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Translating the science into practice: Shaping rehabilitation practice to enhance recovery after brain damage

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The revolution in neuroscience provided strong evidence for learning-dependent neuroplasticity and presaged the role of motor learning as essential for restorative therapies after stroke and other disabling neurological conditions. The scientific basis of motor learning has continued to evolve from a dominance of cognitive or information processing perspectives to a blend with neural science and contemporary social-cognitive-psychological science, which includes the neural and psychological underpinnings of motivation. This transformation and integration across traditionally separate domains is timely now that clinician scientists are developing novel, evidence-based therapies to maximize motor recovery in the place of suboptimal solutions. We will review recent evidence pertaining to therapeutic approaches that spring from an integrated framework of learning-dependent neuroplasticity along with the growing awareness of protocols that directly address the patient's fundamental psychological needs. Of importance, there is mounting evidence that when the individual's needs are considered in the context of instructions or expectations, the learning/rehabilitation process is accelerated.
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CHAPTER
Translating the science
into practice: shaping
rehabilitation practice
to enhance recovery after
brain damage
16
Carolee J. Winstein*
,†,{,1
, Dorsa Beroukhim Kay*
,{,2
*Division of Biokinesiology and Physical Therapy, Ostrow School of Dentistry,
Los Angeles, CA, USA
Department of Neurology, Keck School of Medicine, Los Angeles, CA, USA
{
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA
1
Corresponding author: Tel.: +1 323 442-2903; Fax: +1 323 442-1515,
e-mail address: winstein@usc.edu
2
Corresponding author: Tel.: +1 323 442-1196, e-mail address: dberoukh@usc.edu
Abstract
The revolution in neuroscience provided strong evidence for learning-dependent neuroplasti-
city and presaged the role of motor learning as essential for restorative therapies after
stroke and other disabling neurological conditions. The scientific basis of motor learning
has continued to evolve from a dominance of cognitive or information processing perspectives
to a blend with neural science and contemporary social-cognitive-psychological science,
which includes the neural and psychological underpinnings of motivation. This transformation
and integration across traditionally separate domains is timely now that clinician scientists are
developing novel, evidence-based therapies to maximize motor recovery in the place of sub-
optimal solutions. We will review recent evidence pertaining to therapeutic approaches that
spring from an integrated framework of learning-dependent neuroplasticity along with the
growing awareness of protocols that directly address the patient’s fundamental psychological
needs. Of importance, there is mounting evidence that when the individual’s needs are con-
sidered in the context of instructions or expectations, the learning/rehabilitation process is
accelerated.
Keywords
neurorehabilitation, restorative therapies, autonomy support, competence, self-efficacy,
motivation, neuroplasticity, patient-centered
Progress in Brain Research, Volume 218, ISSN 0079-6123, http://dx.doi.org/10.1016/bs.pbr.2015.01.004
©2015 Elsevier B.V. All rights reserved.
331
1INTRODUCTION
Over the past decade, there has been remarkable progress in understanding the
brain mechanisms that can be harnessed to enhance recovery from brain damage.
Most notable is the brain’s inherent capacity to grow new neurons, to reorganize
cortical representations, to access latent circuits, and to bypass damaged circuits by
using secondary pathways. Importantly, there is growing evidence that new inno-
vative therapeutic approaches are tapping the restorative capacity of the brain and
its neural networks. This innate brain capability is termed neuroplasticity and it
underlies all learning and memory in the healthy and damaged brain. Simultaneous
with the revolution in neuroscience, there has been considerable progress in under-
standing the social-cognitive-behavioral processes and mechanisms that enable and
empower the individual to recover voluntary control of their movements. In order
to more accurately translate the scientific advances brought about from these broad
research domains, we recognize that there must be a systematic, hypothesis-driven
and well-reasoned integration of the neuroscience and social-cognitive-behavioral
perspectives when determining how best to shape neurorehabilitation to optimize
recovery. This chapter is organized around this premise, beginning with concepts
of neuroplasticity and then integrating the most important social-cognitive-behav-
ioral concepts into a framework for translation. We set the stage for a discussion of
examples from the literature and our own work in which the integration of the sci-
ences has led to some promising therapies. These include priming the brain with
approaches that use epidural and noninvasive cortical stimulation combined with
neurorehabilitation, action observation for motor learning and stroke rehabilitation,
and tapping the intrinsic motivation circuits to maximize meaningful recovery
outcomes.
2NEUROPLASTICITY ELEVATES THE IMPORTANCE OF MOTOR
LEARNING
It took until the turn of the twenty-first century before studies began to appear in the
literature that examined motor learning in patient populations (Hanlon, 1996;
Winstein et al., 1999). At about the same time, Nudo and colleagues published in
1996 the now seminal paper in the journal Science. In that study, using a primate
model of stroke, they demonstrated the capability of the motor cortex to reorganize
the hand representation (distal forelimb) area in response to postinjury motor train-
ing, but not as a consequence of spontaneous recovery without training (Nudo et al.,
1996b). More importantly, they showed that cortical reorganization of the digit area
was the direct result of the food-retrieval practice paradigm used to train the primates
after the stroke lesion. In later work, Plautz and colleagues identified further that cor-
tical reorganization was dependent on goal-directed, task-specific, and challenging
practice, likely the result of acquisition of a new motor skill (i.e., motor learning),
332 CHAPTER 16 Translating the science into practice
and not mere repetition of grasping movements from the easiest and largest food
wells (Plautz et al., 2000).
With the advent of new brain imaging technology, it is now well accepted that the
learning of motor skills results in adaptive changes in the functional organization of
the motor system (Askim et al., 2009; Karni et al., 1995). Attempts at skilled move-
ments together with injury-induced plasticity (e.g., stroke or head injury) can influ-
ence the use of injury-affected musculature and subsequent reorganization of spared
neuronal networks (Nudo, 2003). Research over the last decade has provided consid-
erable evidence that has advanced knowledge about how to shape plasticity to en-
hance recovery after injury (Dancause and Nudo, 2011; Tennant et al., 2012).
Kleim and Jones (2008) reviewed a growing body of neuroscience research that
used a variety of models of learning, neurologic disease, and trauma from the per-
spective of basic neuroscientists, but in a manner intended to be useful for the devel-
opment of more effective clinical rehabilitation interventions. Because neural
plasticity is believed to be the basis for both motor learning in the intact brain
and relearning in the damaged brain that occurs through neurorehabilitation, the re-
cent advances in understanding experience-dependent neural plasticity can inform
the application of therapeutic interventions to promote recovery and rehabilitation.
Kleim and Jones argue that the “qualities and constraints of experience-dependent
neural plasticity are likely to be of major relevance to rehabilitation efforts in humans
with brain damage.” Recently, an interactive e-book, Neural Plasticity: Foundation
for Neurorehabilitation (Kleim, 2012), provides an updated and more fully devel-
oped expose
´of neural plasticity (especially good for students interested in the trans-
lation of neural plasticity to effective therapy programs). This e-book goes beyond a
simple literature review and begins to integrate and apply the important principles of
neural plasticity so as to inform therapeutic paradigms. For our purposes, we inte-
grate a number of the behavioral drivers from Kleim’s e-book and add some of
our own from the social-cognitive-behavioral domain integral to our integrated
framework. In so doing, we set the stage for the translational studies discussed in
the final section of the chapter.
3FROM NEUROPLASTICITY TO AN INTEGRATED
FRAMEWORK FOR TRANSLATION: WHAT ARE THE ACTIVE
INGREDIENTS?
It is now fairly well accepted that behavioral demands and motor skill acquisition are
critical drivers to cortical reorganization associated with positive functional out-
comes following a stroke or stroke-like lesion in animals (Adkins et al., 2006;
Maldonado et al., 2008; Nelles et al., 2001; Plautz et al., 2000). In nondisabled adults,
the kinematics of arm and hand movements have been shown to be uniquely con-
strained by the behavioral goals of the movement and the characteristics of the
to-be-grasped object, such as spatial location and object shape and size
3333 From neuroplasticity to an integrated framework
(Marteniuk et al., 1990; Weir et al., 1991; Wu et al., 1998). After stroke, there is ev-
idence to suggest that the emergent movement kinematics are organized differently
for real objects compared with simulated or artificial objects. Upper limb movement
kinematics were more efficient when the goal-directed activity included reaching for
a ringing telephone, compared to simulated contexts such as reaching for a stick
(Trombly and Wu, 1999) or no object (Wu et al., 1998). Thus, the fidelity of the task
in the natural context seems to be a critical ingredient of effective therapeutic pro-
grams. In addition, greater transfer of training to life activities might be anticipated
from such task-specific training, particularly given the focus on familiar everyday
tasks, and transfer to unpracticed tasks might be possible given the focus on the de-
velopment of problem-solving strategies.
It is well known that training programs that are designed to enforce the practice of
problem-solving usually are more effective for learning than those that are drill-like
and enforce mere repetition of the previous solution to the movement problem
(Bernstein, 1967; Lee et al., 1994). Taken together, and compiled from perspectives
including brain, cognitive, and the social sciences, we propose a minimum of three
active ingredients thought to be critical for effective translation of the science into
effective therapeutic practice. These active ingredients must engage and empower
the individual. To do so, they must (1) be challenging (Plautz et al., 2000), (2) be
progressive and optimally adapted over practice (Lee and Wishart, 2005a; Sanger,
2004), and (3) solicit intrinsic motivation and active participation (Lee et al.,
1991; Lewthwaite and Wulf, 2012). It should be noted that these three criteria likely
are not independent, but rather overlap and are complimentary in nature. In the next
section, we unpack each active ingredient within the context of the behavioral drivers
thought to be important for translation and through a focused discussion of the foun-
dational basic and clinical research.
4ACTIVE INGREDIENT #1: BE CHALLENGING
4.1 PRACTICE SHOULD BE DIFFICULT BUT NOT TOO DIFFICULT
Practice should be challenging/difficult enough to require new learning, and engage-
ment with attention to solve the motor problem (Plautz et al., 2000). Challenge and
difficulty are essentially two sides of the same coin. Basically, the perceptual expe-
rience of a challenging situation may be one of difficulty. If learning something new
does not come easily, by definition, it is difficult, but not impossible. There is sub-
stantial evidence from the behavioral, computational, neuroscience, and social psy-
chological literatures for the beneficial effects on motor skill learning of practice
conditions in which the difficulty of the task matters (Abe et al., 2011; Carey
et al., 2005; Chiviacowsky et al., 2012a; Cross et al., 2007; Goh et al., 2012; Lee
and Wishart, 2005a; Lee et al., 1994; Schweighofer et al., 2011). The level of task
difficulty can be manipulated through practice schedules, contextual factors,
dual tasking, and the actual task requirements (e.g., precision, magnitude, degrees
334 CHAPTER 16 Translating the science into practice
of freedom). On the other hand, perceived task difficulty can be manipulated through
simple statements before practice that have been shown to increase confidence
(i.e., self-efficacy) and impact motor learning (Lewthwaite and Wulf, 2012). This
topic is expanded further in the last section with examples of tapping the motivation
circuits to enhance recovery.
4.2 PRACTICE MUST BE SPECIFIC
The challenging nature of the training experience dictates the nature of the plasticity.
“Practice must be specific” implies that specificity of training is important. Indeed,
specificity effects are one of the oldest and most common findings in learning and
memory research (Thorndike, 1913). Later in the twentieth century, work in the
transfer of skills again supported a specificity effect, with the general finding that
transfer of training was small unless the skills were essentially identical to one
another (Schmidt and Young, 1987). Similarly, a specificity effect was found in ex-
periments in which participants learned a task during practice and then performed it
under similar or changed conditions in a transfer test (Tremblay and Proteau, 1998).
As predicted by the specificity effect, performance was usually most effective when
the transfer conditions matched those conditions that were available during the prac-
tice session. Therefore, there is considerable evidence suggesting that motor skills
are represented in memory in a highly specialized way (Keetch et al., 2005). Recent
work suggests that there are neural constraints on learning whether it be motor, sen-
sory or cognitive learning (Sadtler et al., 2014). Using a brain–computer interface
paradigm in which Rhesus macaques controlled a computer cursor by modulating
neural activity patterns in the primary motor cortex, Sadtler and colleagues suggest
that the existing structure of a network can shape learning. Using a timescale of
hours, this group showed that it was more difficult to learn to generate neural activity
patterns that are not consistent with the existing network structure. As such, a
network-level explanation is offered for the observation that one is more likely to
learn new skills when those skills are related to the skills that one already possesses.
Recent behavioral findings from an examination of individuals with chronic
hemiparesis supports such a network-level explanation as proposed (Sadtler et al.,
2014), but here applied to the generalization of learning. In a small-scale study
(N¼11), Schaefer et al. (2013) tested whether training on one motor task (i.e., feed-
ing task) would transfer to untrained tasks that were either spatiotemporally similar
(i.e., sorting) or different (i.e., dressing) in individuals with chronic hemiparesis
poststroke. Interestingly, after 5 days of supervised massed practice (continuous
practice with few or no rest between trials) of a feeding task, performance of all three
tasks improved significantly after training. Further, the amount of improvement in
the untrained tasks was comparable to that of the trained tasks but not dependent
on the degree of similarity to the trained task. Given the small sample, these results
are clearly not definitive, but rather suggestive that the effects of upper-extremity
task-specific training can transfer to other untrained tasks in individuals with chronic
mild-to-moderate hemiparesis. Besides a network-level explanation for this
3354 Active ingredient #1: be challenging
generalization/transfer effect, another explanation may be one mediated by a phe-
nomenon in which the mindset is altered through successful practice (e.g., improved
self-efficacy or confidence to use the limb in a specific way) and this in turn impacts
future attempts to use the paretic limb for untrained tasks. Understanding how these
social-cognitive factors modulate motor learning and transfer will be important for
future translational research to better shape practice to enhance recovery
(Lewthwaite and Wulf, 2012).
Taken together, the literature regarding specificity of training shows that al-
though general exercise and strengthening programs are thought to be effective when
combined with task-specific training paradigms, the direct benefits are usually
expressed at the system level (i.e., physiology, musculoskeletal) and not at the level
of the specific task or skill that is being trained. Recent work has begun to examine
the degree to which practice on one task actually transfers in meaningful ways to
another task. Integrating the social-cognitive-behavioral perspective into this line
of enquiry will be essential to advance translational work in this area.
4.3 PRACTICE MUST BE INTENSE
Induction of plasticity requires sufficient training intensity to be optimally challeng-
ing. Intensity implies that the dose, frequency, and duration of training are important
parameters in the design of any effective task-oriented training program. Intensity is
usually defined as an exceptionally great concentration, power, or force. In the field
of physics, it is the amount or degree of strength of electricity, light, heat, or sound
per unit area or volume. There is considerable evidence to support this idea, but ex-
plicit guidelines for what constitutes a “sufficient” level of intensity is sorely lacking.
The so-called pharmacokinetics includes “dosing of training” and has been identified
as both a challenge and an important unmet need in the design of clinical trials in
rehabilitation. The importance of “therapy dose” in neurorehabilitation is reflected
in a recent trend for clinical trials of complex interventions to include at least one
dose-equivalent control group in the design (Duncan and Velozo, 2007; Winstein
et al., 2013a). In translating from animal models (Birkenmeier et al., 2010;
Murphy and Corbett, 2009) to human clinical practice, Krakauer and colleagues sug-
gest that there will need to be a substantial increase in the intensity and dosage of
treatments offered in the first month after stroke with an emphasis on impairment
(Krakauer et al., 2012). It is our view that including several powerful social-
cognitive-behavioral manipulations such as a simple statement pertaining to a pos-
itive concept of ability and including self-management strategies may offset the need
for a higher dose of therapy. In other words, tapping the intrinsic motivational cir-
cuits for motor learning may be more effective in the long term (i.e., durability and
quality of life) and for benefits that impact the person and their quality of life, than
simply increasing the dose of training with a focus on impairment mitigation. We
describe this more in Section 7 dealing with examples of new therapies with a dis-
cussion of an integrated model designed to accelerate recovery.
336 CHAPTER 16 Translating the science into practice
5ACTIVE INGREDIENT #2: BE PROGRESSIVE AND OPTIMALLY
ADAPTED
5.1 PRACTICE IS “REPETITION WITHOUT REPETITION”
Practice should be progressive and optimally adapted such that over practice, the task
demand is optimally adapted to the patient’s capability and the environmental con-
text. It must not be too simple or repetitive to not challenge, and not too difficult to
cause a failure of skill acquisition or a low sense of competence (Lee and Wishart,
2005b; Sanger, 2004). Extending the environmental context outside the laboratory
or clinic is an important aspect of an optimally adapted patient-centered program.
This reinforces the “real-life” benefits through a virtuous cycle that becomes
self-sustaining.
Induction of plasticity requires sufficient repetition that is progressive and adap-
tive. This suggests that repeated attempts to solve the motor problem benefits plas-
ticity and learning. There is considerable evidence for this idea that comes from the
motor learning literature and is reviewed extensively, elsewhere (Winstein et al.,
2015). What is less understood is how the organization of those repetitions (e.g.,
massed vs. distributed) should be structured for the best outcomes. What is clear
from the evidence to date is that mere repetition of simple tasks that are well within
the capability of the performer will most certainly not induce neural plasticity or
learning (Plautz et al., 2000). Basically, when the system acquires a new skill
through practice, each repetition is not exactly the same as the previous attempt
at the action. Even when you try to solve the motor problem in the same way each
time, it is nearly impossible to control all the degrees of freedom with exactly the
same timing of muscle activity and joint excursions. Most well-learned goal-
directed actions reveal variability across trials in the trajectory of the movement,
but consistency in the goal or endpoint of the movement (Kempf et al., 2001). It
is likely that Bernstein’s observation that “practice is repetition without repetition”
is profound and fundamental to advancing understanding in this area of study (Lee
et al., 1991).
The past decade has witnessed an explosion of different therapeutic interventions
for stroke rehabilitation emergent from new insight about the brain–behavior rela-
tionship. The experience-dependent approach contends that repetitive practice of
specific tasks leads to functionally relevant reorganization of sensory and motor cor-
tical areas. More importantly, “maladaptive” plasticity such as the nonuse of the af-
fected limb can lead to “learned nonuse” beyond the neural constraints of the lesion
(Sunderland and Tuke, 2005; Taub et al., 2006b). Maladaptive or “bad use” can occur
when less optimal solutions—ones that rely on compensatory strategies—are used
(Corti et al., 2012; Kitago and Krakauer, 2013; Kitago et al., 2013; Levin et al.,
2009; Lum et al., 2009; Michaelsen and Levin, 2004; Michielsen et al., 2012;
Shaikh et al., 2013; Tan et al., 2012; van Kordelaar et al., 2012; Winstein et al.,
2015). These maladaptive responses, if left unchecked, can result in poor health
and suboptimal function. This in turn contributes to the incipient decline after
3375 Active ingredient #2: be progressive and optimally adapted
therapy ends and gains are not generalized. We refer back to this problem later in
Section 7.1.1 concerning epidural cortical stimulation.
The problem therefore is how to resolve the dilemma between the known benefits
of intense, challenging, and progressive task practice programs, and the poor trans-
fer, generalization, and persistence of gains made in therapy to outside of therapy
use. Recently, we suggested an evidence-based solution—one where the benefits
of progressive, task practice systems could be integrated with patient-centered strat-
egies to facilitate translation of the therapeutic gains into skilled use in the home and
community—one in which the patient is empowered to incorporate the paretic limb
into valued activities (Wade and Winstein, 2011; Winstein et al., 2013b). We elab-
orate on this further at the end of the chapter in Section 7.2, examples of promising
new therapies.
Previous attempts to harness technology (e.g., rehabilitation robotics) to address
the poststroke arm and hand recovery problem, including the multicenter VA robot
study (Lo et al., 2010) and the recent three-dimensional, task-specific robot therapy
trial (Klamroth-Marganska et al., 2014), have generally assumed a relatively narrow
perspective (e.g., automated repeated task practice) and lacked a strong conceptual
framework for the intervention. This problem is not unique to technology-based in-
terventions; in fact, it characterizes most of the task-oriented approaches (e.g.,
mCIMT (Page and Levine, 2007) including task-specific training (Platz et al.,
2001; van Delden et al., 2013)) and most impairment-focused approaches (e.g.,
(Platz et al., 2005; Thielman, 2004)). Previous attempts to combine task-oriented
and impairment-focused training have been more successful for specific severity-
level groups (e.g., Corti et al., 2012; Winstein et al., 2004). However, the failure
of the more limited approaches to demonstrate the expected superiority overdose
matched usual therapy, particularly at distal endpoints (e.g., 1 year later) sometime
after the therapy program has ended, is not particularly surprising when considering
that the rehabilitation problem is multifaceted, including limitations in capacity (e.g.,
strength), function (e.g., reaching and grasping), and motivation (e.g., self-efficacy
to use the paretic limb), and perhaps more importantly, requires the motivation and
self-management skills to alter one’s behavior in the long term.
5.2 TIMING OF PRACTICE MATTERS
Different forms of plasticity occur at different times during training. This implies that
timing of an intense, therapy program is an important factor and needs to be adapted
accordingly. Most of the clinical research up until recently has been conducted in the
chronic phase of stroke recovery. The reason for this choice is complex and multi-
faceted (e.g., confounded by spontaneous recovery and safety concerns related to
glutamatergic toxicity observed in animal studies). However, recent evidence from
animal and human studies suggests that earlier interventions would likely have a
greater impact on important outcomes (Barbay et al., 2006; Biernaskie et al.,
2004; Hsu and Jones, 2005; Murphy and Corbett, 2009). In a provocative point of
view, Krakauer and colleagues argue for focused high-intensity interventions offered
338 CHAPTER 16 Translating the science into practice
in the first month after stroke (Krakauer et al., 2012). This proposal is reflected in the
recent NINDS priority program for translational research targeting early recovery
after stroke in humans (NINDS, 2012).
6ACTIVE INGREDIENT # 3: SOLICIT MOTIVATION AND ACTIVE
PARTICIPATION
6.1 USE IT OR LOSE IT—OR STAY ACTIVE AND ENGAGED FOR
MAXIMAL BENEFIT
Failure to drive specific brain functions can lead to functional degradation. “Use it or
lose it” implies that any therapeutic intervention that encourages or promotes “use”
of the paretic limb should be considered. Task-specific training, Constraint-Induced
Movement Therapy (CIMT), bilateral arm training, and functional task practice are
just a few examples of therapeutic programs from the clinical literature that are pred-
icated on the “use it or lose it” behavioral driver. Recently, to better understand the
interactions between arm function and use in humans poststroke, Schweighofer and
colleagues used a computational approach to develop a first-order dynamical model
of stroke recovery with longitudinal data from participants receiving constraint-
induced movement therapy in the EXCITE clinical trial (Hidaka et al., 2012). Of
most import, by comparing the model parameters before and after CIMT intervention
delivered relatively early after stroke (i.e., 3–9 months after stroke) to those receiving
the intervention 1 year after randomization (i.e., control group), they found that
CIMT increased the parameter that controls the effect of arm function on arm
use. Increase in this parameter, which can be thought of as the confidence to use
the arm for a given level of function, leads to an increase in spontaneous use after
therapy compared to before therapy. So it appears from this dynamical model result
that self-efficacy for arm use may be an important mediator of continued use after
therapy ends. While extrinsic motivators like constraints on the stronger limb and
rehabilitation robotic devices on the paretic limb can have direct effects on paretic
arm use at the time, they may indirectly foster aspects of intrinsic motivation such as
self-efficacy for arm use that enable long-term benefits after therapy ends. In the next
section, we discuss how extrinsic and intrinsic forms of motivation have been tapped
to enhance motor learning and restore function after brain damage.
6.2 MOTIVATION ENHANCES MOTOR LEARNING
Numerous therapeutic approaches including CIMT, bilateral arm training, and some
forms of rehabilitation robotics have relied upon extrinsic forms of motivation to so-
licit engagement and enhance recovery through intense practice paradigms. For ex-
ample, in CIMT protocols, restraint of the less-affected limb solicits extrinsic
motivation to promote use of the affected limb. Figure 1 taken from Sunderland
and Tuke (2005) uses the term “motivation” (i.e., extrinsic motivation) within the
339Active ingredient # 3: solicit motivation and active participation
classic learned nonuse model originally proposed by Taub et al. (1994). In bilateral
arm training, mechanical or robotic devices can be thought of as a form of extrinsic
motivation to engage movement of the affected limb. Moreover, the seminal work of
Nudo et al. (1996a) used two forms of extrinsic drive (i.e., hunger and restraint of the
nonparetic limb) to motivate food retrievals with the paretic limb from progressively
smaller wells of the Kluver Board.
The reward literature supports the positive impact of monetary reward or other
external motivators to enhance learning and motor behavior (Abe et al., 2011;
Kojovic et al., 2014). Recent neuroimaging studies have revealed mechanistic pro-
cesses that may support the impact of motivation in enhancing learning and recovery
(Mendelsohn et al., 2014; Nishimura et al., 2011). Furthermore, there is now neuro-
anatomical evidence from a rat model that the primary motor cortex (MI) receives a
dopaminergic projection from the ventral tegmental area (VTA), a region known to
signal reward, and that this projection in turn mediates the learning of motor skills by
inducing cellular plasticity events in MI (Hosp et al., 2011). These findings provide
neurophysiological evidence for MI plasticity and the determination that these do-
paminergic terminals in MI that originate in VTA are necessary for successful motor
skill learning.
From the social-cognitive-behavioral literature, there is mounting evidence that
attention to an individual’s fundamental psychological needs can engage elements of
intrinsic motivation which in turn can impact motor skill learning and neurorehabil-
itation outcomes including long-term behavioral engagement and self-efficacy. Re-
cent work investigating the motivational factors that support the three fundamental
High effort
Contracted cortical
limb representation
due to nonuse
Suppression of ability
due to subacute
conditioning
Positive
reinforcement.
Learned compensation
of using nonparetic
limb
Increased
motivation
Task
practice
Learned
non-use.
Low spontaneous hand use
+ poor functional ability
FIGURE 1
In this model of learned nonuse, increased motivation refers to the use of an external
constraint device on the nonparetic limb.
Adapted from Sunderland and Tuke (2005).
340 CHAPTER 16 Translating the science into practice
psychological needs for competence, autonomy support, and social relatedness
(Bandura, 1997, 2004; Deci and Ryan, 2000; Ryan and Deci, 2000) has demonstrated
an important role in promoting motor learning, as reflected in acquisition and reten-
tion of motor skills in both clinical and nonclinical populations (Chiviacowsky et al.,
2012b; Dobkin et al., 2010; Lewthwaite and Wulf, 2012; Wulf et al., 2012). We elab-
orate on this important work in the examples of new therapies (see Section 7.1.4).
The fundamental psychological need for competence is perhaps one of the most
important needs with relevance to the rehabilitation setting. The need for perceived
competence may be an important mediator for therapeutic approaches based on the
“use it or lose it” perspective. As mentioned earlier, the modeling work that used
EXCITE data (Hidaka et al., 2012) and more recently the laboratory-based explora-
tion of the relationship of self-efficacy and probability of choosing the paretic limb
for a target-reaching task (Chen, 2011) point to the importance of building confi-
dence to use the affected arm and hand within efforts to optimize motor learning
or relearning. Chen found a very strong positive correlation (r¼0.907) between
task-specific self-efficacy and the probability of choosing the paretic limb in a
free-choice aiming task condition in a group of 15 participants who were in the
chronic phase poststroke. Interestingly and consistent with others, there was no cor-
relation between motor capability (i.e., Fugl–Meyer score) and spontaneous arm
choice in the free condition (r¼0.352). What is important to underscore from these
findings is that it is not enough to develop better control, coordination, and success at
arm and hand tasks unless the confidence to use the limb ubiquitously is also devel-
oped. One often implicit and faulty assumption is that the development of confidence
will automatically follow the development of capability. In fact, the capability–
confidence linkage is often compromised after the disabling consequences of stroke
or head injury. The evidence for this is strong and from varied sources including the
following: (1) learned nonuse (Sunderland and Tuke, 2005; Taub et al., 2006a) and
the well-known adage, “He can, but does he?” (Andrews and Stewart, 1979); (2) the
only weak to moderate relationship between motor capability (i.e., UE Fugl–Meyer)
and spontaneous arm use (i.e., MAL amount of use) quantified by Sterr et al. (2002)
using a free and forced version of the Actual Amount of Use test; (3) a more recent
quantification of nonuse by our group using the Bilateral Arm Reaching Test-BART
(Han et al., 2013); and (4) the discrepancy between recovered motor ability and
patient-reported hand use observed in some patients (Stewart and Cramer, 2013).
To foster persistent use of the paretic arm, we posit that it is necessary, initially at
least for one to choose to use the paretic arm for a given functional action, despite
concerns about its present capacity to perform the action. To engage in using the pa-
retic arm persistently, it is important that participants feel some degree of confidence
that their paretic arm can accomplish the action and that the kinds of practice en-
gaged will result in positive outcomes in the future. Feeling confident about one’s
ability to attain a specific level of performance in a given environment is known
as self-efficacy. Only recently has self-efficacy been studied in the context of stroke
disability to understand its importance and relationship with physical impairment
and functional outcomes (Hellstrom et al., 2003; Jones and Riazi, 2011;
Robinson-Smith and Pizzi, 2003; Salbach et al., 2006). Researchers have
341Active ingredient # 3: solicit motivation and active participation
consistently reported that self-efficacy may play an important role in reducing fear of
falling, improving walking ability, and increasing quality of life. However, the ev-
idence in the context of stroke rehabilitation has been almost exclusively related to
lower limb actions such as balance and gait. The relationship between self-efficacy
and rehabilitation outcomes for the upper limb has not been studied until very re-
cently and primarily by our group (Chen and Winstein, 2009; Chen et al., 2013;
Winstein et al., 2013b).
6.3 PRACTICE SHOULD BE SALIENT AND MEANINGFUL FOR OPTIMAL
ENGAGEMENT
The training experience must be sufficiently salient to induce plasticity. Salience im-
plies that the training must have the quality or state of being “salient.” It must be
prominent or stand out conspicuously or be noticeable. There has been considerable
discussion about the nature of the recovery process from the patient’s perspective
(Barker and Brauer, 2005; Barker et al., 2007; Sabini et al., 2013). Barker et al.
(2007) reported that the single most important factor that contributed to upper limb
recovery, from the perspective of the stroke survivor and through self-report, was
“use of the arm in everyday tasks.” From this observation, we suggest that a thera-
peutic program that includes participant-selected meaningful tasks will likely be
viewed as most salient in the context of the recovery process. In support of this notion,
a recent qualitative study to identify themes and possible mechanisms of recovery of
the hand suggested a therapeutic framework for continued rehabilitation and research
that includes the patient’s perspective (Sabini et al., 2013). This is clearly in line with
recent Institute of Medicine initiatives that call for more patient-centered strategies of
health care (Institute of Medicine, 2001, 2012; Institute of Medicine et al., 2001).
The last section of this chapter culminates with examples from the literature and
our own work in which the integration of the sciences has led to several new and
promising restorative therapies. These include four methods thought to “prime the
brain” including epidural and noninvasive cortical stimulation combined with neu-
rorehabilitation, action observation, and ways of tapping the motivational circuits.
For our last example, we introduce an integrated model of neurorehabilitation that
we developed which includes overlapping constructs of skill, capacity, and motiva-
tion, termed the Accelerated Skill Acquisition Program (i.e., ASAP).
7EXAMPLES OF PROMISING NEW THERAPIES
7.1 METHODS FOR PRIMING THE BRAIN
7.1.1 Direct Cortical Stimulation Combined with Rehabilitation
The most recent NINDS stroke priorities (NINDS, 2012) specifically targeted
“Translational research using neural interface devices for stroke and other neurologic
disorders.” The recent failure of the industry-sponsored multisite pivotal trial
342 CHAPTER 16 Translating the science into practice
(i.e., Phase III Randomized Control Trial) of targeted subthreshold epidural cortical
stimulation delivered concurrently with intensive rehabilitation therapy warranted a
critical appraisal and reanalysis. There had been considerable preclinical animal
work (Adkins-Muir and Jones, 2003; Kleim et al., 2003; Teskey et al., 2003) and
Phase 1 and II small-scale pilot clinical trial work to test and develop the Phase
III trial protocol (Brown et al., 2003, 2006; Harvey and Winstein, 2008; Huang
et al., 2008; Levy et al., 2008). Plow et al. (2009) summarized their concerns regard-
ing cortical stimulation with the following comments: “it is important to determine
the (1) location of peri-infarct representations by integrating multiple neuroanatom-
ical and physiological techniques; (2) role of other mechanisms of stroke recovery;
(3) viability of peri-infarct tissue and descending pathways; (4) lesion geometry to
ensure no alteration/displacement of current density; and (5) applicability of lessons
generated from noninvasive brain stimulation studies in humans. In terms of com-
bining stimulation with rehabilitation, we should understand (1) the principle of ho-
meostatic plasticity; (2) the effect of ongoing cortical activity and phases of learning;
and (3) that subject-specific intervention may be necessary.” These points highlight
the problems of transitioning from animal to human models and other important fac-
tors pertaining to the translation of basic principles for interventions to promote
stroke recovery including patient-specific issues.
The primary outcome from the Everest trial was never published, likely because
of the negative results. This was an industry-sponsored trial (Northstar, Inc.) with
FDA approval. When the primary efficacy endpoint was not achieved, the Industry
sponsor folded and further development of the CS device was discontinued. In an
effort to enhance reproducibility in biomedical research, the NIH is currently explor-
ing several initiatives to restore the self-correcting nature of preclinical research and
the entire biomedical research enterprise as a whole (Collins and Tabak, 2014). One
of these initiatives is to encourage the publication of negative findings to make the
research process more transparent to the biomedical research community. In this vein
and in spite of the negative findings, the Everest trial investigative team reexamined
the trial outcomes in order to prepare the primary outcome paper for publication. This
work is to be published soon in a special issue of Neurorehabilitation and Neural Re-
pair on epidural stimulation.
Briefly, the Everest trial was a single-blind, multicenter study that assessed the
safety and effectiveness of combining motor cortex stimulation (CS) with rehabili-
tation in improving upper limb motor function in ischemic stroke patients with
moderate to moderately severe hemiparesis (Harvey and Winstein, 2008). The pri-
mary efficacy endpoint was defined as an improvement of 4.5 points in the upper-
extremity Fugl–Meyer scale and 0.21 points in the Arm Motor Ability Test 4 weeks
after a 6-week epoch of rehabilitation, for a total of 65 h of therapy. The primary
efficacy endpoint was met by 32% and 29% of investigational and control
(rehabilitation only) patients, respectively (p¼0.36), and by 69% (n¼9/13) of the
investigational patients in whom movements could be elicited by the stimulation
testing (noted in the Plow et al., 2009 review). However, at 24 weeks postrehabilita-
tion, a greater (p¼0.003) proportion of investigational (39%) than control (15%)
3437 Examples of promising new therapies
patients maintained or achieved the primary endpoint. While efficacy of com-
bined epidural cortical stimulation with rehabilitation was not evident 4 weeks
postrehabilitation (i.e., primary efficacy endpoint), compared with rehabilitation
alone, the combined intervention resulted in superior outcomes after 24 weeks,
and in the majority of patients in whom movements were elicited during motor
threshold testing.
The fact that a greater proportion of the CS + Rehab group compared to the
Rehab only group maintained or achieved the primary endpoint sometime between
12 and 24 weeks after rehabilitation ended suggests a time-dependent mechanism
was operating. In fact, 50% of the control group participants that had achieved
the endpoint at 4 weeks maintained that level at 24 weeks (29% at 4 weeks vs.
15% at 24 weeks). This decline or lack of durability in task-specific training
interventions was discussed earlier in Section 5.1 describing repetitive practice pro-
tocols. We argued there that the training may have led to maladaptive short-term
movement solutions, ones that do not persist after therapy ends in delayed or
transfer conditions (e.g., home and community). This pattern of results is also
reminiscent of the well-known performance-learning distinction in which the
benefits to motor skill performance between immediate and delayed/transfer tests
is lost (Kantak and Winstein, 2012). To summarize, the Everest trial findings
suggest that CS may have supported the consolidation of what was learned during
rehabilitation. Rehabilitation alone led to improvements, but those gains were not
maintained to the same degree as for the CS + Rehab group. This interpretation
has important implications for understand the mechanism of CS for future work
in this area. To the point, subthreshold CS may be thought to prime the brain
through use-dependent plasticity processes to consolidate gains from the therapy
program. We discuss related findings using noninvasive cortical stimulation in the
next section.
7.1.2 Noninvasive Cortical Stimulation Before or After Rehabilitation
Avenanti and colleagues demonstrated that low-frequency rTMS promotes use-
dependent motor plasticity in chronic stroke using a cleverly designed randomized
trial (Avenanti et al., 2012). Their aim was to investigate the long-term behavioral
and neurophysiologic effects of combined time-locked rTMS and physical therapy
intervention in chronic stroke patients with mild motor disabilities. Thirty patients
were enrolled in a double-blind, randomized, single-center clinical trial. Participants
received 10 daily sessions of 1 Hz rTMS over the intact motor cortex. In different
groups, rTMS stimulation was either real or sham and was administered immediately
either before or after physical therapy. Outcome measures included dexterity, force,
interhemispheric inhibition, and corticospinal excitability and were assessed for 3
months after the end of treatment to determine persistence of any effects. With regard
to mechanism, they reported a treatment-induced cumulative rebalanced excitability
in the two hemispheres and a reduction of interhemispheric inhibition in the groups
that received real rTMS. Use-dependent improvements were detected in all groups.
344 CHAPTER 16 Translating the science into practice
Improvements in trained abilities were small and transitory in the sham rTMS group
(therapy only effect). They found greater behavioral and neurophysiologic benefits
from real rTMS with the group receiving the rTMS before physical therapy showing
robust and stable improvements compared to the group receiving rTMS after phys-
ical therapy. These results suggest that priming motor networks with rTMS can
promote effective use-dependent plasticity. These findings demonstrate that
hypothesis-driven multimodal combination therapies using noninvasive brain stim-
ulation that implement known mechanisms of neuroplasticity can be developed for
future clinical use. Future work will need to determine if the present findings can be
extended to stroke patients with moderate to more severe motor impairments.
7.1.3 Action Observation for Motor Learning and Neurorehabilitation
An exciting research frontier involves the mirror neuron system (Fadiga et al., 1995).
Evidence for a human mirror neuron system and action observation network is
mounting (Avenanti et al., 2007; Heiser et al., 2003). However, there still is consid-
erable controversy and confusion about the homologue to the primate mirror neuron
system (Dinstein et al., 2008) as well as the purpose of the action observation net-
work (Cross et al., 2009) in humans. Studies have been conducted to examine the
sensitivity of the action observation network to physical and observational learning
in humans (Cross et al., 2009). A provocative review suggested that the mirror neu-
ron system might provide a useful circuitry to enhance recovery of the severely af-
fected upper limb early after stroke (Pomeroy et al., 2005). One of the first studies
that provided empirical support for the use of action observation with intent to im-
itate in the context of stroke rehabilitation was published in 2007 (Ertelt et al., 2007).
Recently, action observation was classified as one of several specific priming tech-
niques to increase the excitability of the stroke-affected motor system and promote
plastic reorganization in response to subsequent practice of physical activity
(Pomeroy et al., 2005). A small-scale study with eight chronic stroke patients pro-
vided evidence that a single session of action observation that was congruent with
the practiced movement (i.e., voluntary thumb movement in a specific direction) en-
hanced motor memory more than practice alone or action observation of thumb
movements that were incongruent to the practiced movement (Celnik et al.,
2008). However, a recent translational RCT found that observation-to-imitate plus
practice for 15 days of treatment could add little to physical therapy benefits early
after stroke (within 31 days) (Cowles et al., 2013). Given the variable response to
action observation in the stroke population, it will be important to understand
how the stroke brain responds to action observation.
Garrison and colleagues conducted the first functional magnetic resonance imag-
ing investigation to determine if and how the motor system is modulated by action
observation after stroke (Garrison et al., 2013). Functional MRI was used to compare
brain activity during right- and left-hand action observation in right-handed nondis-
abled matched participants (N¼12) and participants who were right-handed before
left hemisphere stroke (N¼12). Action observation was found to activate specific
motor plans in damaged motor circuits after stroke, and this activity was related
3457 Examples of promising new therapies
to the motor capabilities to perform the same actions. Cortical motor activity during
action observation may be relevant to motor learning and to motor relearning in
stroke rehabilitation. Harnessing the action observation network after stroke repre-
sents an exciting frontier for neurorehabilitation and a potentially important under-
utilized circuit for driving relevant recovery after stroke.
7.1.4 Tapping the Intrinsic Motivation Circuits
Patient motivation has been recognized as playing an important role in rehabilitation
outcome (Maclean and Pound, 2000). Recent evidence supports the use of various
strategies that engage the motivation system and can be incorporated into rehabili-
tation therapy to elevate the patient’s intrinsic motivation.
Consideration of an individual’s fundamental psychological needs for compe-
tence, autonomy, and social relatedness within the framework of rehabilitation ther-
apy is an effective way to employ intrinsic motivation and positively benefit motor
learning and recovery. People’s beliefs and expectations regarding their ability (i.e.,
competence) are one of the three fundamental psychological needs shown to have an
impact on motor learning in important ways (Dweck and Leggett, 1988). Research to
determine the effects of simple statements pertaining to expectation of performance
and positive concept of ability reveals significant influences on perceptions of task
difficulty and beneficial effects on the learning of motor skills (McKay et al., 2012;
Wulf and Lewthwaite, 2009; Wulf et al., 2012). For example, relative to a control
group, older women learning a novel balance task and who were provided a single
statement prior to beginning indicating that “active people like you, with your expe-
rience, usually do very well on this task” retained learning, balanced longer, and had
higher self-efficacy on a delayed test of learning (Wulf et al., 2012).
Instructions related to the nature of the skill and one’s concept of ability, given
before practice, can also influence motor behavior (Lewthwaite and Wulf, 2012). For
example, three groups of young adults were asked to balance on a horizontal plat-
form. All three groups were given instructions to balance for as long as they could
in each 90-s trial. At the start of practice, two groups received an additional statement
about the nature of the task (i.e., task is an acquirable skill or it is a fixed capacity/you
either have it or you do not). The third received no additional information. The group
that received the acquirable skill information showed better performance during ac-
quisition and retention sessions compared to that of the two other groups (Wulf and
Lewthwaite, 2009).
Finally, Dobkin and colleagues used a very simple feedback manipulation and
demonstrated that individuals in inpatient stroke rehabilitation who were given feed-
back and encouragement of daily timed gait trials walked significantly faster both at
discharge and 3 months later than those not provided with their gait times and en-
couragement (Dobkin et al., 2010). The specific feedback and encouragement in-
cluded a statement that indicated their walking performance was “very good!,”
information about the amount of time they walked the trial (number of seconds), fol-
lowed by a statement (a) informing their improvement from the previous trial,
(b) indicating the individual’s control over walking speed (“This shows you are
346 CHAPTER 16 Translating the science into practice
holding your own”), or (c) demonstrating enhanced expectation of walking perfor-
mance (“I believe that you will soon be able to walk a bit faster”). While Dobkin and
colleagues’ results are not surprising, from a social-cognitive-behavioral perspec-
tive, the biggest surprise was that the control group which was not provided with their
times and encouragement during routine gait training represented the standard of
care across these international stroke rehabilitation centers enrolling their patients
into the SIRROWS trial.
Results from these studies have profound implications for the positive impact of
engaging intrinsic motivation within the rehabilitation setting. These findings indi-
cate that simple motivational statements (i.e., encouraging expectation of recovery
and positive concepts of ability) provided to the patient during therapy may influence
the patient’s perception of task difficulty, increase confidence for performing the
task, and enhance motor learning of the skill being practiced.
Strategies which support a person’s psychological need to have control of one’s
own behavior (i.e., Autonomy) have also demonstrated positive effects on the learn-
ing of motor skills. For example, Chiviacowsky et al. (2012b) showed that when in-
dividuals with Parkinson’s disease were practicing a balance task, the group provided
with the opportunity to choose which trials they would use a balance pole (i.e., self-
control) performed better on a retention test than the control group who was given the
pole by the experimenter. The two groups received the same number of practice trials
and the same number of trials with the pole, and in the same sequence across trials
(i.e., yoking procedure). The distinguishing feature that impacted the learning of this
skill was the fulfillment of autonomy (i.e., fundamental psychological need) afforded
to the self-control group (Chiviacowsky et al., 2012b). Finally, there is considerable
evidence that self-controlled conditions of practice (e.g., self-controlled feedback)
are better for learning than externally controlled conditions (Chiviacowsky et al.,
2012b; Lewthwaite and Wulf, 2010). Together, the behavioral evidence suggests that
supporting the learner’s autonomy by giving choices concerning aspects of the reha-
bilitation program or practice session (e.g., which trials to receive feedback about)
may be a fruitful direction for future work that seeks to drive positive plasticity and
optimize recovery.
Conditions that satisfy the individual’s basic need to relate to others (i.e., social
relatedness) have been shown to improve motor learning and recovery. Research
investigating the role of practicing in dyads shows beneficial effects on learning
(Granados and Wulf, 2007; Shea et al., 1999). For example, relative to individual
practice, young adults learning a novel balance task in pairs and given the opportu-
nity to interact with their partner during the practice showed more effective
performance during the acquisition period and retention tests 1 day later (Shea
et al., 1999).
Incorporating the strategies discussed in this section to address the patient’s fun-
damental psychological needs during therapy can optimize motor skill learning and
enhance recovery. The integration of these motivational perspectives into the reha-
bilitation approach will enable translation of important social-cognitive-behavioral
principles to advance clinical practice.
3477 Examples of promising new therapies
7.2 AN INTEGRATED MODEL: ACCELERATED SKILL ACQUISITION
PROGRAM
We developed an evidence-based intervention, the ASAP that integrates con-
temporary principles of motor learning (James et al., 2009; Lum et al., 2009;
Tretriluxana et al., 2013; Winstein et al., 2013b). ASAP is a combination of
task-specific and skill-based/impairment-mitigating training with embedded
patient-centered motivational enhancements. Targeted task-specific training (skill)
emerges as the single most important approach to intervention for the disabling
consequences of stroke in mildly to moderately impaired participants. The funda-
mental problems that ASAP addresses are conceived as the learning or relearning
of motor skills to optimally affect neural plasticity (Kleim, 2012) as well as skills
to self-direct posttraining activities (Sabini et al., 2013). Development of skill is
facilitated by the amelioration of impairments (e.g., muscle weakness, low self-
efficacy) to enhance capacity (Corti et al., 2012; Platz et al., 2005; Thielman
et al., 2004). Attention to motor learning, motor control (e.g., goal-directed whole
tasks with natural synergies in natural contexts) (Schmidt and Lee, 2011; Wu et al.,
2000), and basic exercise physiology (e.g., overload in terms of training load/
intensity, speed) principles is very relevant (Panarese et al., 2012). Social-
cognitive-psychological theories of motivation is applied in this intervention for
immediate and particularly longer-term participant engagement. These assume that
intrinsic sources of motivation, including perceptions of self-determination
(choice, control, collaboration) and self-efficacy (confidence in one’s capabilities)
are key contributors of continued choice, effort, and persistence to use paretic
limbs, which, in turn, leads to mitigation of disability and of self-imposed
participation restrictions. A note of historical interest, the ASAP intervention
draws upon research from motor learning and several overlapping fields of study
and, in fact, incorporates principles of even more subfields of movement science
(e.g., exercise physiology). As such, we do not consider ASAP as a motor learning
approach, per se (Chan et al., 2006).
7.2.1 Overlapping Constructs of Skill, Capacity, and Motivation
In this section, we outline the conceptual framework for ASAP. A pathway from
impairment reduction to functional capability to more general use of restored
limbs in natural contexts often is implicit but less frequently operationalized in
therapeutic practice. This conceptual model derives from the infusion of motor
learning, neuroscience, and behavioral science described earlier (Askim et al.,
2009; Bandura, 1997; Dancause and Nudo, 2011; Schmidt and Lee, 2011) with
the developing translational framework proposed in this chapter. Figure 2 illustrates
the conceptual framework that skill (motor learning and self-management), capac-
ity (impairment mitigation), and motivation (intrinsic drive) together form the
fundamental components for an effective rehabilitation program that is focused
on the person with the paretic limb instead of the paretic limb that is attached
to the person. These three essential elements result in a set of eight nonexclusive
348 CHAPTER 16 Translating the science into practice
principles that inform rehabilitation practice (Table 1). Activities to increase
capacity, skills, and motivation are centered on specific tasks of the participant’s
choosing. Here, the task is viewed as an important vehicle for the acquisition of
skilled movements, a means to promote capacity building, and as a mechanism
to foster the development of motivation for meaningful task engagement in the
natural setting. Table 1 lists the principles of ASAP along with implementation
examples.
The Interdisciplinary Comprehensive Arm Rehabilitation Evaluation (ICARE)
phase III, randomized controlled trial (Winstein et al., 2013b) is currently underway
at this writing. ICARE was developed to compare the effectiveness for paretic arm
recovery of the investigational intervention, ASAP, with a dose-matched usual care
group. It was designed with a relatively high dose of therapy in large part to ensure a
reasonable test of the intervention that is dependent on sufficient practice for skill
acquisition and generalizability beyond the clinic setting (i.e., 30 1-h visits distrib-
uted over 10 weeks delivered in the outpatient setting). Primary and secondary out-
comes from this trial are to be released during the first quarter of 2015. It is our
expectation that the ASAP principles would apply across a diverse spectrum of dis-
abling conditions to rehabilitation interventions for a number of different patient
groups and are not unique to the recovery of upper-extremity function in neurological
conditions.
Further refinement and testing of ASAP, and in varying populations and permu-
tations, in well-conceived and sound clinical research is encouraged (Dobkin, 2009;
Hart and Bagiella, 2012). Relative to most protocol-driven approaches (e.g., CIMT),
this principle-based approach was undertaken to provide for a more flexible, respon-
sive, and customizable intervention, including innovative technologies for partici-
pants of varying clinical needs, severity levels, and personal preferences for
therapeutic goals. The identification of multiple principles guiding dynamic clinical
decisions means that in any given moment, some principles will be emphasized,
Motivation
TASK
Skill
Capacity
FIGURE 2
Conceptual model for the accelerated skill acquisition program. Activities to increase
capacity, skill, and motivation are centered around meaningful tasks of the participant’s
choosing.
3497 Examples of promising new therapies
while others may be downplayed. However, it is most often the case that therapeutic
actions can satisfy one or more principles without contradicting others (Winstein
et al., 2014). It is expected that all of the principles will be supported over the course
of a therapy session and especially over a multisession episode of care. The ability to
take advantage of frequently occurring “teachable moments” in real time is one
strength of a principle-driven approach. Conversely, this abstraction and dynamic
flexibility can be challenging for inexperienced clinicians but exciting to those seek-
ing new challenges in their clinical practice and high-quality interactions with those
in their care.
Table 1 Principles of ASAP with implementation examples
Principle Implementation examples
1. Ensure challenging and meaningful
practice
Demonstrate the challenge threshold (the
performance threshold above which
movement breaks down and is
unsuccessful, and below which the task can
be accomplished relatively successfully)
Focus on skillful performance of important
activity to participant
2. Address important (interfering)
changeable impairments
Focus on mitigating a particular area of
weakness (e.g., wrist), pain, or interference
with progress
3. Enhance motor capacity through
overload and specificity
Practice at a clearly intense level
Provide task repetitions to physical limits
4. Preserve natural goal-directedness in
movement organization
Perform the natural task, practiced with
natural coordination demands
5. Avoid artificial task breakdowns when
possible
When feasible, practice the whole task in its
functional entirety
Break down the functional task when key to
pinpointing or addressing the problem area
6. Assure active patient/participant
involvement and opportunities for self-
direction
Encourage participant activity/response
involving problem solving or task
construction/determination
7. Balance immediate and future needs Participant problem solving (problem
identification, solution generation,
education, and action plan discussions
focused on future, action plan
extrapolations of session activities for home
practice/recovery); focus is on knowledge
and choices for the future
8. Drive task-specific self-confidence
high through performance
accomplishments
Assess participant’s task self-efficacy
Demonstrate progress through clear
measurement (timed performance, counts,
repetitions, increased weight, etc.)
Celebrate or attend to success
350 CHAPTER 16 Translating the science into practice
8OPPORTUNITIES AND CHALLENGES FOR FUTURE
TRANSLATIONAL RESEARCH
Despite the varied intervention options described above, a significant percentage of
individuals with suboptimal recovery of the paretic arm and hand are unable to main-
tain and generalize the gains achieved in therapy to the natural environment after
therapy ends (Hidaka et al., 2012; Takebayashi et al., 2013). It is estimated that
65% of patients at 6 months after stroke are unable to incorporate the paretic hand
effectively into daily activities (Dobkin, 2005; Mayo et al., 2002). This degree of
disability contributes to a reduced quality of life after stroke (Duncan et al., 2003;
Jonsson et al., 2005; Mayo et al., 2002; Suenkeler et al., 2002). The true extent of
disability has been underrepresented by measures that capture only basic activities
of daily living, such as self-care, or impairment level (e.g., Fugl–Meyer score) and do
not extend to valued activities and participation at higher levels of functioning that
are most affected by a residual upper-extremity disability (Dromerick et al., 2003;
Duncan et al., 2000; Kwon et al., 2004; Mahoney and Barthel, 1965; Mayo et al.,
2002; Winstein, 2004).
For stroke-affected upper limb recovery, the most significant outcome to the pa-
tient is the ability to voluntarily and spontaneously use the paretic arm and hand in
the natural environment for valued activities (Barker and Brauer, 2005; Barker et al.,
2007). From the patients’ perspective, paretic arm use is strongly associated with the
perception of overall recovery (Fritz et al., 2007). Importantly, greater engagement
in valued activities was found to be significantly associated with subsequent im-
provement in emotional well-being (Egan et al., 2014). The opportunity to tap the
motivational circuits in meaningful ways and in the context of evidence-based inter-
ventions is a challenge for the traditional clinical trialist. Once the rehabilitation
community accepts the importance of choosing primary outcomes from the quality
of life and participation domain of the International Classification of Functioning,
Disability and Health (WHO, 2001), it will represent a true paradigm shift in the
way clinical trials in neurorehabilitation are conceptualized, designed, and
implemented.
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360 CHAPTER 16 Translating the science into practice
... The global approach should take in consideration the patient's perspectives and wills, reinforcing positive emotional aspects, intrinsic motivation, and reward. Indeed, since motivation enhances motor learning, practice need to be salient and meaningful for optimal engagement and results [133,134]. In this context, the patient is actively involved as her/his training is her/his responsibility. ...
... These include the ability to make realistic plans, a positive self-confidence, proper skills for communication and problem-solving, an emotional intelligence, appropriate care and support, and a positive self-image [2,139]. When the individual's needs are considered in the context of instructions or expectations, the learning/rehabilitation process is significantly accelerated [134]. ...
... Extending skills beyond the context of therapy is crucial in a truly tailored, patient-centered program. This reinforces the gains for "real life" through a virtuous cycle that is more easily assimilated by the patient and self-sustained [2,134]. ...
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Neurological disorders often cause severe long-term disabilities with substantial activity limitations and participation restrictions such as community integration, family functioning, employment, social interaction and participation. Increasing understanding of brain functioning has opened new perspectives for more integrative interventions, boosting the intrinsic central nervous system neuroplastic capabilities in order to achieve efficient behavioral restitution. Neurorehabilitation must take into account the many aspects of the individual through a comprehensive analysis of actual and potential cognitive, behavioral, emotional and physical skills, while increasing awareness and understanding of the new self of the person being dealt with. The exclusive adoption by the rehabilitator of objective functional measures often overlooks the values and goals of the disabled person. Indeed, each individual has their own rhythm, unique life history and personality construct. In this challenging context, it is essential to deepen the assessment through subjective measures, which more adequately reflect the patient’s perspective in order to shape genuinely tailored instead of standardized neurorehabilitation approaches. In this overly complex panorama, where confounding and prognostic factors also strongly influence potential functional recovery, the healthcare community needs to rethink neurorehabilitation formats.
... Such situation is highly problematic as, to the best of our knowledge, there is no evidence of recovery in either the movement pattern coordination or in their rigidity given any proposed intervention (Scrivener et al., 2020;Winstein & Kay, 2015). Most of current interventions are restricted to compensations in movement patterns to improve movement outcome (e.g., step length, symmetry, walking speed). ...
... Third, the task is organized to address essential biomechanical components (e.g., hip flexion in stair climbing). Fourth, despite supporting given biomechanical aspects, the therapy organizes the environment and task as to support active search for new motor solutions in practice (Winstein & Kay, 2015). That is, a given solution is not imposed to the system affording proactive problem-solving. ...
... An important principle in rehabilitation is that practice should be progressive and optimally tailored to the individual's capabilities (Van Vliet and Wulf, 2006;Kleim and Jones, 2008;Langhorne et al., 2009;Winstein and Kay, 2015). In conventional post-stroke rehabilitation, the therapist provides verbal and visual feedback, and typically uses hands-on demonstration (Hartveld and Hegarty, 1996;Ballinger et al., 1999;DeJong et al., 2004;Wohlin Wottrich et al., 2004). ...
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Providing effective feedback to patients in a rehabilitation training program is essential. As technologies are being developed to support patient training, they need to be able to provide the users with feedback on their performance. As there are various aspects on which feedback can be given (e.g., task success and presence of compensatory movements), it is important to ensure that users are not overwhelmed by too much information given too frequently by the assistive technology. We created a rule-based set of guidelines for the desired hierarchy, timing, and content of feedback to be used when stroke patients train with an upper-limb exercise platform which we developed. The feedback applies to both success on task completion and to the execution of compensatory movements, and is based on input collected from clinicians in a previous study. We recruited 11 stroke patients 1–72 months from injury onset. Ten participants completed the training; each trained with the rehabilitation platform in two configurations: with motor feedback (MF) and with no motor feedback (control condition) (CT). The two conditions were identical, except for the feedback content provided: in both conditions they received feedback on task success; in the MF condition they also received feedback on making undesired compensatory movements during the task. Participants preferred the configuration that provided feedback on both task success and quality of movement (MF). This pilot experiment demonstrates the feasibility of a system providing both task-success and movement-quality feedback to patients based on a decision tree which we developed.
... Based on a weekly telephone conversation with the occupational therapist, they are asked to enter a jointly agreed weekly goal and desired number of repetitions, the actual number of repetitions, daily exercise duration and evaluate how they fared with the individual exercises and finally, their overall satisfaction and (self-)management in the logbook. The intervention will involve an individualised, taskoriented home exercise programme oriented on motor learning and task-specific exercise programmes for PaS [41][42][43][44][45][46][47] and on the principles of the OPTIMAL theory (table 1), delivered either video-based (Video group) or paper-based (Paper group). The intervention will be offered by an experienced occupational therapist (MW) as an add-on to usual outpatient rehabilitation and performed six times per week, 50 min per session for 4 weeks. ...
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... We refer to this phenomenon as neural plasticity. Research into neurorehabilitation is now providing insights, making it possible to develop guidelines for effective neurorehabilitation based on optimizing neural plasticity, which can be tailored to the needs and possibilities of the individual (7)(8)(9). The many factors for achieving the optimal neurorehabilitation should all be considered when designing a training schedule for an individual with a neurological disorder, but some are more difficult to include than others are, during personal rehabilitation training in the clinic. ...
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Background: Effective science-based motor rehabilitation requires high volume of individualized, intense physical training, which can be difficult to achieve exclusively through physical 1-on-1 sessions with a therapist. Home-based training, enhanced by technological solutions, could be a tool to help facilitate the important factors for neuroplastic motor improvements. Objectives: This review aimed to discover how the inclusion of modern information and communications technology in home-based training programs can promote key neuroplastic factors associated with motor learning in neurological disabilities and identify which challenges are still needed to overcome. Methods: We conducted a thorough literature search on technological home-based training solutions and categorized the different fundamental approaches that were used. We then analyzed how these approaches can be used to promote certain key factors of neuroplasticity and which challenges still need to be solved or require external personalized input from a therapist. Conclusions: The technological approaches to home-based training were divided into three categories: sensory stimuli training, digital exchange of information training, and telerehabilitation. Generally, some technologies could be characterized as easily applicable, which gave the opportunity to promote flexible scheduling and a larger overall training volume, but limited options for individualized variation and progression. Other technologies included individualization options through personalized feedback that might increase the training effect, but also increases the workload of the therapist. Further development of easily applicable and intelligent solutions, which can return precise feedback and individualized training suggestions, is needed to fully realize the potential of home-based training in motor learning activities.
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Motivational influence on bradykinesia in Parkinson's disease may be observed in situations of emotional and physical stress, a phenomenon known as paradoxical kinesis. However, little is known about motivational modulation of movement speed beyond these extreme circumstances. In particular, it is not known if motivational factors affect movement speed by improving movement preparation/initiation or execution (or both) and how this effect relates to the patients' medication state. In the present study, we tested if provision of motivational incentive through monetary reward would speed-up movement initiation and/or execution in Parkinson's disease patients and if this effect depended on dopaminergic medication. We studied the effect of monetary incentive on simple reaction time in 11 Parkinson's disease patients both "off" and "on" dopaminergic medication and in 11 healthy participants. The simple reaction time task was performed across unrewarded and rewarded blocks. The initiation time and movement time were quantified separately. Anticipation errors and long responses were also recorded. The prospect of reward improved initiation times in Parkinson's disease patients both "off" and "on" dopaminergic medication, to a similar extent as in healthy participants. However, for "off" medication, this improvement was associated with increased frequency of anticipation errors, which were eliminated by dopamine replacement. Dopamine replacement had an additional, albeit small effect, on reward-related improvement of movement execution. Motivational strategies are helpful in overcoming bradykinesia in Parkinson's disease. Motivational factors may have a greater effect on bradykinesia when patients are "on" medication, as dopamine appears to be required for overcoming speed-accuracy trade-off and for improvement of movement execution. Thus, medication status should be an important consideration in movement rehabilitation programmes for patients with Parkinson's disease.
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Unlabelled: : This special interest article provides a historical framework with a contemporary case example that traces the infusion of the science of motor learning into neurorehabilitation practice. The revolution in neuroscience provided the first evidence for learning-dependent neuroplasticity and presaged the role of motor learning as critical for restorative therapies after stroke. The scientific underpinnings of motor learning have continued to evolve from a dominance of cognitive or information processing perspectives to a blend with neural science and contemporary social-cognitive psychological science. Furthermore, advances in the science of behavior change have contributed insights into influences on sustainable and generalizable gains in motor skills and associated behaviors, including physical activity and other recovery-promoting habits. For neurorehabilitation, these insights have tremendous relevance for the therapist-patient interactions and relationships. We describe a principle-based intervention for neurorehabilitation termed the Accelerated Skill Acquisition Program that we developed. This approach emphasizes integration from a broad set of scientific lines of inquiry including the contemporary fields of motor learning, neuroscience, and the psychological science of behavior change. Three overlapping essential elements-skill acquisition, impairment mitigation, and motivational enhancements-are integrated. Video abstract available: (See Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A71) for more insights from the authors.
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Francis S. Collins and Lawrence A. Tabak discuss initiatives that the US National Institutes of Health is exploring to restore the self-correcting nature of preclinical research. A growing chorus of concern, from scientists and laypeople, contends that the complex system for ensuring the reproducibility of biomedical research is failing and is in need of restructuring 1,2 . As leaders of the US National Institutes of Health (NIH), we share this concern and here explore some of the significant interventions that we are planning. Science has long been regarded as ‘self-correcting’, given that it is founded on the replication of earlier work. Over the long term, that principle remains true. In the shorter term, however, the checks and balances that once ensured scientific fidelity have been hobbled. This has compromised the ability of today’s researchers to reproduce others’ findings.