an important ability for our living independency, since most of our daily tasks, such as lifting a box or using knife and fork, require the simultaneous use of both arms (Waller et al., 2006). However, bilateral coordination decline has been observed in both healthy aging and neurological groups (Pollock et al., 2014; Maes et al., 2017) , which often results in decreased quality of life (Broeks et al., 1999; Franceschini et al., 2010). Therefore, this dissertation sought to understand the characteristics and mechanisms of bilateral coordination and its impairments. The two fundamental bilateral movements in human upper limbs, i.e., in-phase (homologous muscles from bilateral arms activate simultaneously) and anti-phase (different muscle groups from bilateral arms activate simultaneously) movements, have been found to show different characteristics in behavioral and neural measurements (Swinnen and Wenderoth, 2004). Behaviorally, anti-phase movements are found to be performed with lower movement accuracy and higher phase variability between hands compared to in-phase movements (Wuyts et al., 1996; Byblow et al., 2000; Pollok et al., 2007). On the neural level, fMRI studies demonstrated that the left hemisphere shows larger task-related BOLD signal changes compared to the right hemisphere during in-phase movements (Aramaki et al., 2006), while the BOLD signal changes between the two hemispheres are similar during anti-phase movements (Walsh et al., 2008). These results suggest a left-dominated control of in-phase movements. However, a critical limitation in the literature is the lack of causal evidence supporting hemispherical specialization in bilateral coordination. Therefore, it is unclear whether the observed behavioral differences between anti-phase and in-phase movements were truly due to distinct hemispheric control. Another limitation of the literature is the design of existing paradigms. While most of our daily activities involve movements engaging multiple joints at the same time (Keenan et al., 2006; Murphy et al., 2006), previous studies mostly investigated single joint movements (e.g. index finger tapping, forearm pronation-supination). Contrary to single joint movements, bilateral movements engaging multiple joints require not only inter-limb coordination, but also additional intra-limb coordination. Therefore, it is unclear whether the previous findings from single joint movements could be directly applied to multiple joint movements. In this dissertation, we used a bilateral coordination paradigm involving both shoulder and elbow joints to investigate the neural mechanisms behind bilateral coordination and its decline. We designed three studies focusing on 1) the differences between bilateral in-phase and anti-phase movements from a human motion perspective, 2) how aging affects different bilateral coordination patterns and its neural correlates, as well as 3) how lesioned hemisphere affects bilateral coordination impairments and whether distinct rehabilitation treatments are needed after a left or right hemispheric stroke. In Study 1, we examined the two basic bilateral coordination modes, in-phase and anti-phase movements, in healthy young right-handed participants. We used a bilateral circle drawing task involving both shoulder and elbow joints. During the movements, we measured participants’ hand positions with high temporal and spatial precision, and developed intra-limb and inter-limb measures to differentiate movement characteristics during the two basic movement modes. For intra-limb coordination, we quantified trajectory variability of each hand during the movements. For inter-limb coordination, we computed the phase synchronization between hands. We found that intra-limb coordination was worse in the non-dominant hand during anti-phase compared to in-phase movements. In contrast, intra-limb coordination in the dominant hand did not differ between anti-phase and in-phase movements. Second, participants showed worse inter-limb synchronization during anti-phase compared to in-phase movements. Moreover, we examined the hand acceleration profile of both hands, and found that participants’ bilateral hands accelerated and decelerated in an in-phase manner during in-phase movements. In contrast, the acceleration and deceleration of the two hands were unrelated during anti-phase movements. These inter-limb acceleration profiles support the idea of differential neural mechanisms behind bilateral anti-phase and in-phase movements: during in-phase movements, the hands are governed by a common neural generator, while during anti-phase movements, the two hands are controlled by both hemispheres more independently. Taken together, Study 1 showed that the current experimental setup is able to differentiate the performance between bilateral in-phase and anti-phase movements engaging multiple joints. Therefore, we used the same paradigm combined with electroencephalography (EEG) to examine the presumed decline of bilateral coordination in aging. In Study 2, we investigated the effect of aging on the two basic bilateral movement modes. We used intra- and inter-limb measures as the behavioral measures, and EEG as a neural measure. Behaviorally, we found that older adults only showed significant impairments in anti-phase movements, but not in-phase movements, compared to young adults. On the neural level, we found that older adults showed different neural responses during anti-phase and in-phase movements compared to young adults. Specifically, during in-phase movements, young adults showed a more pronounced decrease of alpha power (8-12 Hz) over the left compared to the right hemisphere, while older adults showed similar levels of alpha power decrease over both hemispheres. Furthermore, in the older adults, we found a marginal correlation between the change in alpha power over the right hemisphere and the behavioral performance, which indicated a compensatory brain response. As for the anti-phase movements, we found that participants with stronger directional inter-hemispheric connectivity in the beta band (15-25 Hz) showed worse behavioral performance, and this effect was more pronounced in the older adults. This result implies that a balanced inter-hemispheric contribution is essential for executing a successful anti-phase movement. Our findings therefore show that the two hemispheres are differentially involved in the two basic bilateral coordination modes. These different neural characteristics may explain the distinct decline patterns of in-phase and anti-phase movements in older adults. However, causal evidence to support hemispherical specialization is needed to confirm our findings. Therefore, we conducted Study 3, where we used stroke as a lesion model to examine the influence of the lesioned hemisphere on bilateral coordination. In Study 3, we examined the bilateral coordination ability in patients with left (LHS) and right hemispheric stroke (RHS), as well as healthy controls. Given that healthy young participants show a left-dominant control in in-phase movements in Study 2 and in the previous literature (Aramaki et al., 2006; Maki et al., 2008), we expected that LHS patients would display a more pronounced impairment of in-phase movements compared to RHS patients. In contrast, since anti-phase movements require a more balanced inter-hemispheric contribution as shown in Study 2, and RHS patients show larger inter-hemispheric inhibition compared to healthy participants and LHS patients (Lewis and Perreault, 2007b), we expected that RHS patients would show more impairment in anti-phase movements compared to LHS patients. As predicted, we found that patients with RHS patients exhibited greater impairment during anti-phase movements (both intra- and inter-limb parameters) and LHS patients showed greater impairment during in-phase movements (intra-limb parameters only). Though LHS patients did not show greater impairment in inter-limb coordination during in-phase movements compared to RHS patients, our regression analysis revealed that only LHS patients swapped hand dominance during the task. We interpreted this result as a compensatory mechanism whereby bilateral in-phase movements in the LHS group switched from a left-dominated cortical control to a right-dominated cortical control. Our findings not only provide causal evidence for hemispheric specialization in bilateral movement coordination, but also characterize the differential impairments in bilateral coordination after a left or right hemispheric stroke. Taken together, this dissertation highlighted differential neural control processes involved in bilateral in-phase and anti-phase movements, and demonstrated how these distinct mechanisms lead to impaired bilateral coordination in aging and stroke. The present results could therefore advance the development of therapeutic strategies that seek to counteract bilateral coordination decline, such as differential treatment for patients with left and right hemispheric lesions, or the use of noninvasive brain stimulation at a target hemisphere.:List of abbreviations List of figures List of tables Chapter 1. General introduction 1.1. Introduction 1.2. Bilateral coordination in human upper extremities 1.3. Age-related motor decline 1.4. Stroke-induced motor impairments Chapter 2. Rationale of the Dissertation Chapter 3. Study I: Human motion characteristics during bilateral in-phase and anti-phase movements 3.1. Introduction 3.2. Materials and methods 3.3. Results 3.4. Discussion 3.5. Conclusion Chapter 4. Study II: The effect of aging on bilateral coordination 49 4.1. Introduction 4.2. Materials and methods 4.3. Results 4.4. Discussion 4.5. Conclusion Chapter 5. Study III: Effects of lesioned side on bilateral coordination after strokes 5.1. Introduction 5.2. Materials and methods 5.3. Results 5.4. Discussion 5.5. Conclusion Chapter 6. General discussion 6.1. Summary of research 6.2. Contributions and clinical implications 6.3. Outlook for future research Chapter 7. Summary of the dissertation References Appendix Appendix 1. Supplementary information for study 1 Appendix 2. Supplementary information for study 2 Appendix 3. Supplementary information for study 3 Appendix 4. Declaration of authenticity