The utility of new motor control paradigms in multiple sclerosis: an investigation of motor overflow and reciprocal aiming

Abstract

Multiple Sclerosis (MS) is a neurological disease marked by widespread inflammation, demyelination and neurodegeneration in both white and gray matter structures of the brain and spinal cord. The widespread networks which mediate motor control are commonly damaged in MS, with up to 80% of MS patients experiencing motor symptoms such as muscle weakness, poor fine motor control and gait abnormalities. Despite the high prevalence of motor symptoms in MS, commonly used assessments overlook subtle, yet potentially important, aspects of motor control, such as the presence of involuntary movements, movement kinematics, movement planning, and online control of movement. This thesis investigates motor overflow and reciprocal aiming in MS to provide new insights into these subtle and unobservable aspects of MS-related motor dysfunction. This research provides preliminary data which may lead to the development of new assessments of motor symptoms in MS which are not only capable of capturing a broad range of motor symptoms in; but that may be sensitive to neuropathological changes, disease progression and therapeutic intervention. Motor overflow refers to involuntary movement that can accompany production of voluntary movement. The neurophysiological origins of motor overflow are not fully understood though it is evident that the corpus callosum (CC) is an important structure in the production and suppression of this phenomenon. Being the largest white matter tract in the central nervous system, the CC is commonly damaged in MS. Therefore it was considered conceivable that overflow may be exacerbated in MS and measurement of overflow might provide an index of MS-related CC pathology. Reciprocal aiming involves a two-stage process: 1) an initial planned ballistic movement which brings the limb close to the target, and 2) accurate movement of the limb to the target. These stages of movement require functional movement planning and online control respectively. By objectively measuring reciprocal aiming, unobservable aspects of movement planning, online control and movement accuracy can be measured. Studies 1 and 2 (Chapters 4 and 5) of this thesis used a motor overflow task to characterise voluntary force control and involuntary motor overflow in MS and control participants. Study 1 (Chapter 4) found that motor overflow levels did not differ between MS and control participants. However motor overflow was related to disease progression. These findings suggest that motor overflow may be exacerbated in more advanced stages of the disease. Motor overflow did not correlate with MRI measures of CC damage suggesting that structures other than the CC play an important role in its production and suppression. Study 2 (Chapter 5) demonstrated that motor overflow was significantly exacerbated in MS participants compared with controls which is likely a consequence of the inclusion of an MS sample with more advanced disease compared to the sample in Study 1 (Chapter 4). Similarly to Study 1 (Chapter 4), overflow was related to disease progression. The study also found that voluntary motor stability was significantly compromised in MS and poorer motor stability correlated with disease progression. Incorporating a concurrent cognitive test in conjunction with the overflow task did not differentially influence motor overflow or motor stability in MS compared to controls. These findings suggest that while exacerbated motor overflow and poorer motor stability may be features of MS, concurrent tasking is preserved. Studies 3 and 4 (Chapters 6 and 7) used a reciprocal aiming task to characterise movement planning, online control and accuracy in MS and control participants. Study 3 (Chapter 6) found that MS participants’ movements were equally as accurate as controls, however they displayed significant deficits in movement planning and online control of movement. MS participants were also disproportionately affected by changes in task difficulty compared with controls. Study 4 (Chapter 7) incorporated a concurrent cognitive task with the reciprocal aiming task. As found in Study 2 (Chapter 5), MS participants were not differentially affected by a concurrent task compared with controls; confirming the preserved dual tasking ability observed in these individuals. Several important conclusions can be drawn from this research. Firstly, it is clear that MS patients experience a range of motor symptoms over and above those that are clinically evident and commonly measured using traditional motor assessments. These symptoms affect both voluntary (movement planning, accuracy, online control, stability) and involuntary (motor overflow) motor functions. However these deficits do not impact on their ability to perform motor and cognitive tasks concurrently. Secondly, the motor overflow task did not consistently differentiate MS and control participants and was not reflective of CC damage. Therefore, with current data, the motor overflow task is unlikely to possess clinical utility in the detection of early and subtle changes in MS. Thirdly, the Fitts’ law reciprocal aiming task is capable of detecting subtle changes across a range of movement variables. Given its ability to capture these subtle changes, and that it is quick and easy to administer, it is proposed that the Fitts’ law reciprocal aiming task possesses clinical utility. The research presented in this thesis provides important preliminary data for the development of more sensitive and objective motor assessments in MS. Such assessments have the potential to provide supplementary measures of disease status, progression, and efficacy of novel treatments, particularly in proof of concept studies