Sleep and motor learning in stroke (SMiLES): a longitudinal study investigating sleep-dependent consolidation of motor sequence learning in the context of recovery after stroke.

INTRODUCTION: There is growing evidence that sleep is disrupted after stroke, with worse sleep relating to poorer motor outcomes. It is also widely acknowledged that consolidation of motor learning, a critical component of poststroke recovery, is sleep-dependent. However, whether the relationship between disrupted sleep and poor outcomes after stroke is related to direct interference of sleep-dependent motor consolidation processes, is currently unknown. Therefore, the aim of the present study is to understand whether measures of motor consolidation mediate the relationship between sleep and clinical motor outcomes post stroke. METHODS AND ANALYSIS: We will conduct a longitudinal observational study of up to 150 participants diagnosed with stroke affecting the upper limb. Participants will be recruited and assessed within 7 days of their stroke and followed up at approximately 1 and 6 months. The primary objective of the study is to determine whether sleep in the subacute phase of recovery explains the variability in upper limb motor outcomes after stroke (over and above predicted recovery potential from the Predict Recovery Potential algorithm) and whether this relationship is dependent on consolidation of motor learning. We will also test whether motor consolidation mediates the relationship between sleep and whole-body clinical motor outcomes, whether motor consolidation is associated with specific electrophysiological sleep signals and sleep alterations during subacute recovery. ETHICS AND DISSEMINATION: This trial has received both Health Research Authority, Health and Care Research Wales and National Research Ethics Service approval (IRAS: 304135; REC: 22/LO/0353). The results of this trial will help to enhance our understanding of the role of sleep in recovery of motor function after stroke and will be disseminated via presentations at scientific conferences, peer-reviewed publication, public engagement events, stakeholder organisations and other forms of media where appropriate. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT05746260, registered on 27 February 2023.

Improving sleep after stroke: A randomised controlled trial of digital cognitive behavioural therapy for insomnia.

Stroke is frequently accompanied by long-term sleep disruption. We therefore aimed to assess the efficacy of digital cognitive behavioural therapy for insomnia to improve sleep after stroke. A parallel group randomised controlled trial was conducted remotely in participant's homes/online. Randomisation was online with minimisation of between-group differences in age and baseline Sleep Condition Indicator-8 score. In total, 86 community-dwelling stroke survivors consented, of whom 84 completed baseline assessments (39 female, mean 5.5 years post-stroke, mean 59 years old), and were randomised to digital cognitive behavioural therapy or control (sleep hygiene information). Follow-up was at post-intervention (mean 75 days after baseline) and 8 weeks later. The primary outcome was self-reported insomnia symptoms, as per the Sleep Condition Indicator-8 (range 0-32, lower numbers indicate more severe insomnia, reliable change 7 points) at post-intervention. There were significant improvements in Sleep Condition Indicator-8 for digital cognitive behavioural therapy compared with control (intention-to-treat, digital cognitive behavioural therapy n = 48, control n = 36, 5 imputed datasets, effect of group p ≤ 0.02, η p 2 = 0.07-0.12 [medium size effect], pooled mean difference = -3.35). Additionally, secondary outcomes showed shorter self-reported sleep-onset latencies and better mood for the digital cognitive behavioural therapy group, but no significant differences for self-efficacy, quality of life or actigraphy-derived sleep parameters. Cost-effectiveness analysis found that digital cognitive behavioural therapy dominates over control (non-significant cost savings and higher quality-adjusted life years). No related serious adverse events were reported to the researchers. Overall, digital cognitive behavioural therapy for insomnia effectively improves sleep after stroke. Future research is needed to assess earlier stages post-stroke, with a longer follow-up period to determine whether it should be included as part of routine post-stroke care. Clinicaltrials.gov NCT04272892.

A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: Consensus-based core recommendations from the third stroke recovery and rehabilitation roundtable.

BACKGROUND AND AIMS: The purpose of this Third Stroke Recovery and Rehabilitation Roundtable (SRRR3) was to develop consensus recommendations to address outstanding barriers for the translation of preclinical and clinical research using the non-invasive brain stimulation (NIBS) techniques Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) and provide a roadmap for the integration of these techniques into clinical practice. METHODS: International NIBS and stroke recovery experts (N = 18) contributed to the consensus process. Using a nominal group technique, recommendations were reached via a five-stage process, involving a thematic survey, two priority ranking surveys, a literature review and an in-person meeting. RESULTS AND CONCLUSIONS: Results of our consensus process yielded five key evidence-based and feasibility barriers for the translation of preclinical and clinical NIBS research, which were formulated into five core consensus recommendations. Recommendations highlight an urgent need for (1) increased understanding of NIBS mechanisms, (2) improved methodological rigor in both preclinical and clinical NIBS studies, (3) standardization of outcome measures, (4) increased clinical relevance in preclinical animal models, and (5) greater optimization and individualization of NIBS protocols. To facilitate the implementation of these recommendations, the expert panel developed a new SRRR3 Unified NIBS Research Checklist. These recommendations represent a translational pathway for the use of NIBS in stroke rehabilitation research and practice.

A translational roadmap for transcranial magnetic and direct current stimulation in stroke rehabilitation: Consensus-based core recommendations from the third stroke recovery and rehabilitation roundtable.

BACKGROUND AND AIMS: The purpose of this Third Stroke Recovery and Rehabilitation Roundtable (SRRR3) was to develop consensus recommendations to address outstanding barriers for the translation of preclinical and clinical research using the non-invasive brain stimulation (NIBS) techniques Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current Stimulation (tDCS) and provide a roadmap for the integration of these techniques into clinical practice. METHODS: International NIBS and stroke recovery experts (N = 18) contributed to the consensus process. Using a nominal group technique, recommendations were reached via a five-stage process, involving a thematic survey, two priority ranking surveys, a literature review and an in-person meeting. RESULTS AND CONCLUSIONS: Results of our consensus process yielded five key evidence-based and feasibility barriers for the translation of preclinical and clinical NIBS research, which were formulated into five core consensus recommendations. Recommendations highlight an urgent need for (1) increased understanding of NIBS mechanisms, (2) improved methodological rigor in both preclinical and clinical NIBS studies, (3) standardization of outcome measures, (4) increased clinical relevance in preclinical animal models, and (5) greater optimization and individualization of NIBS protocols. To facilitate the implementation of these recommendations, the expert panel developed a new SRRR3 Unified NIBS Research Checklist. These recommendations represent a translational pathway for the use of NIBS in stroke rehabilitation research and practice.

The effect of pulse shape in theta-burst stimulation: Monophasic vs biphasic TMS.

BACKGROUND: Intermittent theta-burst stimulation (i) (TBS) is a transcranial magnetic stimulation (TMS) plasticity protocol. Conventionally, TBS is applied using biphasic pulses due to hardware limitations. However, monophasic pulses are hypothesised to recruit cortical neurons more selectively than biphasic pulses, predicting stronger plasticity effects. Monophasic and biphasic TBS can be generated using a custom-made pulse-width modulation-based TMS device (pTMS). OBJECTIVE: Using pTMS, we tested the hypothesis that monophasic iTBS would induce a stronger plasticity effect than biphasic, measured as induced increases in motor corticospinal excitability. METHODS: In a repeated-measures design, thirty healthy volunteers participated in three separate sessions, where monophasic and biphasic iTBS was applied to the primary motor cortex (M1 condition) or the vertex (control condition). Plasticity was quantified as increases in motor corticospinal excitability after versus before iTBS, by comparing peak-to-peak amplitudes of motor evoked potentials (MEP) measured at baseline and over 60 min after iTBS. RESULTS: Both monophasic and biphasic M1 iTBS led to significant increases in MEP amplitude. As predicted, linear mixed effects (LME) models showed that the iTBS condition had a significant effect on the MEP amplitude (χ2 (1) = 27.615, p < 0.001) with monophasic iTBS leading to significantly stronger plasticity than biphasic iTBS (t (693) = 2.311, p = 0.021). Control vertex iTBS had no effect. CONCLUSIONS: In this study, monophasic iTBS induced a stronger motor corticospinal excitability increase than biphasic within participants. This greater physiological effect suggests that monophasic iTBS may also have potential for greater functional impact, of interest for future fundamental and clinical applications of TBS.

Improving sleep and learning in rehabilitation after stroke, part 2 (INSPIRES2): study protocol for a home-based randomised control trial of digital cognitive behavioural therapy (dCBT) for insomnia.

INTRODUCTION: Consolidation of motor skill learning, a key component of rehabilitation post-stroke, is known to be sleep dependent. However, disrupted sleep is highly prevalent after stroke and is often associated with poor motor recovery and quality of life. Previous research has shown that digital cognitive behavioural therapy (dCBT) for insomnia can be effective at improving sleep quality after stroke. Therefore, the aim of this trial is to evaluate the potential for sleep improvement using a dCBT programme, to improve rehabilitation outcomes after stroke. METHODS AND ANALYSIS: We will conduct a parallel-arm randomised controlled trial of dCBT (Sleepio) versus treatment as usual among individuals following stroke affecting the upper limb. Up to 100 participants will be randomly allocated (2:1) into either the intervention (6-8 week dCBT) or control (continued treatment as usual) group. The primary outcome of the study will be change in insomnia symptoms pre to post intervention compared with treatment as usual. Secondary outcomes include improvement in overnight motor memory consolidation and sleep measures between intervention groups, correlations between changes in sleep behaviour and overnight motor memory consolidation in the dCBT group and changes in symptoms of depression and fatigue between the dCBT and control groups. Analysis of covariance models and correlations will be used to analyse data from the primary and secondary outcomes. ETHICS AND DISSEMINATION: The study has received approval from the National Research Ethics Service (22/EM/0080), Health Research Authority (HRA) and Health and Care Research Wales (HCRW), IRAS ID: 306 291. The results of this trial will be disseminated via presentations at scientific conferences, peer-reviewed publication, public engagement events, stakeholder organisations and other forms of media where appropriate. TRIAL REGISTRATION NUMBER: NCT05511285.

Individual differences in slow wave sleep architecture relate to variation in white matter microstructure across adulthood.

Sleep plays a key role in supporting brain function and resilience to brain decline. It is well known that sleep changes substantially with aging and that aging is associated with deterioration of brain structure. In this study, we sought to characterize the relationship between slow wave slope (SWslope)-a key marker of sleep architecture and an indirect proxy of sleep quality-and microstructure of white matter pathways in healthy adults with no sleep complaints. Participants were 12 young (24-27 years) and 12 older (50-79 years) adults. Sleep was assessed with nocturnal electroencephalography (EEG) and the Pittsburgh Sleep Quality Index (PSQI). White matter integrity was assessed using tract-based spatial statistics (TBSS) on tensor-based metrics such as Fractional Anisotropy (FA) and Mean Diffusivity (MD). Global PSQI score did not differ between younger (n = 11) and older (n = 11) adults (U = 50, p = 0.505), but EEG revealed that younger adults had a steeper SWslope at both frontal electrode sites (F3: U = 2, p < 0.001, F4: U = 4, p < 0.001, n = 12 younger, 10 older). There were widespread correlations between various diffusion tensor-based metrics of white matter integrity and sleep SWslope, over and above effects of age (n = 11 younger, 9 older). This was particularly evident for the corpus callosum, corona radiata, superior longitudinal fasciculus, internal and external capsule. This indicates that reduced sleep slow waves may be associated with widespread white matter deterioration. Future studies should investigate whether interventions targeted at improving sleep architecture also impact on decline in white matter microstructure in older adults.

Self-modulation of motor cortex activity after stroke: a randomized controlled trial.

Real-time functional MRI neurofeedback allows individuals to self-modulate their ongoing brain activity. This may be a useful tool in clinical disorders that are associated with altered brain activity patterns. Motor impairment after stroke has previously been associated with decreased laterality of motor cortex activity. Here we examined whether chronic stroke survivors were able to use real-time fMRI neurofeedback to increase laterality of motor cortex activity and assessed effects on motor performance and on brain structure and function. We carried out a randomized, double-blind, sham-controlled trial (ClinicalTrials.gov: NCT03775915) in which 24 chronic stroke survivors with mild to moderate upper limb impairment experienced three training days of either Real (n = 12) or Sham (n = 12) neurofeedback. Assessments of brain structure, brain function and measures of upper-limb function were carried out before and 1 week after neurofeedback training. Additionally, measures of upper-limb function were repeated 1 month after neurofeedback training. Primary outcome measures were (i) changes in lateralization of motor cortex activity during movements of the stroke-affected hand throughout neurofeedback training days; and (ii) changes in motor performance of the affected limb on the Jebsen Taylor Test (JTT). Stroke survivors were able to use Real neurofeedback to increase laterality of motor cortex activity within (P = 0.019), but not across, training days. There was no group effect on the primary behavioural outcome measure, which was average JTT performance across all subtasks (P = 0.116). Secondary analysis found improvements in the performance of the gross motor subtasks of the JTT in the Real neurofeedback group compared to Sham (P = 0.010). However, there were no improvements on the Action Research Arm Test or the Upper Extremity Fugl-Meyer score (both P > 0.5). Additionally, decreased white-matter asymmetry of the corticospinal tracts was detected 1 week after neurofeedback training (P = 0.008), indicating that the tracts become more similar with Real neurofeedback. Changes in the affected corticospinal tract were positively correlated with participants neurofeedback performance (P = 0.002). Therefore, here we demonstrate that chronic stroke survivors are able to use functional MRI neurofeedback to self-modulate motor cortex activity in comparison to a Sham control, and that training is associated with improvements in gross hand motor performance and with white matter structural changes.

A qualitative examination of the usability of a digital cognitive behavioral therapy for insomnia program after stroke.

OBJECTIVE: Sleep is commonly impaired after stroke. Cognitive Behavioral Therapy for Insomnia (CBT-I) is the first-line recommended treatment for sleep difficulty. "Sleepio" is a digital CBT-I program, allowing delivery of this treatment at scale. However, Sleepio has not yet been tested specifically in people with stroke. Before doing so, we wanted to explore the experience of people with stroke using the program, and potential barriers to completion. METHOD: Community dwelling survivors of stroke (n = 11, 41-78 years of age, 6 male) were given access to Sleepio. Participants discussed their experiences with the program during a semi-structured interview, which was analyzed using thematic analysis. RESULTS: We found four common themes: (1) positive and negative experiences impacted engagement with the program, (2) motivation to follow the program was proportional to perceived severity of sleep problem, (3) impractical advice for people with stroke, (4) difficulty operating the program. CONCLUSION: Sleepio can be used by some people at the chronic stage of stroke. However, some barriers to completion were highlighted, and not all suggestions were deemed practical for everyone. We therefore suggest possible adaptations which may make the program more easily usable and engaging for survivors of stroke with varying impairments.

Self-Reported and Objective Sleep Measures in Stroke Survivors With Incomplete Motor Recovery at the Chronic Stage.

Background. Stroke survivors commonly complain of difficulty sleeping. Poor sleep is associated with reduced quality of life and more understanding of long-term consequences of stroke on sleep is needed. Objective. The primary aims were to (1) compare sleep measures between chronic stroke survivors and healthy controls and (2) test for a relationship between motor impairment, time since stroke and sleep. Secondary aims were to explore mood and inactivity as potential correlates of sleep and test the correlation between self-reported and objective sleep measures. Methods. Cross-sectional sleep measures were obtained for 69 chronic stroke survivors (mean 65 months post-stroke, 63 years old, 24 female) and 63 healthy controls (mean 61 years old, 27 female). Self-reported sleep was assessed with the sleep condition indicator (SCI) and sleep diary ratings, objective sleep with 7-nights actigraphy and mood with the Hospital Anxiety and Depression Scale. Upper extremity motor impairment was assessed with the Fugl-Meyer assessment. Results. Stroke survivors had significantly poorer SCI score (P < .001) and higher wake after sleep onset (P = .005) than controls. Neither motor impairment, nor time since stroke, explained significant variance in sleep measures for the stroke group. For all participants together, greater depression was associated with poorer SCI score (R2adj = .197, P < .001) and higher age with more fragmented sleep (R2adj = .108, P < .001). There were weak correlations between nightly sleep ratings and actigraphy sleep measures (rs = .15-.24). Conclusions. Sleep disturbance is present long-term after stroke. Depressive symptoms may present a modifiable factor which should be investigated alongside techniques to improve sleep in this population.

Dual-task walking and automaticity after Stroke: Insights from a secondary analysis and imaging sub-study of a randomised controlled trial.

OBJECTIVE: To test the extent to which initial walking speed influences dual-task performance after walking intervention, hypothesising that slow walking speed affects automatic gait control, limiting executive resource availability. DESIGN: A secondary analysis of a trial of dual-task (DT) and single-task (ST) walking interventions comparing those with good (walking speed ⩾0.8 m s-1, n = 21) and limited (walking speed <0.79 m s-1, n = 24) capacity at baseline. SETTING: Community. SUBJECTS: Adults six-months post stroke with walking impairment. INTERVENTIONS: Twenty sessions of 30 minutes treadmill walking over 10 weeks with (DT) or without (ST) cognitive distraction. Good and limited groups were formed regardless of intervention received. MAIN MEASURES: A two-minute walk with (DT) and without (ST) a cognitive distraction assessed walking. fNIRS measured prefrontal cortex activation during treadmill walking with (DT) and without (ST) Stroop and planning tasks and an fMRI sub-study used ankle-dorsiflexion to simulate walking. RESULTS: ST walking improved in both groups (∆baseline: Good = 8.9 ± 13.4 m, limited = 5.3±8.9 m, Group × time = P < 0.151) but only the good walkers improved DT walking (∆baseline: Good = 10.4 ± 13.9 m, limited = 1.3 ± 7.7 m, Group × time = P < 0.025). fNIRS indicated increased ispilesional prefrontal cortex activation during DT walking following intervention (P = 0.021). fMRI revealed greater DT cost activation for limited walkers, and increased resting state connectivity of contralesional M1 with cortical areas associated with conscious gait control at baseline. After the intervention, resting state connectivity between ipsilesional M1 and bilateral superior parietal lobe, involved in integrating sensory and motor signals, increased in the good walkers compared with limited walkers. CONCLUSION: In individual who walk slowly it may be difficult to improve dual-task walking ability.Registration: ISRCTN50586966.

Sleep Disruption After Brain Injury Is Associated With Worse Motor Outcomes and Slower Functional Recovery.

Background. Sleep is important for consolidation of motor learning, but brain injury may affect sleep continuity and therefore rehabilitation outcomes. Objective. This study aims to assess the relationship between sleep quality and motor recovery in brain injury patients receiving inpatient rehabilitation. Methods. Fifty-nine patients with brain injury were recruited from 2 specialist inpatient rehabilitation units. Sleep quality was assessed (up to 3 times) objectively using actigraphy (7 nights) and subjectively using the Sleep Condition Indicator. Motor outcome assessments included Action Research Arm test (upper limb function), Fugl-Meyer Assessment (motor impairment), and the Rivermead Mobility Index. The Functional Independence Measure (FIM) was assessed at admission and discharge by the clinical team. Fifty-five age- and gender-matched healthy controls completed one assessment. Results. Inpatients demonstrated lower self-reported sleep quality (P < .001) and more fragmented sleep (P < .001) than controls. For inpatients, sleep fragmentation explained significant additional variance in motor outcomes, over and above that explained by admission FIM score (P < .017), such that more disrupted sleep was associated with poorer motor outcomes. Using stepwise linear regression, sleep fragmentation was the only variable found to explain variance in rate of change in FIM (R2adj = 0.12, P = .027), whereby more disrupted sleep was associated with slower recovery. Conclusions. Inpatients with brain injury demonstrate impaired sleep quality, and this is associated with poorer motor outcomes and slower functional recovery. Further investigation is needed to determine how sleep quality can be improved and whether this affects outcome.

Transcranial direct current stimulation for promoting motor function in cerebral palsy: a review.

Transcranial direct current stimulation (tDCS) has the potential to improve motor function in a range of neurological conditions, including Cerebral Palsy (CP). Although there have been many studies assessing tDCS in adult stroke, the literature regarding the efficacy of tDCS in CP is more limited. This review therefore focuses on the neurophysiological and clinical findings in children and adolescents with CP. Initial studies applying anodal tDCS to promote lower limb function are promising, with improvements in gait, mobility and balance reported. However, the results of upper limb studies are mixed and more research is needed. Studies investigating neurophysiological changes or predictors of response are also lacking. Large-scale longitudinal studies are needed for the lower limb to ascertain whether the initial pilot results translate into clinically meaningful improvements. Future studies of the upper limb should focus on determining the optimal stimulation parameters and consider tailoring stimulation to the individual based on the (re)organisation of their motor system.

Explicit motor sequence learning with the paretic arm after stroke.

PURPOSE: Motor sequence learning is important for stroke recovery, but experimental tasks require dexterous movements, which are impossible for people with upper limb impairment. This makes it difficult to draw conclusions about the impact of stroke on learning motor sequences. We aimed to test a paradigm requiring gross arm movements to determine whether stroke survivors with upper limb impairment were capable of learning a movement sequence as effectively as age-matched controls. MATERIALS AND METHODS: In this case-control study, 12 stroke survivors (10-138 months post-stroke, mean age 64 years) attempted the task once using their affected arm. Ten healthy controls (mean 66 years) used their non-dominant arm. A sequence of 10 movements was repeated 25 times. The variables were: time from target illumination until the cursor left the central square (onset time; OT), accuracy (path length), and movement speed. RESULTS: OT reduced with training (p < 0.05) for both groups, with no change in movement speed or accuracy (p > 0.1). We quantified learning as the OT difference between the end of training and a random sequence; this was smaller for stroke survivors than controls (p = 0.015). CONCLUSIONS: Stroke survivors can learn a movement sequence with their paretic arm, but demonstrate impairments in sequence specific learning. Implications for Rehabilitation Motor sequence learning is important for recovery of movement after stroke. Stroke survivors were found to be capable of learning a movement sequence with their paretic arm, supporting the concept of repetitive task training for recovery of movement. Stroke survivors showed impaired sequence specific learning in comparison with age-matched controls, indicating that they may need more repetitions of a sequence in order to re-learn movements. Further research is required into the effect of lesion location, time since stroke, hand dominance and gender on learning of motor sequences after stroke.

The effect of transcranial direct current stimulation on motor sequence learning and upper limb function after stroke.

OBJECTIVE: To assess the impact of electrode arrangement on the efficacy of tDCS in stroke survivors and determine whether changes in transcallosal inhibition (TCI) underlie improvements. METHODS: 24 stroke survivors (3-124months post-stroke) with upper limb impairment participated. They received blinded tDCS during a motor sequence learning task, requiring the paretic arm to direct a cursor to illuminating targets on a monitor. Four tDCS conditions were studied (crossover); anodal to ipsilesional M1, cathodal to contralesional M1, bihemispheric, sham. The Jebsen Taylor hand function test (JTT) was assessed pre- and post-stimulation and TCI assessed as the ipsilateral silent period (iSP) duration using transcranial magnetic stimulation. RESULTS: The time to react to target illumination reduced with learning of the movement sequence, irrespective of tDCS condition (p>0.1). JTT performance improved after unilateral tDCS (anodal or cathodal) compared with sham (p<0.05), but not after bihemispheric (p>0.1). There was no effect of tDCS on change in iSP duration (p>0.1). CONCLUSIONS: Unilateral tDCS is effective for improving JTT performance, but not motor sequence learning. SIGNIFICANCE: This has implications for the design of future clinical trials.

Non-invasive brain stimulation for the lower limb after stroke: what do we know so far and what should we be doing next?

BACKGROUND: Non-invasive brain stimulation (NIBS) is promising as an adjuvant to rehabilitation of motor function after stroke. Despite numerous studies and reviews for the upper limb, NIBS targeting the lower limb and gait recovery after stroke is a newly emerging field of research. PURPOSE: To summarize findings from studies using NIBS to target the lower limb in stroke survivors. METHODS: This narrative review describes studies of repetitive transcranial magnetic stimulation, paired associative stimulation and transcranial direct current stimulation with survivors of stroke. RESULTS: NIBS appears capable of inducing changes in cortical excitability and lower limb function, but stimulation parameters and study designs vary considerably making it difficult to determine effectiveness. CONCLUSIONS: Future research should systematically assess differences in response with different stimulation parameters, test measures for determining who would be most likely to benefit and assess effectiveness with large samples before NIBS can be considered for use in clinical practice. Implications for Rehabilitation Stroke is a leading cause of disability, often resulting in dependency in activities of daily living and reduced quality of life. Non-invasive brain stimulation has received considerable interest as a potential adjuvant to rehabilitation after stroke and this review summarizes studies targeting the lower limb and gait recovery. Non-invasive brain stimulation can be used to modulate excitability of lower limb muscle representations and can lead to improvements in motor performance in stroke survivors. Non-invasive brain stimulation for gait recovery needs further investigation before translation to clinical practice is possible.

Fluoxetine Does Not Enhance Visual Perceptual Learning and Triazolam Specifically Impairs Learning Transfer.

The selective serotonin reuptake inhibitor fluoxetine significantly enhances adult visual cortex plasticity within the rat. This effect is related to decreased gamma-aminobutyric acid (GABA) mediated inhibition and identifies fluoxetine as a potential agent for enhancing plasticity in the adult human brain. We tested the hypothesis that fluoxetine would enhance visual perceptual learning of a motion direction discrimination (MDD) task in humans. We also investigated (1) the effect of fluoxetine on visual and motor cortex excitability and (2) the impact of increased GABA mediated inhibition following a single dose of triazolam on post-training MDD task performance. Within a double blind, placebo controlled design, 20 healthy adult participants completed a 19-day course of fluoxetine (n = 10, 20 mg per day) or placebo (n = 10). Participants were trained on the MDD task over the final 5 days of fluoxetine administration. Accuracy for the trained MDD stimulus and an untrained MDD stimulus configuration was assessed before and after training, after triazolam and 1 week after triazolam. Motor and visual cortex excitability were measured using transcranial magnetic stimulation. Fluoxetine did not enhance the magnitude or rate of perceptual learning and full transfer of learning to the untrained stimulus was observed for both groups. After training was complete, trazolam had no effect on trained task performance but significantly impaired untrained task performance. No consistent effects of fluoxetine on cortical excitability were observed. The results do not support the hypothesis that fluoxetine can enhance learning in humans. However, the specific effect of triazolam on MDD task performance for the untrained stimulus suggests that learning and learning transfer rely on dissociable neural mechanisms.

Reliability of Transcallosal Inhibition in Healthy Adults.

Transcallosal inhibition (TCI), assessed using transcranial magnetic stimulation, can provide insight into the neurophysiology of aging and of neurological disorders such as stroke. However, the reliability of TCI using the ipsilateral silent period (iSP) has not been formally assessed, despite its use in longitudinal studies. This study aimed to determine the reliability of iSP onset latency, duration and depth in healthy young and older adults. A sample of 18 younger (mean age 27.7 years, range: 19-42) and 13 older healthy adults (mean age 68.1 years, range: 58-79) attended four sessions whereby the iSP was measured from the first dorsal interosseous (FDI) muscle of each hand. 20 single pulse stimuli were delivered to each primary motor cortex at 80% maximum stimulator output while the participant maintained an isometric contraction of the ipsilateral FDI. The average onset latency, duration of the iSP, and depth of inhibition relative to baseline electromyography activity was calculated for each hand in each session. Intraclass correlation coefficients (ICCs) were calculated for all four sessions, or the first two sessions only. For iSP onset latency the reliability ranged from poor to good. For iSP duration there was moderate to good reliability (ICC > 0.6). Depth of inhibition demonstrated variation in reproducibility depending on which hand was assessed and whether two or four sessions were compared. Bland and Altman analyses showed wide limits of agreement between the first two sessions, particularly for iSP depth. However, there was no systematic pattern to the variability. These results indicate that although iSP duration is reliable in healthy adults, changes in longitudinal studies should be interpreted with caution, particularly for iSP depth. Future studies are needed to determine reliability in clinical populations.

The effect of combined somatosensory stimulation and task-specific training on upper limb function in chronic stroke: a double-blind randomized controlled trial.

BACKGROUND: Somatosensory stimulation (SS) is a potential adjuvant to stroke rehabilitation, but the effect on function needs further investigation. OBJECTIVE: To explore the effect of combining SS with task-specific training (TST) on upper limb function and arm use in chronic stroke survivors and determine underlying mechanisms. METHODS: In this double-blinded randomized controlled trial (ISRCTN 05542931), 33 patients (mean 37.7 months poststroke) were block randomized to 2 groups: active or sham SS. They received 12 sessions of 2 hours of SS (active or sham) to all 3 upper limb nerves immediately before 30 minutes of TST. The primary outcome was the Action Research Arm Test (ARAT) score. Secondary outcomes were time to perform the ARAT, Fugl-Meyer Assessment score (FM), Motor Activity Log (MAL), and Goal Attainment Scale (GAS). Underlying mechanisms were explored using transcranial magnetic stimulation stimulus-response curves and intracortical inhibition. Outcomes were assessed at baseline, immediately following the intervention (mean 2 days), and 3 and 6 months (mean 96 and 190 days) after the intervention. RESULTS: The active group (n = 16) demonstrated greater improvement in ARAT score and time immediately postintervention (between-group difference; P < .05), but not at 3- or 6-month follow-ups (P > .2). Within-group improvements were seen for both groups for ARAT and GAS, but for the active group only for FM and MAL (P < .05). Corticospinal excitability did not change. CONCLUSIONS: Long-lasting improvements in upper limb function were observed following TST. Additional benefit of SS was seen immediately post treatment, but did not persist and the underlying mechanisms remain unclear.

Self-perceived utilization of the paretic arm in chronic stroke requires high upper limb functional ability.

OBJECTIVE: To explore potential predictors of self-reported paretic arm use at baseline and after task-specific training (TST) in survivors of stroke. DESIGN: Data were obtained from a randomized controlled trial of somatosensory stimulation and upper limb TST in chronic stroke. SETTING: University laboratory. PARTICIPANTS: Chronic (≥3mo) survivors of stroke (N=33; mean age, 62y; mean stroke duration, 38mo). INTERVENTIONS: Participants received 12 sessions of TST preceded by either active (n=16) or sham (n=17) somatosensory stimulation to all 3 peripheral nerves. MAIN OUTCOME MEASURES: Demographic and clinical characteristics were entered stepwise into multiple linear regression analyses to determine the factors that best predict baseline Motor Activity Log (MAL) amount of use rating and change 3 months after TST. RESULTS: The Action Research Arm Test (ARAT) score predicted the amount of use at baseline (R(2)=.47, P<.001); in using this model, an ARAT score of 54 (maximum of 57) is required to score 2.5 on the MAL (use described as between rarely and sometimes). After TST the change in the ARAT score predicted the change in the amount of use (R(2)=.31, P=.001). The predictive power of the model for change at 3 months increased if the Fugl-Meyer Assessment wrist component score was added (R(2)=.41, P=.001). CONCLUSIONS: Utilization of the paretic upper limb in activities of daily living requires high functional ability. The increase in self-reported arm use after TST is dependent on the change in functional ability. These results provide further guidance for rehabilitation decisions.