Tomoko Kitago

Motor learning principles for neurorehabilitation

Neurorehabilitation is based on the assumption that motor learning contributes to motor recovery after injury. However, little is known about how learning itself is affected by brain injury, how learning mechanisms interact with spontaneous biological recovery, and how best to incorporate learning principles into rehabilitation training protocols. Here we distinguish between two types of motor learning, adaptation and skill acquisition, and discuss how they relate to neurorehabilitation. Functional recovery can occur through resolution of impairment (reacquisition of premorbid movement patterns) and through compensation (use of alternative movements or effectors to accomplish the same goal); both these forms of recovery respond to training protocols. The emphasis in current neurorehabilitation practice is on the rapid establishment of independence in activities of daily living through compensatory strategies, rather than on the reduction of impairment. Animal models, however, show that after focal ischemic damage there is a brief, approximately 3-4-week, window of heightened plasticity, which in combination with training protocols leads to large gains in motor function. Analogously, almost all recovery from impairment in humans occurs in the first 3 months after stroke, which suggests that targeting impairment in this time-window with intense motor learning protocols could lead to gains in function that are comparable in terms of effect size to those seen in animal models.

Improvement After Constraint-Induced Movement Therapy Recovery of Normal Motor Control or Task-Specific Compensation?

Background. Constraint-induced movement therapy (CIMT) has proven effective in increasing functional use of the affected arm in patients with chronic stroke. The mechanism of CIMT is not well understood. Objective. To demonstrate, in a proof-of-concept study, the feasibility of using kinematic measures in conjunction with clinical outcome measures to better understand the mechanism of recovery in chronic stroke patients with mild to moderate motor impairments who undergo CIMT. Methods. A total of 10 patients with chronic stroke were enrolled in a modified CIMT protocol over 2 weeks. Treatment response was assessed with the Action Research Arm Test (ARAT), the Upper-Extremity Fugl-Meyer score (FM-UE), and kinematic analysis of visually guided arm and wrist movements. All assessments were performed twice before the therapeutic intervention and once afterward. Results. There was a clinically meaningful improvement in ARAT from the second pre-CIMT session to the post-CIMT session compared with the change between the 2 pre-CIMT sessions. In contrast, FM-UE and kinematic measures showed no meaningful improvements. Conclusions. Functional improvement in the affected arm after CIMT in patients with chronic stroke appears to be mediated through compensatory strategies rather than a decrease in impairment or return to more normal motor control. We suggest that future large-scale studies of new interventions for neurorehabilitation track performance using kinematic analyses as well as clinical scales.

Unlearning versus savings in visuomotor adaptation: comparing effects of washout, passage of time, and removal of errors on motor memory

Humans are able to rapidly adapt their movements when a visuomotor or other systematic perturbation is imposed. However, the adaptation is forgotten or unlearned equally rapidly once the perturbation is removed. The ultimate cause of this unlearning remains poorly understood. Unlearning is often considered to be a passive process due to inability to retain an internal model. However, we have recently suggested that it may instead be a process of reversion to habit, without necessarily any forgetting per se. We compared the timecourse and nature of unlearning across a variety of protocols where unlearning is known to occur: error-clamp trials, removal of visual feedback, removal of the perturbation, or simply a period of inactivity. We found that, in agreement with mathematical models, there was no significant difference in the rate of decay between subject who experienced zero-error clamp trials, and subjects who made movements with no visual feedback. Time alone did lead to partial unlearning (over the duration we tested), but the amount of unlearning was inconsistent across subjects. Upon re-exposure to the same perturbation, subjects who unlearned through time or by reverting to veridical feedback exhibited savings. By contrast, no savings was observed in subjects who unlearned by having visual feedback removed or by being placed in a series of error-clamp trials. Thus although these various forms of unlearning can all revert subjects back to baseline behavior, they have markedly different effects on whether long-term memory for the adaptation is spared or is also unlearned. On the basis of these and previous findings, we suggest that unlearning is not due to passive forgetting of an internal model, but is instead an active process whereby adapted behavior gradually reverts to baseline habits.

Plastic changes in the human H-reflex pathway at rest following skillful cycling training

OBJECTIVE The spinal cord is capable of activity-dependent plasticity, but the extent of its participation in human motor learning is not known. Here, we tested the hypothesis that acquisition of a locomotor-related skill modulates the pathway of the H-reflex, a measure of spinal cord excitability that is susceptible to plastic changes. METHODS Subjects were tested on their ability to establish a constant cycling speed on a recumbent bike despite frequent changes in pedal resistance. The coefficient of variation of speed (CV(speed)) measured their ability to acquire this skill (decreasing CV(speed) with training reflects performance improvements). Soleus H-reflexes were taken at rest before and after cycling. RESULTS Ability to establish a target speed increased and H-reflex size decreased more after cycling training involving frequent changes in pedal resistance that required calibrated locomotor compensatory action than with training involving constant pedal resistances and lesser compensation. The degree of performance improvement correlated with the reduction in the amplitude of the H-reflex. CONCLUSIONS Skillful establishment of a constant cycling speed despite changing pedal resistances is associated with persistent modulation of activity in spinal pathways. SIGNIFICANCE Recalibration of activity in the H-reflex pathway may be part of the control strategy required for locomotor-related skill acquisition.

Modulation of H-reflex excitability by tetanic stimulation

OBJECTIVE This study investigated a strategy to elicit reversible facilitation of the soleus monosynaptic H-reflex in humans using a modified tetanic stimulation technique. METHODS Interventional tetanic stimulation (ITS) was applied to the tibial nerve in the popliteal fossa, and soleus H-reflexes were recorded before and after stimulation in 15 healthy volunteers. RESULTS ITS resulted in significantly increased soleus H-reflex amplitudes that outlasted the stimulation period by approximately 16 min. The effect of ITS on soleus motor evoked potentials to transcranial magnetic stimulation and on somatosensory evoked potentials to tibial nerve stimulation was also investigated; no significant changes were found. CONCLUSIONS ITS produced a reversible increase in H-reflexes in the absence of changes in motor evoked potential or somatosensory evoked potential that outlasted the intervention period for up to 16 min. SIGNIFICANCE This technique may be used in future studies to investigate whether the induced increased H-reflex excitability influences locomotion.

Robotic therapy for chronic stroke: general recovery of impairment or improved task-specific skill?

There is a great need to develop new approaches for rehabilitation of the upper limb after stroke. Robotic therapy is a promising form of neurorehabilitation that can be delivered in higher doses than conventional therapy. Here we sought to determine whether the reported effects of robotic therapy, which have been based on clinical measures of impairment and function, are accompanied by improved motor control. Patients with chronic hemiparesis were trained for 3 wk, 3 days a week, with titrated assistive robotic therapy in two and three dimensions. Motor control improvements (i.e., skill) in both arms were assessed with a separate untrained visually guided reaching task. We devised a novel PCA-based analysis of arm trajectories that is sensitive to changes in the quality of entire movement trajectories without needing to prespecify particular kinematic features. Robotic therapy led to skill improvements in the contralesional arm. These changes were not accompanied by changes in clinical measures of impairment or function. There are two possible interpretations of these results. One is that robotic therapy only leads to small task-specific improvements in motor control via normal skill-learning mechanisms. The other is that kinematic assays are more sensitive than clinical measures to a small general improvement in motor control.

A Short and Distinct Time Window for Recovery of Arm Motor Control Early After Stroke Revealed With a Global Measure of Trajectory Kinematics

Background. Studies demonstrate that most arm motor recovery occurs within three months after stroke, when measured with standard clinical scales. Improvements on these measures, however, reflect a combination of recovery in motor control, increases in strength, and acquisition of compensatory strategies. Objective. To isolate and characterize the time course of recovery of arm motor control over the first year poststroke. Methods. Longitudinal study of 18 participants with acute ischemic stroke. Motor control was evaluated using a global kinematic measure derived from a 2-dimensional reaching task designed to minimize the need for antigravity strength and prevent compensation. Arm impairment was evaluated with the Fugl-Meyer Assessment of the upper extremity (FMA-UE), activity limitation with the Action Research Arm Test (ARAT), and strength with biceps dynamometry. Assessments were conducted at: 1.5, 5, 14, 27, and 54 weeks poststroke. Results. Motor control in the paretic arm improved up to week 5, with no further improvement beyond this time point. In contrast, improvements in the FMA-UE, ARAT, and biceps dynamometry continued beyond 5 weeks, with a similar magnitude of improvement between weeks 5 and 54 as the one observed between weeks 1.5 and 5. Conclusions. Recovery after stroke plateaued much earlier for arm motor control, isolated with a global kinematic measure, compared to motor function assessed with clinical scales. This dissociation between the time courses of kinematic and clinical measures of recovery may be due to the contribution of strength improvement to the latter. Novel interventions, focused on the first month poststroke, will be required to exploit the narrower window of spontaneous recovery for motor control.

Separable systems for recovery of finger strength and control after stroke

Impaired hand function after stroke is a major cause of long-term disability. We developed a novel paradigm that quantifies two critical aspects of hand function, strength, and independent control of fingers (individuation), and also removes any obligatory dependence between them. Hand recovery was tracked in 54 patients with hemiparesis over the first year after stroke. Most recovery of strength and individuation occurred within the first 3 mo. A novel time-invariant recovery function was identified: recovery of strength and individuation were tightly correlated up to a strength level of ~60% of estimated premorbid strength; beyond this threshold, strength improvement was not accompanied by further improvement in individuation. Any additional improvement in individuation was attributable instead to a second process that superimposed on the recovery function. We conclude that two separate systems are responsible for poststroke hand recovery: one contributes almost all of strength and some individuation; the other contributes additional individuation.NEW & NOTEWORTHY We tracked recovery of the hand over a 1-yr period after stroke in a large cohort of patients, using a novel paradigm that enabled independent measurement of finger strength and control. Most recovery of strength and control occurs in the first 3 mo after stroke. We found that two separable systems are responsible for motor recovery of hand: one contributes strength and some dexterity, whereas a second contributes additional dexterity.

Strategies for Early Stroke Recovery: What Lies Ahead?

Opinion statementMost patients experience some degree of recovery after a stroke, but the majority of patients still have persistent impairments months later. Most recovery occurs early after a stroke, in the first few weeks to months, corresponding to a period of enhanced neuroplasticity. We are beginning to understand the mechanisms that underlie this recovery process, and how we can take advantage of this plasticity in designing rehabilitative interventions. In this review, we focus on recent behavioral, pharmacological, and brain stimulation strategies that have shown promise in augmenting stroke recovery. Several studies, both in animals and humans, suggest that early initiation and high doses of therapy are crucial for maximizing the benefits of rehabilitation. The investigation of early and intensive therapy in clinical trials has been limited, likely due to the logistical challenges of conducting such studies. Other strategies for promoting recovery seek to modulate neuroplasticity or to enhance the effects of rehabilitation, including the use of pharmacological agents, stem cell therapy and non-invasive brain stimulation. While there has been recent growth in stroke recovery and rehabilitation research, there is still a great need for more basic science and clinical research to further our understanding of the stroke recovery process and develop optimal rehabilitative strategies for promoting stroke recovery.

Recovery of hand function after stroke: separable systems for finger strength and control

Loss of hand function after stroke is a major cause of long-term disability. Hand function can be partitioned into strength and independent control of fingers (individuation). Here we developed a novel paradigm, which independently quantifies these two aspects of hand function, to track hand recovery in 54 patients with hemiparesis over the first year after their stroke. Most recovery of both strength and individuation occurred in the first three months after stroke. Improvement in strength and individuation were tightly correlated up to a strength level of approximately 60% of the unaffected side. Beyond this threshold, further gains in strength were not accompanied by improvements in individuation. Any observed improvements in individuation beyond the 60% threshold were attributable instead to a second independent stable factor. Lesion analysis revealed that damage to the hand area in motor cortex and the corticospinal tract (CST) correlated more with individuation than with strength. CST involvement correlated with individuation even after factoring out the strength-individuation correlation. The most parsimonious explanation for these behavioral and lesion-based findings is that most strength recovery, along with some individuation, can be attributed to descending systems other than the CST, whereas further recovery of individuation is CST dependent.