Susan J. Harkema

Retraining the injured spinal cord.

The present review presents a series of concepts that may be useful in developing rehabilitative strategies to enhance recovery of posture and locomotion following spinal cord injury. First, the loss of supraspinal input results in a marked change in the functional efficacy of the remaining synapses and neurons of intraspinal and peripheral afferent (dorsal root ganglion) origin. Second, following a complete transection the lumbrosacral spinal cord can recover greater levels of motor performance if it has been exposed to the afferent and intraspinal activation patterns that are associated with standing and stepping. Third, the spinal cord can more readily reacquire the ability to stand and step following spinal cord transection with repetitive exposure to standing and stepping. Fourth, robotic assistive devices can be used to guide the kinematics of the limbs and thus expose the spinal cord to the new normal activity patterns associated with a particular motor task following spinal cord injury. In addition, such robotic assistive devices can provide immediate quantification of the limb kinematics. Fifth, the behavioural and physiological effects of spinal cord transection are reflected in adaptations in most, if not all, neurotransmitter systems in the lumbosacral spinal cord. Evidence is presented that both the GABAergic and glycinergic inhibitory systems are up‐regulated following complete spinal cord transection and that step training results in some aspects of these transmitter systems being down‐regulated towards control levels. These concepts and observations demonstrate that (a) the spinal cord can interpret complex afferent information and generate the appropriate motor task; and (b) motor ability can be defined to a large degree by training.

Clonus after human spinal cord injury cannot be attributed solely to recurrent muscle-tendon stretch

Clonus, presented behaviorally as rhythmic distal joint oscillation, is a common pathology that occurs secondary to spinal cord injury (SCI) and other neurological disabilities. There are two predominant theories as to the underlying mechanism of clonus. The prevailing one is that clonus results from recurrent activation of stretch reflexes. An alternative hypothesis is that clonus results from the action of a central oscillator. We present evidence that the mechanism underlying clonus in individuals with SCI is not solely related to muscle stretch. We studied electromyography (EMG) of the soleus (SOL), medial gastrocnemius (MG), tibialis anterior (TA), medial and lateral hamstrings, vastus medialis, vastus lateralis, and rectus femoris from subjects with clinically complete and clinically incomplete SCI during stretch-induced ankle clonus, stepping, and non-weight-bearing standing. Clonic EMG of the SOL, MG, and TA occurred synchronously and were not consistently related to muscle-tendon stretch in any of the conditions studied. Further, EMG activity during stretch-induced ankle clonus, stepping, and non-weight-bearing standing had similar burst frequency, burst duration, silent period duration, and coactivation among muscles, indicating that clonic EMG patterns occurred over a wide range of kinematic and kinetic conditions, and thus proprioceptive inputs. These results suggest that the repetitive clonic bursts could not be attributable solely to immediate afferent feedback such as recurrent muscle stretch. However, these results support the theory that the interaction of central mechanisms and peripheral events may be responsible for clonus.

Modulation of multisegmental monosynaptic responses in a variety of leg muscles during walking and running in humans

Motor responses evoked by stimulating the spinal cord percutaneously between the T11 and T12 spinous processes were studied in eight human subjects during walking and running. Stimulation elicited responses bilaterally in the biceps femoris, vastus lateralis, rectus femoris, medial gastrocnemius, soleus, tibialis anterior, extensor digitorum brevis and flexor digitorum brevis. The evoked responses were consistent with activation of Ia afferent fibres through monosynaptic neural circuits since they were inhibited when a prior stimulus was given and during tendon vibration. Furthermore, the soleus motor responses were inhibited during the swing phase of walking as observed for the soleus H‐reflex elicited by tibial nerve stimulation. Due to the anatomical site and the fibre composition of the peripheral nerves it is difficult to elicit H‐reflex in leg muscles other than the soleus, especially during movement. In turn, the multisegmental monosynaptic responses (MMR) technique provides the opportunity to study modulation of monosynaptic reflexes for multiple muscles simultaneously. Phase‐dependent modulation of the MMR amplitude throughout the duration of the gait cycle period was observed in all muscles studied. The MMR amplitude was large when the muscle was activated whereas it was generally reduced, or even suppressed, when the muscle was quiescent. However, during running, there was a systematic anticipatory increase in the amplitude of the MMR at the end of swing in all proximal and distal extensor muscles. The present findings therefore suggest that there is a general control scheme by which the transmission in the monosynaptic neural circuits is modulated in all leg muscles during stepping so as to meet the requirement of the motor task.

A robotic tool for studying locomotor adaptation and rehabilitation

This paper describes a robotic device designed to measure and manipulate human stepping on a treadmill. The device makes use of a parallel mechanism and a moving coil type linear motor to achieve good backdriveability and force generation capability. We demonstrate that the device does not substantially impede stepping when attached passively to a subject, and can induce motor adaptation and after-effects in a simple force-field experiment.

An assistive robotic device that can synchronize to the pelvic motion during human gait training

We are developing a robotic device, PAM (pelvic assist manipulator), that assists the pelvic motion during human gait training on a treadmill. PAM allows naturalistic motion of pelvis actuated by six pneumatic cylinders, which, combined with a nonlinear force-tracking controller, provide backdrivability and large force output at a relatively low cost. PAM can act as a teach-and-replay device with a PD position controller driving the pelvis onto the reference trajectory specified with or without the help of therapists. During initial experiments with unimpaired subjects, we encountered a problem in which the subjects had difficulty synchronizing their movements with the gait pattern reproduced by PAM, even though that gait pattern had been sampled from the subjects themselves. We introduced footswitches to detect the gait timing and developed a feedback control algorithm that adjusts the play-back speed of the gait pattern in real-time. The feedback algorithm is presented, along with data that shows the effectiveness of the algorithm in synchronizing the robotic assistance during stepping by unimpaired subjects, even when the subjects change their step size and period.

How the science and engineering of spaceflight contribute to understanding the plasticity of spinal cord injury

Space programs support experimental investigations related to the unique environment of space and to the technological developments from many disciplines of both science and engineering that contribute to space studies. Furthermore, interactions between scientists, engineers and administrators, that are necessary for the success of any science mission in space, promote interdiscipline communication, understanding and interests which extend well beyond a specific mission. NASA-catalyzed collaborations have benefited the spinal cord rehabilitation program at UCLA in fundamental science and in the application of expertise and technologies originally developed for the space program. Examples of these benefits include: (1) better understanding of the role of load in maintaining healthy muscle and motor function, resulting in a spinal cord injury (SCI) rehabilitation program based on muscle/limb loading; (2) investigation of a potentially novel growth factor affected by spaceflight which may help regulate muscle mass; (3) development of implantable sensors, electronics and software to monitor and analyze long-term muscle activity in unrestrained subjects; (4) development of hardware to assist therapies applied to SCI patients; and (5) development of computer models to simulate stepping which will be used to investigate the effects of neurological deficits (muscle weakness or inappropriate activation) and to evaluate therapies to correct these deficiencies.

Quantification of Therapists' Manual Assistance on the Leg during Treadmill Gait Training with Partial Body-Weight Support after Spinal Cord Injury

We are studying the forces applied by therapists when assisting on the legs of patients with spinal cord injury (SCI) during body-weight supported treadmill training (BWSTT). This paper presents results from three experiments with three patients and six different therapists. We attached a sensorized orthosis to one of the legs of the patients and measured the forces exerted by the therapists when assisting on that leg through the orthosis. We also measured the kinematics of the shank. The hips and opposite leg were assisted by two other therapists as usual. We found a high repeatability across steps for the forces applied by each therapist. Better-skilled therapists elicited significantly better leg extension in stance phase by exerting significantly larger horizontal forces on the knee during stance. Better-skilled therapists also elicited better toe clearance during initial-to-mid swing, with fewer or no episodes of toe dragging. This better toe clearance was not generally correlated with larger therapist push-up forces at the ankle. We did find, however, that better toe clearance in swing was correlated with better extension of the same leg in stance, suggesting that a normative leg extension in stance contributed to better muscle activity of the same leg in swing. These results provide insight into therapist-assisted gait training, which may be useful for optimizing robotic gait-training devices.