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Bipedal Hopping Timed with a Metronome to Detect Impairments In BIPEDAL HOPPING TIMED WITH A METRONOME TO DETECT IMPAIRMENTS IN ANTICIPATORY MOTOR CONTROL IN PEOPLE WITH MILD MULTIPLE SCLEROSIS by © Megan C. Kirkland, A Thesis submitted to the School of Graduate Studies in partial fulfillment of the requirements for the degree of MSc. Med. (Clinical Epidemiology) Faculty of Medicine Memorial University of Newfoundland October 2017 St. John’s Newfoundland and Labrador 1 Abstract Background: People with mild multiple sclerosis (MS) often report difficulty in balance and cognition but display no measurable deficits on many clinical assessments. We examined whether hopping to a metronome beat has the potential to detect anticipatory motor control deficits among people with mild MS (Expanded Disease Severity Score ≤ 3.5). Methods: Participants with MS (n=13), matched controls (n=9), and elderly subjects (n=13) completed tests of cognition (Montreal Cognitive Assessment (MoCA)) and motor performance (Timed 25 Foot Walk Test (T25FWT)). Participants performed two bipedal hopping tasks: at 40 beats/minute (bpm) and 60-bpm in random order. Hop characteristics (length, symmetry, variability) and delay from the metronome beat were extracted from an instrumented walkway and compared between groups using a one-way ANOVA. Results: The MS group became more delayed from the metronome beat over time whereas elderly subjects tended to hop closer to the beat during 40-bpm (F=3.58, p=0.04). Delay of the first hop during 60-bpm predicted cognition in people with MS (R=0.55, β=4.64 (SD 4.63), F=4.85, p=0.05) but not among control (R=0.07, p=0.86) or elderly subjects (R=0.17, p=0.57). In terms of hopping characteristics, people with MS performed similarly to the matched controls during 60-bpm, but shifted towards the elderly subjects’ ability during 40-bpm. Conclusions: This new timed hopping test may be able to detect both physical ability and feed-forward anticipatory control impairments in people with mild MS. Hopping at a frequency of 40-bpm seemed more challenging. Two aspects of anticipatory motor control can be measured: response time to the first metronome cue and the ability to adapt and anticipate the beat over time. i Acknowledgements I would like to acknowledge my supervisor, Dr. Michelle Ploughman, who has taught me all I know about research and has guided me through my success in this degree. Also, I acknowledge the members of the Recovery & Performance Laboratory for their support and guidance throughout my project. This thesis would not be possible without the continued support of laboratory staff and fellow researchers. This lab environment has truly made this Master’s experience very special. I would also like to thank the members of my committee, Dr. Craig Moore, Dr. Kathleen Hodgkinson and Dr. Shabnam Asghari, for taking the time to review my thesis and provide valuable feedback. I would also like to acknowledge TPMI NL SUPPORT for providing me with funding that enabled me to dedicate full-time to my studies. This agency also provided me with a travel award to present my thesis at an international conference. I would also like to thank the Multiple Sclerosis Society of Canada for supporting my attendance at various conferences and the opportunity to attend endMS Summer Schools. These learning experiences are ones I will hold for a lifetime and am extremely thankful for the support that made these opportunities possible. Lastly, I would like to thank my friends and family, who have supported me throughout this journey. I would like to give a special appreciation to my parents and Darren Hookey, who have stood by my side and been my ultimate supporters throughout this degree. ii Table of Contents ABSTRACT ................................................................................................................................. I ACKNOWLEDGEMENTS ............................................................................................................ II TABLE OF CONTENTS ............................................................................................................... III LIST OF TABLES ...................................................................................................................... VII LIST OF FIGURES ................................................................................................................... VIII LIST OF ABBREVIATIONS .......................................................................................................... IX CHAPTER 1: INTRODUCTION AND LITERATURE REVIEW ............................................................ 1 1.1 GENERAL INTRODUCTION ............................................................................................... 1 1.2 OVERVIEW OF MULTIPLE SCLEROSIS ............................................................................... 3 1.2.1 Epidemiology ............................................................................................................... 3 1.2.2 Diagnosis and Disease Course ..................................................................................... 4 1.2.3 Lesions and Neurodegeneration .................................................................................. 7 1.2.3.1 White Matter Lesions .......................................................................................................................... 7 1.2.3.2 Grey Matter Lesions ............................................................................................................................. 8 1.2.3.3 Axonal Degeneration ......................................................................................................................... 10 1.2.4 MS Similarities to Senescence .................................................................................... 11 1.2.5 Lesion Location and Impairment ................................................................................ 13 1.3 MOTOR IMPAIRMENT .................................................................................................... 15 1.3.1 Muscle Weakness ...................................................................................................... 15 1.3.2 Balance ...................................................................................................................... 17 1.3.3 Coordination .............................................................................................................. 18 1.3.4 Spasticity .................................................................................................................... 19 1.4 REHABILITATION AND MEASUREMENT ......................................................................... 21 iii 1.4.1 Rehabilitation Goals and Importance of Measurement Tools ................................... 21 1.4.2 Expanded Disability Status Scale ............................................................................... 22 1.4.3 Timed 25-Foot Walk Test ........................................................................................... 23 1.4.4 Need for Challenging Motor Assessment ................................................................... 24 1.5 BIPEDAL HOPPING ......................................................................................................... 24 1.5.1 Neuromuscular Control of Hopping ........................................................................... 24 1.5.2 Biomechanical Phases of Hopping ............................................................................. 25 1.5.3 Hopping as an Assessment Tool ................................................................................ 27 1.5.4 Effect of Age on Hopping ........................................................................................... 28 1.5.5 Hopping in MS ........................................................................................................... 29 1.6 SENSORIMOTOR SYSTEM ............................................................................................... 30 1.6.1 Role of Cerebellum in the Sensorimotor System ........................................................ 30 1.6.2 Cerebellar Impairment in MS ..................................................................................... 31 1.6.3 Role of the Basal Ganglia in the Sensorimotor System .............................................. 32 1.6.4 Basal Ganglia are Affected by MS .............................................................................. 32 1.6.5 Need for Early Measurement of Sensory-Motor Impairment .................................... 33 1.7 METRONOME ................................................................................................................ 34 1.7.1 Rhythmic Timing ........................................................................................................ 34 1.7.1.1 Internally Triggered Timing ................................................................................................................ 34 1.7.1.2 Externally Triggered Timing ............................................................................................................... 36 1.7.2 Perceiving an Externally Triggered Beat .................................................................... 37 1.7.3 Rhythmic Timing ........................................................................................................ 38 1.7.4 Timing Optimization .................................................................................................. 39 1.7.5 Does Rhythm Frequency Matter? .............................................................................
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