Training-induced changes in cortical excitability may play an important role in rehabilitation of gait ability in patients with neurological disorders. In this study, we investigated the effect of a 32-min period of motor skill, non-skill and passive training involving the ankle muscles on leg motor cortical excitability in healthy humans. Transcranial magnetic stimulation (TMS) at a range of intensities was applied to obtain a recruitment curve of the motor evoked potentials (MEPs) in the tibialis anterior (TA) muscle before and after training. We also explored the effect of training on inhibitory and facilitatory cortical circuits by using a paired-pulse TMS technique at intervals of 2.5 ms (short-interval intracortical inhibition, SICI) and 8 ms (intracortical facilitation, ICF). During motor skill training, subjects were instructed to make a cursor follow a series of target lines on a computer screen by performing voluntary ankle dorsi- and plantarflexion movements. Non-skill and passive training consisted of repeated voluntary and assisted dorsi- and plantarflexion movements, respectively. Recruitment curves increased significantly after 32 min of motor skill training but not after non-skill and passive training, suggesting that only skill motor training increases motor cortical excitability. Motor skill training was not accompanied by any changes in the recruitment curves of TA MEPs evoked by transcranial electrical stimulation, suggesting that the increased MEPs to TMS was likely caused by changes in excitability at a cortical site. SICI was decreased after 32 min of motor skill training but no changes were observed in ICF. We conclude that similar plastic changes as have previously been reported for the hand motor following motor skill training may also be observed for the leg motor area. The observed plastic changes appeared to be related to the degree of difficulty in the motor task, and may be of relevance for rehabilitation of gait disorders.

Summary The corticospinal tract is an important target for motor recovery after spinal cord injury (SCI) in animals and humans [1-5]. Voluntary motor output depends on the efficacy of synapses between corticospinal axons and spinal motoneurons, which can be modulated by the precise timing of neuronal spikes [6-8]. Using noninvasive techniques, we developed tailored protocols for precise timing of the arrival of descending and peripheral volleys at corticospinal-motoneuronal synapses of an intrinsic finger muscle in humans with chronic incomplete SCI. We found that arrival of presyn-aptic volleys prior to motoneuron discharge enhanced corticospinal transmission and hand voluntary motor output. The reverse order of volley arrival and sham stimulation did not affect or decreased voluntary motor output and electrophysiological outcomes. These findings are the first demonstration that spike timing-dependent plasticity of residual corticospinal-motoneuronal synapses provides a mechanism to improve motor function after SCI. Modulation of residual corticospinal-motoneuronal synapses may present a novel therapeutic target for enhancing voluntary motor output in motor disorders affecting the corticospinal tract.

The corticospinal tract (CST) is a major descending pathway contributing to the control of voluntary movement in mammals. During the last decades anatomical and electrophysiological studies have demonstrated significant reorganization in the CST after spinal cord injury (SCI) in animals and humans. In animal models of SCI, anatomical evidence showed corticospinal sprouts rostral and caudal to the lesion and their integration into intraspinal axonal circuits. Electrophysiological data suggested that indirect connections from the primary motor cortex to forelimb motoneurons, via brainstem nuclei and spinal cord interneurons, or direct connections from slow uninjured corticospinal axons, might contribute to the control of movement after a CST injury. In humans with SCI, post mortem spinal cord tissue revealed anatomical changes in the CST some of which were similar but others markedly different from those found in animal models of SCI. Human electrophysiological studies have provided ample evidence for corticospinal reorganization after SCI that may contribute to functional recovery. Together these studies have revealed a large plastic capacity of the CST after SCI. There is also a limited understanding of the relationship between anatomical and electrophysiological changes in the CST and control of movement after SCI. Increasing our knowledge of the role of CST plasticity in functional restoration after SCI may support the development of more effective repair strategies. Martin Oudega received his PhD from the University of Leiden in The Netherlands. Currently, he is faculty at the Departments of Physical Medicine and Rehabilitation, Neurobiology and Bioengineering at the University of Pittsburgh, USA. He directs the Spinal Cord Injury and Repair Laboratory and studies the efficacy of cellular and non-cellular transplants, alone or in combination with axon growth-supporting interventions, to elicit anatomical and/or functional restoration after spinal cord injury. He also investigates which genes are crucial for successful axon regeneration and functional restoration in zebrafish with spinal cord injury. The overall goal of his studies is to develop spinal cord repair strategies for clinical translation. Monica A. Perez received her PhD from the University of Miami, FL, USA. She is a faculty member at the Departments of Physical Medicine and Rehabilitation and Physical Therapy and a member of the Systems Neuroscience Institute at the University of Pittsburgh, USA. Her research examines how the brain and spinal cord contribute to the control of movements in healthy humans and in individuals with spinal cord injury. This theme is mainly investigated from a neurophysiological point of view, using a combination of transcranial magnetic and electrical stimulation, and peripheral nerve stimulation techniques. The overall goal of her studies is to develop strategies that can be used to maximize function of partially paralysed muscles after spinal cord injury.