Annette Sterr

Mobile EEG and its potential to promote the theory and application of imagery-based motor rehabilitation

Studying the brain in its natural state remains a major challenge for neuroscience. Solving this challenge would not only enable the refinement of cognitive theory, but also provide a better understanding of cognitive function in the type of complex and unpredictable situations that constitute daily life, and which are often disturbed in clinical populations. With mobile EEG, researchers now have access to a tool that can help address these issues. In this paper we present an overview of technical advancements in mobile EEG systems and associated analysis tools, and explore the benefits of this new technology. Using the example of motor imagery (MI) we will examine the translational potential of MI-based neurofeedback training for neurological rehabilitation and applied research.

Multimodal imaging of mild traumatic brain injury and persistent postconcussion syndrome

Persistent postconcussion syndrome (PCS) occurs in around 5–10% of individuals after mild traumatic brain injury (mTBI), but research into the underlying biology of these ongoing symptoms is limited and inconsistent. One reason for this could be the heterogeneity inherent to mTBI, with individualized injury mechanisms and psychological factors. A multimodal imaging study may be able to characterize the injury better.

Modulation of Total Sleep Time by Transcranial Direct Current Stimulation (tDCS)

Arousal and sleep are fundamental physiological processes, and their modulation is of high clinical significance. This study tested the hypothesis that total sleep time (TST) in humans can be modulated by the non-invasive brain stimulation technique transcranial direct current stimulation (tDCS) targeting a ‘top-down’ cortico-thalamic pathway of sleep-wake regulation. Nineteen healthy participants underwent a within-subject, repeated-measures protocol across five nights in the sleep laboratory with polysomnographic monitoring (adaptation, baseline, three experimental nights). tDCS was delivered via bi-frontal target electrodes and bi-parietal return electrodes before sleep (anodal ‘activation’, cathodal ‘deactivation’, and sham stimulation). Bi-frontal anodal stimulation significantly decreased TST, compared with cathodal and sham stimulation. This effect was location specific. Bi-frontal cathodal stimulation did not significantly increase TST, potentially due to ceiling effects in good sleepers. Exploratory resting-state EEG analyses before and after the tDCS protocols were consistent with the notion of increased cortical arousal after anodal stimulation and decreased cortical arousal after cathodal stimulation. The study provides proof-of-concept that TST can be decreased by non-invasive bi-frontal anodal tDCS in healthy humans. Further elucidating the ‘top-down’ pathway of sleep-wake regulation is expected to increase knowledge on the fundamentals of sleep-wake regulation and to contribute to the development of novel treatments for clinical conditions of disturbed arousal and sleep.

Polysomnographic Characteristics of Sleep in Stroke: A Systematic Review and Meta-Analysis

Background Research on sleep after stroke has focused mainly on sleep disordered breathing. However, the extend to which sleep physiology is altered in stroke survivors, how these alterations compare to healthy volunteers, and how sleep changes might affect recovery as well as physical and mental health has yet to be fully researched. Motivated by the view that a deeper understanding of sleep in stroke is needed to account for its role in health and well-being as well as its relevance for recovery and rehabilitation, we conducted a systematic review and meta-analysis of polysomnographic studies comparing stroke to control populations. Method Medline and PsycInfo databases were searched using stroke and words capturing polysomnographic parameters as search terms. This yielded 1692 abstracts for screening, with 15 meeting the criteria for systematic review and 9 for meta-analysis. Prisma best practice guidelines were followed for the systematic review; the Comprehensive Meta-Analysis software was used for random effects modelling. Results The meta-analysis revealed that patients with stroke have poorer sleep than controls. Patients had lower sleep efficiency (mean 75% vs 84%), shorter total-sleep-time (309.4 vs 340.3 min) and more wake-after-sleep-onset (97.2 vs 53.8 min). Patients also spend more time in stage 1 (13% vs 10%) and less time in stage 2 sleep (36% vs 45%) and slow-wave-sleep (10% vs 12%). No group differences were identified for REM sleep. The systematic review revealed a strong bias towards studies in the early recovery phase of stroke, with no study reporting specifically on patients in the chronic state. Moreover, participants in the control groups included community samples as well as other patients groups. Conclusions These results indicate poorer sleep in patients with stroke than controls. While strongly suggestive in nature, the evidence base is limited and methodologically diverse, and hands a clear mandate for further research. A particular need regards polysomnographic studies in chronic community-dwelling patients compared to age-matched individuals.

Upper Limb Immobilisation: A Neural Plasticity Model with Relevance to Poststroke Motor Rehabilitation.

Advances in our understanding of the neural plasticity that occurs after hemiparetic stroke have contributed to the formulation of theories of poststroke motor recovery. These theories, in turn, have underpinned contemporary motor rehabilitation strategies for treating motor deficits after stroke, such as upper limb hemiparesis. However, a relative drawback has been that, in general, these strategies are most compatible with the recovery profiles of relatively high-functioning stroke survivors and therefore do not easily translate into benefit to those individuals sustaining low-functioning upper limb hemiparesis, who otherwise have poorer residual function. For these individuals, alternative motor rehabilitation strategies are currently needed. In this paper, we will review upper limb immobilisation studies that have been conducted with healthy adult humans and animals. Then, we will discuss how the findings from these studies could inspire the creation of a neural plasticity model that is likely to be of particular relevance to the context of motor rehabilitation after stroke. For instance, as will be elaborated, such model could contribute to the development of alternative motor rehabilitation strategies for treating poststroke upper limb hemiparesis. The implications of the findings from those immobilisation studies for contemporary motor rehabilitation strategies will also be discussed and perspectives for future research in this arena will be provided as well.

Diversity of approaches in assessment of executive functions in stroke: Limited evidence?

Stroke is a leading cause of disability worldwide. Cognitive functions and, in particular, executive function, are commonly affected after stroke, leading to impairments in performance of daily activities, decrease in social participation and in quality of life. Appropriate assessment and understanding of executive dysfunction are important, firstly to develop better rehabilitation strategies for executive functions per se and secondly to consider executive function abilities on rehabilitation strategies in general. The purpose of this review was to identify the most widely used assessment tools of executive dysfunction for patients with stroke, and their psychometric properties. We systematically reviewed manuscripts published in English in databases from 1999 to 2015. We identified 35 publications. The most frequently used instruments were the Stroop, Digit Span and Trail making tests. Psychometric properties were described for the Executive Function Performance Test, Executive Clock Drawing Task, Chinese Frontal Assessment Battery and Virtual Action Planning — Supermarket, and two subtests of the Cambridge Cognitive Examination — Revised. There is a paucity of tools to reliably measure executive dysfunction after stroke, despite the fact that executive dysfunction is frequent. Identification of the best tools for executive dysfunction assessment is necessary to address important gaps in research and in clinical practice.

Application of Transcranial Direct Current Stimulation in Neurorehabilitation: The Modulatory Effect of Sleep.

The relationship between sleep disorders and neurological disorders is often reciprocal, such that sleep disorders are worsened by neurological symptoms and that neurological disorders are aggravated by poor sleep. Animal and human studies further suggest that sleep disruption not only worsens single neurological symptoms but may also lead to long-term negative outcomes. This suggests that sleep may play a fundamental role in neurorehabilitation and recovery. We further propose that sleep may not only alter the efficacy of behavioral treatments but also plasticity-enhancing adjunctive neurostimulation methods, such as transcranial direct current stimulation (tDCS). At present, sleep receives little attention in the fields of neurorehabilitation and neurostimulation. In this review, we draw together the strands of evidence from both fields of research to highlight the proposition that sleep is an important parameter to consider in the application of tDCS as a primary or adjunct rehabilitation intervention.

A case to be made: theoretical and empirical arguments for the need to consider fatigue in post-stroke motor rehabilitation

Motor rehabilitation after hemiparetic stroke is essential to soften physical disability (Furlan, 2014). Nevertheless, current interventions are mostly designed for well recovered individuals and often exclude stroke survivors with rather limited motor ability (Sterr and Conforto, 2012). Given that, and further advancing our research agenda in this arena (Sterr et al., 2002; Sterr and Freivogel, 2003, 2004; Sterr, 2004; Sterr et al., 2006; Sterr and Saunders, 2006), we recently tested the efficacy of a 2-week modified constraint-induced (CI) therapy program in chronic stroke individuals with very low-functioning upper limb hemiparesis (Sterr et al., 2014a). We tested the influence of both the intensity of daily motor training (90 vs. 180 minutes) and the restraint of the less affected upper limb (restraint vs. no restraint) on treatment outcomes. Sixty-five individuals were randomly assigned to four experimental conditions (90 minutes of training with or without restraint, and 180 minutes of training with or without restraint). They were assessed at baseline and after the intervention (2 weeks before, immediately before and after, 6, and 12 months after). Across the cohort, motor function improved significantly, and treatment benefits were largely sustained over the 12 months of follow-up. Analysis of the different treatment variants, however, revealed interesting yet unexpected findings, particularly with regards to the relationship between intensity (amount) of daily training and motor outcomes. As suggested by previous work (Sterr et al., 2002), longer sessions of daily training were expected to yield better outcomes than short sessions, a finding in line with the theory that massed practice is essential for neuroplasticity processes driving the functional improvements induced by CI therapy. However, this was not entirely the case. While we found some differences suggesting greater benefit of longer training sessions, the picture was not as clear as one might expect. This pointed to an interaction between training intensity and motor outcomes in low-functioning chronic stroke that appears to be different from that seen in less severe chronic hemiparesis, where the concept of ‘the more the better’ often holds true (Figure 1). We argued that this intensity-outcome relationship is moderated by variables that highly depend on the level of residual recovery. A key candidate for this moderation is fatigue. Fatigue is identified as rather common, yet obscure problem in stroke survivors (Wu et al., 2015). Post-stroke fatigue is multifactorial and seems to result from a complex interaction among biological, psychosocial, and behavioral factors (Wu et al., 2015). Here, we discuss the role of fatigue in motor rehabilitation of low-functioning chronic stroke using the framework recently suggested by Kluger et al. (2013). Although relatively different from, yet not antithetic to other fatigue models (e.g., Wu et al., 2015), we believe their framework provides conceptual and mechanistic support to our hypothesis. According to that framework, neurological, including post-stroke fatigue encompasses two domains: Perception of fatigue and fatigability. Perception of fatigue refers to a subjective sense of effort or exhaustion, whereas fatigability is related to an objective decline in performance. Although these two types of fatigue might be largely interrelated (e.g., an increased sense of effort would usually contribute to impair performance), they might also act independently and still significantly affect the individuals engagement with activities posing high motor and/or cognitive demands. This is because those two types of fatigue are likely to be caused by different, yet potentially interacting factors. For instance, perception of fatigue could be induced by homeostatic (e.g., metabolic stimuli, such as depletion of energy reserves in skeletal muscle and/or brain tissue) and/or psychological (e.g., decreased motivation) mechanisms, while fatigability could occur due to declines in skeletal muscle force production and/or deficits in task-related neural processing (Kluger et al., 2013). Based on that, we propose that low-functioning chronic stroke survivors are highly susceptible to get into a complex fatigued state, which renders motor training ineffective. This state is more likely to be reached by individuals undergoing longer training sessions. Essentially, we elaborate here on the possibility that a combination of general deconditioning and compromised neural processing might greatly increase both perception of fatigue and fatigability in those individuals, which substantially reduces their engagement with motor training and thereby decreases the likelihood for neuroplasticity processes driving behavioral improvements.

The Applicability of Standard Error of Measurement and Minimal Detectable Change to Motor Learning Research—A Behavioral Study

Motor learning studies face the challenge of differentiating between real changes in performance and random measurement error. While the traditional p-value-based analyses of difference (e.g., t-tests, ANOVAs) provide information on the statistical significance of a reported change in performance scores, they do not inform as to the likely cause or origin of that change, that is, the contribution of both real modifications in performance and random measurement error to the reported change. One way of differentiating between real change and random measurement error is through the utilization of the statistics of standard error of measurement (SEM) and minimal detectable change (MDC). SEM is estimated from the standard deviation of a sample of scores at baseline and a test–retest reliability index of the measurement instrument or test employed. MDC, in turn, is estimated from SEM and a degree of confidence, usually 95%. The MDC value might be regarded as the minimum amount of change that needs to be observed for it to be considered a real change, or a change to which the contribution of real modifications in performance is likely to be greater than that of random measurement error. A computer-based motor task was designed to illustrate the applicability of SEM and MDC to motor learning research. Two studies were conducted with healthy participants. Study 1 assessed the test–retest reliability of the task and Study 2 consisted in a typical motor learning study, where participants practiced the task for five consecutive days. In Study 2, the data were analyzed with a traditional p-value-based analysis of difference (ANOVA) and also with SEM and MDC. The findings showed good test–retest reliability for the task and that the p-value-based analysis alone identified statistically significant improvements in performance over time even when the observed changes could in fact have been smaller than the MDC and thereby caused mostly by random measurement error, as opposed to by learning. We suggest therefore that motor learning studies could complement their p-value-based analyses of difference with statistics such as SEM and MDC in order to inform as to the likely cause or origin of any reported changes in performance.

Potential for use of creatine supplementation following mild traumatic brain injury

There is significant overlap between the neuropathology of mild traumatic brain injury (mTBI) and the cellular role of creatine, as well as evidence of neural creatine alterations after mTBI. Creatine supplementation has not been researched in mTBI, but shows some potential as a neuroprotective when administered prior to or after TBI. Consistent with creatine’s cellular role, supplementation reduced neuronal damage, protected against the effects of cellular energy crisis and improved cognitive and somatic symptoms. A variety of factors influencing the efficacy of creatine supplementation are highlighted, as well as avenues for future research into the potential of supplementation as an intervention for mTBI. In particular, the slow neural uptake of creatine may mean that greater effects are achieved by pre-emptive supplementation in at-risk groups.