DISS. ETH No. 22056 Gait Control and Locomotor Recovery after Spinal Cord Injury A thesis submitted to attain the degree of DOCTOR OF SCIENCES of ETH ZURICH (Dr. sc. ETH Zürich) presented by Lea Awai MSc ETH HMS born on 2nd July 1984 Citizen of Untervaz (GR) and Japan accepted on the recommendations of Prof. Dr. Martin E. Schwab Prof. Dr. Armin Curt Prof. Dr. Grégoire Courtine ~ 2014 ~ Contents Summary ................................................................................................................................................ 1 Zusammenfassung .................................................................................................................................. 4 General Introduction ............................................................................................................................. 7 Aims ..................................................................................................................................................... 10 Study 1 Intralimb coordination as a sensitive indicator of motor-control impairment after spinal cord injury ............................................................................................................................................ 11 1.1 Abstract .................................................................................................................................... 12 1.2 Introduction ......................................................................................................................... 13 1.3 Materials and methods ......................................................................................................... 15 1.4 Results .................................................................................................................................. 18 1.5 Discussion ............................................................................................................................. 23 1.6 Conclusion ............................................................................................................................ 26 Study 2 Domains of neural control of walking in human spinal cord injury ....................................... 27 2.1 Abstract ................................................................................................................................ 28 2.2 Introduction ......................................................................................................................... 29 2.3 Materials and methods ......................................................................................................... 30 2.4 Results .................................................................................................................................. 34 2.5 Discussion ............................................................................................................................. 42 2.6 Conclusion ............................................................................................................................ 46 Study 3 Locomotor recovery in spinal cord injury – why do patients walk faster? ............................ 47 3.1 Abstract ................................................................................................................................ 48 3.2 Introduction ......................................................................................................................... 49 3.3 Materials and methods ......................................................................................................... 51 3.4 Results .................................................................................................................................. 55 3.5 Discussion ............................................................................................................................. 61 3.6 Conclusion ............................................................................................................................ 64 Study 4 Extensive plasticity of the human spinal cord ........................................................................ 65 4.1 Abstract ................................................................................................................................ 66 4.2 Introduction ......................................................................................................................... 67 4.3 Materials and methods ......................................................................................................... 69 4.4 Results .................................................................................................................................. 73 4.5 Discussion ............................................................................................................................. 80 4.6 Conclusion ............................................................................................................................ 84 Appendix Corticospinal tract plasticity after spinal cord injury supports greater recovery in humans and monkeys than rats ......................................................................................................................... 85 A.1 Abstract ................................................................................................................................ 86 A.2 Introduction ......................................................................................................................... 87 A.3 Materials and methods ......................................................................................................... 89 A.4 Results .................................................................................................................................. 99 A.5 Discussion ........................................................................................................................... 118 A.6 Conclusion .......................................................................................................................... 121 General Discussion ............................................................................................................................. 123 Walking pattern and neural control of walking in iSCI ............................................................... 123 Plasticity after iSCI ........................................................................................................................ 125 From bench to bedside ................................................................................................................... 126 From bedside to activity ................................................................................................................ 127 Limitations ..................................................................................................................................... 128 Conclusion ...................................................................................................................................... 128 Outlook .............................................................................................................................................. 129 Neural basis of locomotor control ................................................................................................. 129 Sensory-motor integration ............................................................................................................. 130 From bench to bedside to activity ................................................................................................. 131 References .......................................................................................................................................... 133 Glossary .............................................................................................................................................. 150 Curriculum Vitae ............................................................................................................................... 153 Publications ........................................................................................................................................ 157 Acknowledgements ........................................................................................................................... 159 Summary The gait of patients with an incomplete spinal cord injury (iSCI) has been studied previously. The most widely examined parameters to characterize iSCI gait are walking speed and time-distance measures (e.g., step length, step frequency, gait-cycle phases). In a clinical setting, the functional recovery of iSCI patients is routinely captured by specific outcome measures such as the 10-meter walk test (10mWT), the 6-minute walk test (6minWT) or the walking index for spinal cord injury (WISCI), which has been specifically established for this particular group of patients to score their walking ability. These measures are useful to monitor gross motor function and recovery during rehabilitation, but lack the ability to elucidate underlying mechanisms of gait alterations and recovery or subtle changes in locomotor pattern. In order to be able to appreciate the injury-induced deficits in locomotor control and to capture changes in motor function that may not be visible to the naked eye a sensitive and comprehensive tool is of need. The easiest way of assessing walking capacity is to collect data of walking speed