This study investigated the feasibility, safety and efficacy of upper-extremity power training in persons post-stroke. Our main finding is that inclusion of power training (i.e., dynamic, high-intensity resistance training) in a program of upper-extremity rehabilitation is feasible, without negative consequences including either musculoskeletal compromise or exacerbation of spasticity. Functional recovery, as documented by the WMFT-FAS and other clinical indicators, was greater following HYBRID than FTP. Intervention-related effects were both retained and, in some cases, advanced during a 6-month retention period. To our knowledge, this is the first study demonstrating advancement of intervention-related improvements over a 6-month period of no additional intervention.
Several novel aspects of the intervention reported here likely contribute to our positive results: 1) high-intensity workloads with progression to advance the challenge over the course of the intervention; 2) dynamic contractions that challenged the impaired nervous system to increase movement speed and muscle power; 3) presentation of eccentric contractions which – a) increases the absolute magnitude of the training stimulus, b) involves alternative neural strategies for execution, c) requires force production throughout the full range of motion and therefore facilitate reacquisition of this critical neural mechanism of force production.
Relationship of findings to current research results
Other studies have compared strengthening and task practice for persons post-stroke in the sub-acute and chronic periods of recovery with conclusions of both favoring functional task practice. Careful examination of the methods and training parameters, however, reveals that the training approach used in the present study differed considerably. Among those previous studies, the first based strengthening on functional activities performed with either increased resistance or repetitions, while the second utilized an independent home-based program of limited scope and intensity. Most notably, therapeutic activities in both studies were not graded relative to maximal capacity and algorithms for progressive challenge of resistance training were not evident. A third study utilized a uniplanar robot to deliver a high volume of resisted upper-extremity movements, all performed in the transverse plane at table top height. Similar to the outcomes of the activity-based functional therapies described above, resisted and non-resisted robotic therapy appeared equally effective. However, the peak resistance level presented in the entire six-week robotic protocol was 28 N (~6.3# or 2.9 kg) and an algorithm for systematic progression of the resistive load was not evident. Using grip force as a proxy for upper-extremity strength, normative values for MVIC grip force average 236 N and 383 N for women and men, respectively, aged 60-69 indicating that the resistance used in this robotic study involved only 7-10% of maximal capacity. These three studies each concluded no benefit of strengthening for improving function in the hemiparetic upper-extremity. Yet, in all three cases the resistance intervention may have lacked sufficient contrast to the alternative task-specific practice approach. More importantly, in all three cases the intensity of the resistance was most likely insufficient to represent an overload stimulus, which therefore readily explains the failure to produce meaningful effects on either strength or function. Because the current study involved dynamic contractions, direct comparison to the resistance levels used in the three earlier studies is not possible. As explained in the description of the therapeutic interventions (Figure3), the training prescription in the current study differed from previously conducted studies in three ways: 1) resistance exercise targeted contractions at specific velocities, 2) intensity of the resistance required a high level of the participant’s maximal capacity and 3) work load was systematically progressed over the course of the intervention.
In contrast, a recent study utilized a robotic-type device that offered both static resistance (i.e., isometric) and repetitive arm movements at preset constant velocities (i.e., isovelocity) that required production of a minimum threshold force throughout the full range of motion. Eight weeks of training (24 sessions) using this combination of parameters (i.e., threshold force throughout the movement, dynamic contractions, systematic repetition) in persons six or more months post-stroke produced increases in grip and isometric shoulder strength ranging from 22–62% and modest gains on the UE Fugl-Meyer assessment, both outcomes comparable to those revealed in the present study. Perhaps more remarkable were significant improvements in critical parameters of reaching including: movement speed, time-to-peak velocity, minimum jerk and inter-joint coordination suggesting that repetitive training on the basis of key biomechanical parameters facilitates improved coordination of multi-segmental upper-extremity movements.
Does improved strength relate to improved function?
Weakness has long been recognized as a prominent characteristic of post-stroke hemiparesis, yet the relationship between increased strength and improved function has been elusive. Despite evidence of beneficial effects of strengthening, evidence to support concurrent effects on functional motor performance remains equivocal[55, 56]. Accordingly, prevailing clinical perspectives assert that remediation of weakness is a problem distinct from restoration of function and task-specific practice is requisite to promote improved functional performance[49, 56]. Moreover, there is strong evidence to suggest that repetitive task practice drives neural plasticity at the supraspinal level[57, 58]. Given these assertions the results of the present study are novel. HYBRID produced significant improvements not only in isometric strength, neuromotor activation and power production, but clinical parameters of impairment and functional activities. To our knowledge, only two other studies[21, 23], have reported improvement in upper-extremity function following resistance training. While we recognize that the HYBRID intervention combined functional task practice and power training, the results reveal larger effects on all measures compared to functional task practice alone. Thus, it appears that functional outcomes are improved by directly addressing the weakness component of post-stroke hemiparesis.
The majority of studies pertaining to persons post-stroke characterize weakness using isometric force measurements and from these data it has been concluded that improved strength does not contribute to improved function. Because functional task performance is dynamic, characterization of muscle performance under dynamic conditions is more relevant to understanding functional motor impairment. Indeed, intervention-related increases in dynamic torque generation have been revealed in conjunction with absence of improvements in isometric force. Power represents the capacity to generate force over time (i.e., in a moving joint). Quantification of a dynamic muscle performance parameter, such as power, may thus reveal the elusive link between strength and enhanced functional performance relevant to profoundly motor compromised populations such as post-stroke hemiparesis.
A stronger relationship has been demonstrated between power and function than between strength and function in older adults[59, 60]. The contribution of neuromotor control mechanisms to this relationship is unmistakable. For example, reduced power production in mobility-limited elders is strongly associated with the rate of EMG production. Conversely, older adults who maintain competitive fitness for power lifting retain maximal motor unit firing rates at levels comparable to healthy young individuals. High-velocity and/or explosive training increases neuromuscular and mechanical power to a greater extent than strength training and is associated with improved performance on functional tasks[59, 63]. Leveraging these findings we questioned whether the obvious manifestations of neuromotor impairment following stroke would respond similarly to older adults without neuropathology. Additional work in our laboratory, separate from this current study, has demonstrated that upper-extremity power training in isolation (i.e., not combined with FTP) is equally, if not more, effective than FTP for promoting recovery of functional upper-extremity movements.
Strength and activation changes
The early phase (i.e., 2-6 weeks) of resistance training is known to produce neural adaptations which influence the magnitude and organization of motor output (e.g., “central motor drive”) and may include: improvements in cortical excitability, alterations in motor unit recruitment threshold, changes in motor unit firing patterns (e.g., increased recruitment, rate coding, presence of doublets, motor unit synchronization, etc.)[64–67] and alteration in the patterns of force production including an increased rate of force production. Both the magnitude and time course of increased isometric strength, EMG at MVIC, and joint power in response to HYBRID are consistent with such neural adaptations.
Recent work documents both increased corticospinal excitability and marked reduction of GABA-mediated short intracortical inhibition (SICI) following 4 weeks of dynamic, high-load resistance training. While this work provides clear evidence of functional changes in the strength of corticospinal projections following resistance training, reduced SICI may be more relevant to the current study and individuals post-stroke. Corticomotor drive results from the net balance of excitatory and inhibitory influences integrated by the intra-cortical circuits. Reduced SICI reveals reduced inhibition, resulting from unmasking of silent synapses (e.g., disinhibition) and, potentially, synaptic plasticity at the cortical level[58, 71]. Excessive inhibition of the ipsilesional hemisphere is recognized following stroke and restoration of the balance of cortical excitability between hemispheres is now acknowledged as a target for motor rehabilitation. This recent demonstration of cortical disinhibition in response to dynamic, high-load resistance training suggests potential mechanisms mediating the positive neuromechanical and functional outcomes demonstrated in the present study, which can be systematically investigated in future research.
High-exertion activity does not exacerbate spasticity
Our results also reveal concurrent improvements in biceps brachii stretch reflex modulation and upper-extremity functional use in response to HYBRID. While clinical assessment using the Ashworth Scale revealed no significant changes following either FTP or HYBRID, both stretch reflex modulation (e.g., hyperreflexia) and passive torque responses (e.g., hypertonia) were significantly improved following HYBRID. Comparable effects were not revealed following FTP.
We hypothesized that high-intensity activity would not exacerbate spasticity. Unexpectedly, our findings demonstrate that high-intensity motor activity actually induces positive adaptations in reflex modulation that are retained in the absence of additional intervention. Previous work investigating the mechanisms of hyperreflexia has provided evidence for: increased/abnormal motoneuron excitability; increases in activation of dendritic persistent inward currents[74–76]; decreased presynaptic inhibition; diffuse changes at the level of spinal circuitry affecting responses in multiple muscles[78–80], and aberrant depolarizing synaptic drive. Reductions in aberrant activity, including systematic changes in the onset threshold of reflex activity as observed following HYBRID, can thus be considered positive adaptations in the direction of normal stretch reflex activity. The behavioral manifestations of neural recovery undoubtedly involve the integration of adaptations throughout the neuraxis. When studied concurrently with clinical and functional performance, reflex responses provide a means to monitor these multi-factorial physiological adaptations.
In the present study the experimental, HYBRID, intervention was compared directly to an active control intervention (FTP). The functional task practice program was developed according to principles guiding current clinical practice and afforded dose-equivalent matching for treatment time, time on task, and practitioner exposure. Repetitive task practice is argued as the intervention approach of choice for driving functional reorganization of the nervous system post-stroke[24, 49, 56]. While intervention-related effects were indeed observed in response to the control intervention, the experimental intervention produced both larger changes and a larger proportion of participants producing clinically significant improvements. In contrast to many investigations of rehabilitation efficacy[24, 83, 84], our approach was to determine whether the experimental intervention would produce greater effects than a standardized treatment developed to meet the putative parameters of current clinical practice. In so doing, we anticipated that the control intervention would reveal treatment-related gains.
Our use of a crossover design enabled us to monitor responses to both interventions in the same individuals strengthening our findings regarding differential treatment effects between HYBRID and FTP. Crossover designs offer two clear advantages. First, the influence of confounding covariates and heterogeneity between individuals is reduced because each participant serves as his/her own control. It can be expected that an intervention will produce large and small responses among individuals and similarly, that individuals may be high and low responders. Thus, the crossover can detect differential responses to therapies, should they exist. Second, optimal crossover designs are statistically efficient, thus require fewer subjects.
Crossover studies also present challenges, two of which are the potential of order effects and the potential of carry-over between treatments. It is possible that the order in which treatments are administered will affect the outcome. In the case of rehabilitation, this outcome may be genuine in that one treatment order is more efficacious or may result from a variety of influences. Clinical assessments typically used in rehabilitation are not optimally sensitive or responsive to change and thus are prone to ceiling and floor effects. Compounding these problems of clinical assessment there may be a learning effect or physiological conditioning effect in response to active therapy following a period of relatively sedentary lifestyle. Taken together, these circumstantial influences may contribute to greater responses to the first treatment, regardless of which treatment occurs first. A second concern when using a crossover design is the potential of carry-over between treatments. Carry-over effects are of particular concern in the case of rehabilitation, or exercise, where the intent is to induce persistent changes. In practice, carry-over effects can be avoided with a sufficiently long washout period between treatments. In the worst case, if treatment effects are non-specific and retained through a washout period, a crossover design would yield the obvious result – more therapy is better. In the best case, a crossover design can reveal differential effects of intervention and may suggest order effects that would optimize the ordering of activities in rehabilitation. In the present study, the differential effects of FTP and HYBRID can be appreciated across all levels of measurement, clinical, neuromechanical and neurophysiological. While period effects are suggested in some measures (e.g., Figures5 &6), they were not consistently revealed and thus contrast with our recent work. The interventions in the present study shared common elements (i.e., HYBRID involved an abbreviated program of FTP), thus the distinction of ordering may be less clear than when the interventions are contrasting. Regardless, distinct differences in the magnitude of improvements were revealed favoring the HYBRID intervention, which incorporated power training.
Given the underlying rationale of objectively assessing movement function with a standardized battery of timed tasks, one might question the choice of the observational, FAS component of the WMFT. The psychometric properties of the WMFT including validity, reliability and discriminant capacity have been established. Consideration of the FAS may be an underappreciated aspect of this literature. Since early efforts, both validity and reliability of the FAS component have been tested and reported. Furthermore, early stages of the ExCITE trial reported psychometrics of all aspects of the WMFT, including the FAS, across study sites. The FAS is equally reliable as the timed portion, and shows a significant negative correlation with performance time. The fundamental point of both these analyses and inclusion of the FAS as a component of the WMFT is that movement speed and quality of movement are interrelated. Work recently published from our lab used the WMFT to assess recovery of upper-extremity motor function post-stroke. Similar to the current study, we sought to understand the differential effects of two treatment interventions. Of note, the WMFT(time) improved equally in response to both interventions, indicating global improvements in motor function. However, kinematics (3D motion capture) differentiated treatment effects between groups with substantial effect sizes, while effect sizes for WMFT(time) were small to negligible for differences between groups. Given that the primary question in the current study was to differentiate treatment effects, we elected to report changes in the FAS score. While observational, the FAS score incorporates features of movement captured quantitatively with kinematics. Perhaps more importantly, it affords a measurement instrument readily available to the practicing clinician.
While results of the present study are encouraging, there are a number of limitations and future investigation is clearly warranted to elaborate these early findings. The small sample size limits both generalizability and the ability to better understand whether differential treatment effects occurred in higher and lower functioning participants. Further, although hand function is clearly a critical element driving use of the upper-extremity, this phase of our investigation targeted the shoulder and elbow for both strengthening and functional effects. Our intention was to determine the feasibility, safety and efficacy of performing such high-intensity activity in persons post-stroke. With these fundamental issues addressed we are able to refine the intervention for future investigation. All treatments were delivered by one physical therapist. Due to the interpersonal nature of rehabilitation practice, it is likely that an element of our results can be attributed to the positive experience participants enjoyed in receiving a substantial bout of one-on-one treatment from a therapist with whom they enjoyed a good rapport. In future work additional personnel will be involved in an effort to generalize our findings.