- We review investigations of whether tDCS can facilitate motor skill learning and adaptation.
- We identify several caveats in the existing literature and propose solutions for addressing these.
- Open Science efforts will improve standardization, reproducibility and quality of future research.
Posts Tagged Learning
[ARTICLE] Changes in actual arm-hand use in stroke patients during and after clinical rehabilitation involving a well-defined arm-hand rehabilitation program: A prospective cohort study – Full Text
Improvement of arm-hand function and arm-hand skill performance in stroke patients is reported by many authors. However, therapy content often is poorly described, data on actual arm-hand use are scarce, and, as follow-up time often is very short, little information on patients’ mid- and long-term progression is available. Also, outcome data mainly stem from either a general patient group, unstratified for the severity of arm-hand impairment, or a very specific patient group.
To investigate to what extent the rate of improvement or deterioration of actual arm-hand use differs between stroke patients with either a severely, moderately or mildly affected arm-hand, during and after rehabilitation involving a well-defined rehabilitation program.
Design: single–armed prospective cohort study. Outcome measure: affected arm-hand use during daily tasks (accelerometry), expressed as ‘Intensity-of arm-hand-use’ and ‘Duration-of-arm-hand-use’ during waking hours. Measurement dates: at admission, clinical discharge and 3, 6, 9, and 12 months post-discharge. Statistics: Two-way repeated measures ANOVAs.
Seventy-six patients (63 males); mean age: 57.6 years (sd:10.6); post-stroke time: 29.8 days (sd:20.1) participated. Between baseline and 1-year follow-up, Intensity-of-arm-hand-use on the affected side increased by 51%, 114% and 14% (p < .000) in the mildly, moderately and severely affected patients, respectively. Similarly, Duration-of-arm-hand-use increased by 26%, 220% and 161% (p < .000). Regarding bimanual arm-hand use: Intensity-of-arm-hand-use increased by 44%, 74% and 30% (p < .000), whereas Duration-of-arm-hand-use increased by 10%, 22% and 16% (p < .000).
Stroke survivors with a severely, moderately or mildly affected arm-hand showed different, though (clinically) important, improvements in actual arm-hand use during the rehabilitation phase. Intensity-of-arm-hand-use and Duration-of-arm-hand-use significantly improved in both unimanual and bimanual tasks/skills. These improvements were maintained until at least 1 year post-discharge.
After stroke, the majority of stroke survivors experiences significant arm-hand impairments [1, 2] and a decreased use of the paretic arm and hand in daily life . The actual use of the affected hand in daily life performance depends on the severity of the arm-hand impairment [4–6] and is associated with perceived limitations in participation [7, 8]. Severity of arm-hand impairment is also associated with a decrease of health-related quality of life , restricted social participation , and subjective well-being [11, 12].
Numerous interventions and arm-hand rehabilitation programs have been developed in order to resolve arm-hand impairments in stroke patients [6, 13]. In the Netherlands, a number of stroke units in rehabilitation centres implemented a well-described ‘therapy-as-usual’ arm-hand rehabilitation program, called CARAS (acronym for: Concise Arm and hand Rehabilitation Approach in Stroke), serving a broad spectrum of stroke patients across the full stroke severity range of arm-hand impairments. The arm-hand rehabilitation program has been developed to guide clinicians in systematically designing arm-hand rehabilitation, tailored towards the individual patient’s characteristics while keeping control over the overall heterogeneity of this population typically seen in stroke rehabilitation centres. A vast majority of stroke patients who participated in CARAS improved on arm-hand function (AHF), on arm-hand skilled performance (AHSP) capacity and on (self-) perceived performance, both during and after clinical rehabilitation . The term ‘arm-hand function’ (AHF) refers to the International Classification of Functioning (ICF)  ‘body function and structures level’. The term ‘arm-hand skilled performance’ (AHSP) refers to the ICF ‘activity level’, covering capacity as well as both perceived performance and actual arm-hand use .
Improved AHF and/or AHSP capacity do not automatically lead to an increase in actual arm-hand use and do not guarantee an increase of performing functional activities in daily life [18–20]. Improvements at function level, i.e. regaining selectivity, (grip) strength and/or grip performance, do not automatically lead to improvements experienced in real life task performance of persons in the post-stroke phase who live at home [18, 21]. Next to outcome measures regarding AHF, AHSP capacity and (self-) perceived AHSP, which are typically measured in controlled conditions, objective assessment of functional activity and actual arm-hand use outside the testing situation is warranted [22, 23].
Accelerometry can be used to reliably and objectively assess actual arm-hand use during daily task performance [24–32]and has been used in several studies to detect arm-hand movements and evaluate arm-hand use in the post-stroke phase [20, 33–35]. Previous studies have demonstrated that, in stroke patients, movement counts, as measured with accelerometers, are associated with the use of the affected arm-hand (Motor Activity Log score) [36, 37] and, at function level, with the Fugl-Meyer Assessment . Next to quantifying paretic arm-hand use, accelerometers have also been used to provide feedback to further enhance the use of the affected hand in home-based situations . Most studies consist of relatively small [27, 30, 40–44] and highly selected study populations  with short time intervals between baseline and follow-up measurements. As to our knowledge, only a few studies monitored arm-hand use in stroke patients for a longer period, i.e. between time of discharge to a home situation or till 6 to 12 months after stroke [19, 44, 46]. However, they used a relatively small study sample and their intervention aimed at arm-hand rehabilitation was undefined. Both studies of Connell et al. and Uswatte et al. describe a well-defined arm hand intervention where accelerometry data were used as an outcome measure [27, 47]. However, the study population described by Connell et al. consisted of a relative small and a relative mildly impaired group of chronic stroke survivors. The study population described by Uswatte et al. consisted of a large group of sub-acute stroke patients within strict inclusion criteria ranges , who, due to significant spontaneous neurologic recovery within this sub-acute phase, had a mildly impaired arm and hand [48, 49]. This means that the group lacked persons with a moderately to severely affected arm-hand, who are commonly treated in the daily rehabilitation setting.
The course of AHF and AHSP of a broad range of sub-acute stroke patients during and after rehabilitation involving a well-defined arm-hand rehabilitation program (i.e. CARAS)  has been reported by Franck et al. . The present paper provides data concerning actual arm-hand use in the same study population, and focuses on two objectives. The first aim is to investigate changes in actual arm-hand use across time, i.e. during and after clinical rehabilitation, within a stroke patient group typically seen in daily medical rehabilitation practice, i.e. covering a broad spectrum of arm-hand problem severity levels, who followed a well-described arm-hand treatment regime. The second aim is to investigate to what extent improvement (or deterioration) regarding the use of the affected arm-hand in daily life situations differs between patient categories, i.e. patients with either a severely, moderately or mildly impaired arm-hand, during and after their rehabilitation, involving a well-defined arm-hand rehabilitation program.[…]
[BLOG POST] Where does the controversial finding that adult human brains don’t grow new neurons leave ongoing research?
Scientists have known for about two decades that some neurons – the fundamental cells in the brain that transmit signals – are generated throughout life. But now a controversial new study from the University of California, San Francisco, casts doubt on whether many neurons are added to the human brain after birth.
As a translational neuroscientist, this work immediately piqued my interest. It has direct implications for the research my lab does: We transplant young neurons into damaged brain areas in mice in an attempt to treat epileptic seizures and the damage they’ve caused. Like many labs, part of our work is based on a foundational belief that the hippocampus is a brain region where new neurons are born throughout life.
If the new study is right, and human brains for the most part don’t add new neurons after infancy, researchers like me need to reconsider the validity of the animal models we use to understand various brain conditions – in my case temporal lobe epilepsy. And I suspect other labs that focus on conditions including drug addiction, depression and post-traumatic stress disorder are thinking about what the UCSF study means for their investigations, too.
When and where are new neurons born?
No doubt, the adult human brain is able to learn throughout life and to change and adapt – a capability brain scientists call neuroplasticity, the brain’s ability to reorganize itself by rewiring connections. Yet, a central dogma in the field of neuroscience for nearly 100 years had been that a child is born with all the neurons she will ever have because the adult brain cannot regenerate neurons.
Just over half a century ago, researchers devised a way to study proliferation of cells in the mature brain, based on techniques to incorporate a radioactive label into new cells as they divide. This approach led to the startling discovery in the 1960s that rodent brains actually could generate new neurons.
Neurogenesis – the production of new neurons – was previously thought to only occur during embryonic life, a time of extremely rapid brain growth and expansion, and the rodent findings were met with considerable skepticism. Then researchers discovered that new neurons are also born throughout life in the songbird brain, a species scientists use as a model for studying vocal learning. It started to look like neurogenesis plays a key role in learning and neuroplasticity – at least in some brain regions in a few animal species.
Even so, neuroscientists were skeptical that many nerve cells could be renewed in the adult brain; evidence was scant that dividing cells in mammalian brains produced new neurons, as opposed to other cell types. It wasn’t until researchers extracted neural stem cells from adult mouse brains and grew them in cell culture that scientists showed these precursor cells could divide and differentiate into new neurons. Now it is generally well accepted that neurogenesis takes place in two areas of the adult rodent brain: the olfactory bulbs, which process smell information, and the hippocampus, a region characterized by neuroplasticity that is required for forming new declarative memories.
Adult neural stem cells cluster together in what scientists call niches – hotbeds for cultivating the birth and growth of new neurons, recognizable by their distinctive architecture. Despite the mounting evidence for regional growth of new neurons, these studies underscored the point that the adult brain harbors only a few stem cell niches and their capacity to produce neurons is limited to just a few types of cells.
With this knowledge, and new tools for labeling proliferating cells and identifying maturing neurons, scientists began to look for postnatal neurogenesis in primate and human brains.
What’s happening in adult human brains?
Many neuroscientists believe that by understanding the process of adult neurogenesis we’ll gain insights into the causes of some human neurological disorders. Then the next logical step would be trying to develop new treatments harnessing neurogenesis for conditions such as Alzheimer’s disease or trauma-induced epilepsy. And stimulating resident stem cells in the brain to generate new neurons is an exciting prospect for treating neurodegenerative diseases.
Because neurogenesis and learning in rodents increases with voluntary exercise and decreases with age and early life stress, some workers in the field became convinced that older people might be able to enhance their memory as they age by maintaining a program of regular aerobic exercise.
However, obtaining rigorous proof for adult neurogenesis in the human and primate brain has been technically challenging – both due to the limited experimental approaches and the larger sizes of the brains, compared to reptiles, songbirds and rodents.
Researchers injected a compound found in DNA, nicknamed BrdU to identify brand new neurons in human adult hippocampus – but the labeled cells were extremely rare. Other groups demonstrated that adult human brain tissue obtained during neurosurgery contained stem cell niches that housed progenitor cells that could generate new neurons in the lab, showing that these cells had an inborn neurogenic capacity, even in adults.
But even when scientists saw evidence for new neurons in the brain, they tended to be scarce. Some neurogenesis experts were skeptical that evidence based on incorporating BrdU into DNA was a reliable method for proving that new cells were actually being born through cell division, rather than just serving as a marker for other normal cell functions.
Further questions about how long human brains retain the capacity for neurogenesis arose in 2011, with a study that compared numbers of newborn neurons migrating in the olfactory bulbs of infants versus older individuals up to 84 years of age. Strikingly, in the first six months of life, the baby brains contained lots of chains of young neurons migrating into the frontal lobes, regions that guide executive function, long-range planning and social interactions. These areas of the human cortex are hugely increased in size and complexity compared to rodents and other species. But between 6 to 18 months of age, the migrating chains dwindled to a thin stream. Then, a very different pattern emerged: Where the migrating chains of neurons had been in the infant brain, a cell-free gap appeared, suggesting that neural stem cells become depleted during the first six months of life.
Questions still lingered about the human hippocampus and adult neurogenesis as a source for its neuroplasticity. One group came up with a clever approach based on radiocarbon dating. They measured how much atmospheric ¹⁴C – a radioactive isotope derived from nuclear bomb tests – was incorporated into people’s DNA. This method suggested that as many as 700 new cells are added to the adult human hippocampus every day. But these findings were contradicted by a 2016 study that found that the neurogenic cells in the adult hippocampus could only produce non-neuronal brain cells called microglia.
Rethinking neurogenesis research
Now the largest and most comprehensive study conducted to date presents even stronger evidence that robust neurogenesis doesn’t continue throughout adulthood in the human hippocampus – or if it does persist, it is extremely rare. This work is controversial and not universally accepted. Critics have been quick to cast doubt on the results, but the finding isn’t totally out of the blue.
So where does this leave the field of neuroscience? If the UCSF scientists are correct, what does that mean for ongoing research in labs around the world?
Because lots of studies of neurological diseases are done in mice and rats, many scientists are invested in the possibility that adult neurogenesis persists in the human brain, just as it does in rodents. If it doesn’t, how valid is it to think that the mechanisms of learning and neuroplasticity in our model animals are comparable to those in the human brain? How relevant are our models of neurological disorders for understanding how changes in the hippocampus contribute to disorders such as the type of epilepsy I study?
In my lab, we transplant embryonic mouse or human neurons into the adult hippocampus in mice, after damage caused by epileptic seizures. We aim to repair this damage and suppress seizures by seeding the mouse hippocampus with neural stem cells that will mature and form new connections. In temporal lobe epilepsy, studies in adult rodents suggest that naturally occurring hippocampal neurogenesis is problematic. It seems that the newborn hippocampal neurons become highly excitable and contribute to seizures. We’re trying to inhibit these newborn hyperexcitable neurons with the transplants. But if humans don’t generate new hippocampal neurons, then maybe we’re developing a treatment in mice for a problem that has a different mechanism in people.
Perhaps our species has evolved separate mechanisms for neuroplasticity, distinct from those used by species such as rats and mice. One possibility is that there are other sites in the human brain where neurogenesis occurs – its a big structure and more exploration will be necessary. If it turns out to be true that the human brain has a diminished capacity for neurogenesis after birth, the finding will have important implications for how neuroscientists like me think about tackling brain disorders.
Perhaps most importantly, this work underscores how crucial it is to learn how to increase the longevity of the neurons we do have, born early in life, and how we might replace or repair neurons that become damaged.
[ARTICLE] Reorganization of finger coordination patterns through motor exploration in individuals after stroke – Full Text
Impairment of hand and finger function after stroke is common and affects the ability to perform activities of daily living. Even though many of these coordination deficits such as finger individuation have been well characterized, it is critical to understand how stroke survivors learn to explore and reorganize their finger coordination patterns for optimizing rehabilitation. In this study, I examine the use of a body-machine interface to assess how participants explore their movement repertoire, and how this changes with continued practice.
Ten participants with chronic stroke wore a data glove and the finger joint angles were mapped on to the position of a cursor on a screen. The task of the participants was to move the cursor back and forth between two specified targets on a screen. Critically, the map between the finger movements and cursor motion was altered so that participants sometimes had to generate coordination patterns that required finger individuation. There were two phases to the experiment – an initial assessment phase on day 1, followed by a learning phase (days 2–5) where participants trained to reorganize their coordination patterns.
Participants showed difficulty in performing tasks which had maps that required finger individuation, and the degree to which they explored their movement repertoire was directly related to clinical tests of hand function. However, over four sessions of practice, participants were able to learn to reorganize their finger movement coordination pattern and improve their performance. Moreover, training also resulted in improvements in movement repertoire outside of the context of the specific task during free exploration.
Stroke survivors show deficits in movement repertoire in their paretic hand, but facilitating movement exploration during training can increase the movement repertoire. This suggests that exploration may be an important element of rehabilitation to regain optimal function.
Stroke often results in impairments of upper extremity, including hand and finger function, with 75% of stroke survivors facing difficulties performing activities of daily living [1, 2]. Critically, impairments after stroke not only include muscle- and joint-specific deficits such as weakness, and changes in the kinetic and kinematic workspace of the fingers [3, 4], but also coordination deficits such as reduced independent joint control  and impairments in finger individuation and enslaving [6, 7, 8, 9]. Therefore, understanding how to address these coordination deficits is critical for improving hand rehabilitation.
Typical approaches to hand rehabilitation emphasize repetition  and functional practice based on evidence that such experience can cause reorganization in the brain . Although this has proven to be reasonably successful, functional practice (such as repetitive grasping of objects) does not specify the coordination pattern to be used when performing the tasks. As a result, because of the redundancy in the human body, there is a risk that stroke survivors may adopt atypical compensatory movements to perform tasks . These compensatory movements have been mainly identified during reaching [13, 14], but there is evidence that they are also present in finger coordination patterns during grasping . Although there is still debate over the role of compensatory movements in rehabilitation , there is at least some evidence both in animal and humans that continued use of these compensatory patterns may be detrimental to true recovery [17, 18, 19].
To address this issue, there has been a greater focus on directly facilitating the learning of new coordination patterns. Specifically, in hand rehabilitation, virtual tasks (such as playing a virtual piano) have been examined as a way to train finger individuation [20, 21]. In these protocols, individuation is encouraged by asking participants to press a particular key with a finger, while keeping other fingers stationary. A similar approach to improve hand dexterity was also adopted by developing a glove that could be used as a controller for a popular guitar-playing video game . However, directly instructing desired coordination patterns to be produced becomes challenging as the number of degrees of freedom involved in the coordination pattern increase. For example, the hand has approximately 20 kinematic degrees of freedom, and providing verbal, visual or auditory feedback for simultaneously controlling all these degrees of freedom would be a major challenge. A potential solution that has been suggested is not to directly instruct the coordination pattern itself, but rather let participants explore different coordination patterns . This idea of motor exploration is based on dynamical systems theory that suggests that variability and exploration may help participants escape sub-optimal pre-existing coordination patterns and potentially settle in more optimal coordination patterns [24, 25, 26, 27]. Such exploration has been shown to be important in adapting existing movement repertoire , and has also been shown to be associated with faster rates of learning .
In order to test the hypothesis that exploration of novel coordination patterns can improve overall movement repertoire, I used a body-machine interface [30, 31] to examine how stroke survivors explore and reorganize finger coordination patterns with practice. A body-machine interface maps body movements (in this case finger movements) to the control of a real or virtual object (in this case a screen cursor), which can provide a way to elicit different coordination patterns in the context of an intuitive task. Specifically I examined: (i) how stroke survivors reorganize their finger coordination patterns, (ii) how training to explore novel coordination patterns affects their ability to reorganize their coordination pattern, and (iii) if training to explore novel coordination patterns has an effect on their overall movement repertoire. In this context, I use the term “novel” to indicate coordination patterns that require finger individuation. This assumption is motivated by the finding that stroke survivors have difficulty producing finger individuation even under explicit instruction [6, 9], and therefore it is highly likely that they would not use coordination patterns requiring finger individuation frequently in activities of daily living.[…]
[Abstract] Effects of tDCS on motor learning and memory formation: a consensus and critical position paper – Clinical Neurophysiology
Motor skills are required for activities of daily living. Transcranial direct current stimulation (tDCS) applied in association with motor skill learning has been investigated as a tool for enhancing training effects in health and disease. Here, we review the published literature investigating whether tDCS can facilitate the acquisition, retention or adaptation of motor skills. Work in multiple laboratories is underway to develop a mechanistic understanding of tDCS effects on different forms of learning and to optimize stimulation protocols. Efforts are required to improve reproducibility and standardization. Overall, reproducibility remains to be fully tested, effect sizes with present techniques vary over a wide range, and the basis of observed inter-individual variability in tDCS effects is incompletely understood. It is recommended that future studies explicitly state in the Methods the exploratory (hypothesis-generating) or hypothesis-driven (confirmatory) nature of the experimental designs. General research practices could be improved with prospective pre-registration of hypothesis-based investigations, more emphasis on the detailed description of methods (including all pertinent details to enable future modeling of induced current and experimental replication), and use of post-publication open data repositories. A checklist is proposed for reporting tDCS investigations in a way that can improve efforts to assess reproducibility.
[Abstract] Neural plasticity during motor learning with motor imagery practice: Review and perspectives
• TMS reveals the neural aspects of motor learning with MI.
• Neural plasticity during MI practice may occur at the cortical and spinal level.
• MI training may strengthen synapse efficiency.
• Presynaptic inhibition may decrease after MI training.
In the last decade, many studies confirmed the benefits of mental practice with motor imagery. In this review we first aimed to compile data issued from fundamental and clinical investigations and to provide the key-components for the optimization of motor imagery strategy. We focused on transcranial magnetic stimulation studies, supported by brain imaging research, that sustain the current hypothesis of a functional link between cortical reorganization and behavioral improvement. As perspectives, we suggest a model of neural adaptation following mental practice, in which synapse conductivity and inhibitory mechanisms at the spinal level may also play an important role.
[Abstract] Physiotherapists use a great variety of motor learning options in neurological rehabilitation, from which they choose through an iterative process: a retrospective think-aloud study.
Implications for Rehabilitation
The study provided insight into the way experienced therapist handle the great variety of possible motor learning options, including concrete ideas on how to operationalize these options in specific situations.
Despite differences in patients’ abilities, it seems that therapists use the same underlying clinical reasoning process when choosing a particular motor learning option.
Participating physiotherapists used more than the in guidelines suggested motor learning options and considered more than the suggested factors, hence adding practice based options of motor learning to the recommended ones in the guidelines.
A think-aloud approach can be considered for peer-to-peer and student coaching to enhance discussion on the motor learning options applied and the underlying choices and to encourage research by practicing clinicians.
Source: Physiotherapists use a great variety of motor learning options in neurological rehabilitation, from which they choose through an iterative process: a retrospective think-aloud study – Disability and Rehabilitation –
[ARTICLE] Revisiting the neurofunctional approach: Conceptualizing the core components for the rehabilitation of everyday living skills. – Full Text HTML
Background: Introduced in the 1980s, the neurofunctional approach (NFA) is one of the few interventions designed primarily for clients with severe deficits following traumatic brain injury (TBI). Specifically the NFA was intended for those individuals who were limited in their ability to solve novel problems or generalize skills from one setting to another and whose lack of insight limited their engagement in the rehabilitative process.
Description of the approach: The NFA is a client-centred, goal-driven approach that incorporates the principles of skill learning and promotes the development of routines and competencies in practical activities required for everyday living. Programmes based on the NFA are developed specifically to meet each client’s unique needs, using a range of evidence-based interventions.
Recent evidence: Recently the NFA has been found to be more effective than cognitive-retraining for some individuals with moderate-to-severe TBI who have deficits in activities of daily living. This paper aims to define the core features of the NFA, outline the theoretical basis on which it is founded and consider implications of the findings for rehabilitation after TBI in general. The NFA is highly relevant for clients living in the community who require a case manager to direct an integrated, rehabilitation programme or provide structured input for the long-term maintenance of skills.
Neuroplasticity is critical for learning, memory, and recovery of lost function following neurological damage. Noninvasive brain stimulation (NIBS) techniques can induce neuroplastic changes in the human cortex that are behaviorally relevant, raising the exciting possibility that these techniques might be therapeutically beneficial for neurorehabilitation following brain injury. However, the short duration and instability of induced effects currently limits their usefulness.
To date, trials investigating the therapeutic value of neuroplasticity-inducing NIBS have used either single or multiple treatment sessions, typically repeated once-daily for 1 to 2 weeks. Although multiple stimulation sessions are presumed to have cumulative effects on neuroplasticity induction, there is little direct scientific evidence to support this “once-daily” approach. In animal models, the repeated application of stimulation protocols spaced using relatively short intervals (typically of the order of minutes) induces long-lasting and stable changes in synaptic efficacy. Likewise, learning through spaced repetition facilitates the establishment of long-term memory. In both cases, the spacing interval is critical in determining the outcome.
Emerging evidence in healthy human populations suggests that the within-session spacing of NIBS protocols may be an effective approach for significantly prolonging the duration of induced neuroplastic changes. Similar to findings in the animal and learning literature, the interval at which spaced NIBS is applied seems to be a critical factor influencing the neuroplastic response. In this Point of View article, we propose that to truly exploit the therapeutic opportunities provided by NIBS, future clinical trials should consider the optimal spacing interval for repeated applications.
Upper limb extremity rehabilitation practices are increasingly involving robotic interaction for repetitive practice, and there is growing skepticism whether such systems can provide the relevant practice that can be generalized (or transferred) to functional activities in the real world.
Most importantly, will patients be able to generalize in three critical ways: (1) to unpracticed directions, (2) to unpracticed movement distances, and (3) to unpracticed weight-eliminated conditions? Rather than presuming that patients could generalize in three conditions, this study tested multiple hypotheses to see if there was any evidence of such generalization ability in healthy individuals.
We found that there was some evidence in all conditions except for the ability of healthy subjects to generalize to large movements after practicing small. Such results suggest that larger robotic systems are advantageous for training functional motions” that would not be possible with smaller systems …