In recent years, new research has brought the field of electroencephalogram (EEG)-based brain–computer interfacing (BCI) out of its infancy and into a phase of relative maturity through many demonstrated prototypes such as brain-controlled wheelchairs, keyboards, and computer games. With this proof-of-concept phase in the past, the time is now ripe to focus on the development of practical BCI technologies that can be brought out of the lab and into real-world applications. In particular, we focus on the prospect of improving the lives of countless disabled individuals through a combination of BCI technology with existing assistive technologies (AT). In pursuit of more practical BCIs for use outside of the lab, in this paper, we identify four application areas where disabled individuals could greatly benefit from advancements in BCI technology, namely, “Communication and Control”, “Motor Substitution”, “Entertainment”, and “Motor Recovery”. We review the current state of the art and possible future developments, while discussing the main research issues in these four areas. In particular, we expect the most progress in the development of technologies such as hybrid BCI architectures, user–machine adaptation algorithms, the exploitation of users’ mental states for BCI reliability and confidence measures, the incorporation of principles in human–computer interaction (HCI) to improve BCI usability, and the development of novel BCI technology including better EEG devices.

Combining Brain-Computer Interfaces and Assistive Technologies: State-of-the-Art and Challenges.

Summary Background Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits. Methods In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5–10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163. Findings 118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7–38·4]) than in the placebo group (24·3 points [19·9–28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial seizure (one [ vs 0). Interpretation In patients with ischaemic stroke and moderate to severe motor deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after 3 months. Modulation of spontaneous brain plasticity by drugs is a promising pathway for treatment of patients with ischaemic stroke and moderate to severe motor deficit. Funding Public French National Programme for Clinical Research.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(10)70314-8.pdf

Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial

Longitudinal studies show that almost all stroke patients experience at least some predictable degree of functional recovery in the first six months post stroke. However, the non-linear pattern as a function of time is not well understood. Several mechanisms are presumed to be involved, such as recovery of penumbral tissues, neural plasticity, resolution of diaschisis and behavioural compensation strategies. Rehabilitation is believed to modulate this logistic pattern of recovery, probably by interacting with these underlying processes. However, prediction models that are adjusted for the effects of time after stroke onset suggest that outcome is largely defined within the first weeks post stroke, although functional improvement has been found to extend beyond six months post stroke. In addition, kinematic studies show that functional improvement is more than recovery from impairments alone, suggesting that patients are able to improve in terms of gait or dexterity deficits using behavioural compensation strategies. Therefore, understanding the impact of task-dependent cortical activation patterns in non-invasive methods requires not only information derived from longitudinal studies pertaining to functional outcomes, but also a better understanding of what is kinematically learned during the acquisition of new skills.

Understanding the pattern of functional recovery after stroke: facts and theories.

This document provides a review of the techniques and therapies used in gait rehabilitation after stroke. It also examines the possible benefits of including assistive robotic devices and brain-computer interfaces in this field, according to a top-down approach, in which rehabilitation is driven by neural plasticity. The methods reviewed comprise classical gait rehabilitation techniques (neurophysiological and motor learning approaches), functional electrical stimulation (FES), robotic devices, and brain-computer interfaces (BCI). From the analysis of these approaches, we can draw the following conclusions. Regarding classical rehabilitation techniques, there is insufficient evidence to state that a particular approach is more effective in promoting gait recovery than other. Combination of different rehabilitation strategies seems to be more effective than over-ground gait training alone. Robotic devices need further research to show their suitability for walking training and their effects on over-ground gait. The use of FES combined with different walking retraining strategies has shown to result in improvements in hemiplegic gait. Reports on non-invasive BCIs for stroke recovery are limited to the rehabilitation of upper limbs; however, some works suggest that there might be a common mechanism which influences upper and lower limb recovery simultaneously, independently of the limb chosen for the rehabilitation therapy. Functional near infrared spectroscopy (fNIRS) enables researchers to detect signals from specific regions of the cortex during performance of motor activities for the development of future BCIs. Future research would make possible to analyze the impact of rehabilitation on brain plasticity, in order to adapt treatment resources to meet the needs of each patient and to optimize the recovery process.

/pdf/rehabilitation-of-gait-after-stroke-a-review-towards-a-top-4ikeiisua7.pdf

Rehabilitation of gait after stroke: a review towards a top-down approach.

Spontaneous behavioral recovery is usually limited after stroke, making stroke a leading source of disability. A number of therapies in development aim to improve patient outcomes not by acutely salvaging threatened tissue, but instead by promoting repair and restoration of function in the subacute or chronic phase after stroke. Examples include small molecules, growth factors, cell-based therapies, electromagnetic stimulation, device-based strategies, and task-oriented and repetitive training-based interventions. Stage of development across therapies varies widely, from preclinical to late-phase clinical trials. The optimal methods to prescribe such therapies require further studies, for example, to best identify appropriate patients or to guide features of dosing. Likely, anatomic, functional, and behavioral measures of brain state, as well as measures of injury, will each be useful in this regard. Considerations for clinical trials of restorative therapies are provided, emphasizing both similarities and points of divergence with acute stroke clinical trial design.

Repairing the human brain after stroke. II. Restorative therapies.

Movement-related slow cortical potentials and event-related desynchronization of alpha (alpha-ERD) and beta (beta-ERD) activity after self-paced voluntary triangular finger movements were studied in 13 ischaemic supratentorial stroke patients and 10 age-matched control subjects during movement preparation and actual performance. The stroke patients suffered from central arm paresis (n = 8), somatosensory deficits (n = 3) or ideomotor apraxia (n = 2). The multimodal EEG analysis suggested impairment-specific changes in the movement-related electrical activity of the brain. The readiness potential of paretic subjects was centred more anteriorly and laterally; during movement, they showed increased beta-ERD at left lateral frontal recording sites. Patients with somatosensory deficits showed reduced alpha-ERD and beta-ERD during both movement preparation and actual performance. Patients with ideomotor apraxia showed more lateralized frontal movement-related slow cortical potentials during both movement preparation and performance, and reduced left parietal beta-ERD during movement preparation. We conclude that (i) disturbed motor efference is associated with an increased need for excitatory drive of pyramidal cells in motor and premotor areas or an attempt to drive movements through projections from these areas to brainstem motor systems during movement preparation; (ii) an undisturbed somatosensory afference might contribute to the release of relevant cortical areas from their 'idling' state when movements are prepared and performed; and (iii) apraxic patients have a relative lack of activity of the mesial frontal motor system and the left parietal cortex, which is believed to be part of a network subserving ideomotor praxis.

/pdf/multimodal-eeg-analysis-in-man-suggests-impairment-specific-17x1id1joq.pdf

Multimodal EEG analysis in man suggests impairment-specific changes in movement-related electric brain activity after stroke

Purpose. To assess the effects of d-amphetamine on motor facilitation and recovery in stroke patients with mild arm paresis receiving the Arm Ability training. Methods. Thirty-one stroke patients with mild arm paresis were randomly assigned to either (a.) receiving placebo or (b.) d-amphetamine twice a week 2 hours before Arm Ability training sessions for three weeks. Main outcome measure: time needed to perform TEMPA tasks, a measure of upper extremity performance reflecting everyday life tasks. Secondary measures: aimed movements, tapping, and a 10 m walkway as well as motor performance during training sessions. Results. The interim efficacy analysis of 26 stroke patients who completed the study intervention showed overall arm motor recovery both from pre to post test after 3 weeks of training and from pre test to follow-up 1 year later. No superior effect of d-amphetamine over placebo could be substantiated for either motor facilitation during training or motor recovery (post training or long-term). D-amphetamine exerted mild effects on blood pressure. Serious adverse events were not observed. Conclusions. d-Amphetamine failed to facilitate motor performance during training sessions, to promote skill acquisition with training tasks, and most importantly to enhance motor recovery among patients with mild arm paresis after stroke.

Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: interim analysis and termination of a double blind, randomised, placebo-controlled trial.

Purpose: Receiving the Arm Ability Training for three weeks improves motor function among stroke patients with mild arm paresis. There is, however, a considerable variability in recovery among patients receiving the Arm Ability Training. The study investigated whether intersubject differences in movement-related electric brain activity explain the variability in motor recovery. Methods: In a sample of 9 patients receiving the Arm Ability Training both motor performance using a standardised arm function test (TEMPA) and movement-related electric brain activity, i.e. slow cortical potentials (DC) as well as event-related desynchronisation of alpha (alpha-ERD) and beta activity (beta-ERD), were assessed before the Arm Ability Training was started. Stepwise multiple regression was used to establish the best predictive model for motor improvement scores (TEMPA difference from pre to post test three weeks later). Results: Stepwise multiple regression indicated that electric brain activity during movement preparation explained the variance of motor improvement scores completely. Further, electric brain activity during movement as well as baseline motor performance accounted each for 50% of the variance of motor improvement scores. Conclusions: Activation of sensorimotor areas during movement preparation and deactivation of other cortical areas during movement execution seem to be factors that predict a favourable outcome after training.

Brain activation pattern as assessed with multi-modal EEG analysis predict motor recovery among stroke patients with mild arm paresis who receive the Arm Ability Training.

I.-H. Kim

Papers

Multimodal EEG analysis in man suggests impairment-specific changes in movement-related electric brain activity after stroke

Amphetamine fails to facilitate motor performance and to enhance motor recovery among stroke patients with mild arm paresis: interim analysis and termination of a double blind, randomised, placebo-controlled trial.

Brain activation pattern as assessed with multi-modal EEG analysis predict motor recovery among stroke patients with mild arm paresis who receive the Arm Ability Training.