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 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.

Performance on the balloon analogue risk task and anticipatory response inhibition task is associated with severity of impulse control behaviours in people with Parkinson's disease.

Dopamine agonist medication is one of the largest risk factors for development of problematic impulse control behaviours (ICBs) in people with Parkinson's disease. The present study investigated the potential of dopamine gene profiling and individual performance on impulse control tasks to explain ICB severity. Clinical, genetic and task performance data were entered into a mixed-effects linear regression model for people with Parkinson's disease taking (n = 50) or not taking (n = 25) dopamine agonist medication. Severity of ICBs was captured via the Questionnaire for Impulsive-compulsive disorders in Parkinson's disease Rating Scale. A cumulative dopamine genetic risk score (DGRS) was calculated for each participant from variance in five dopamine-regulating genes. Objective measures of impulsive action and impulsive choice were measured on the Anticipatory Response Inhibition Task and Balloon Analogue Risk Task, respectively. For participants on dopamine agonist medication, task performance reflecting greater impulsive choice (p = 0.014), and to a trend level greater impulsive action (p = 0.056), as well as a longer history of DA medication (p < 0.001) all predicted increased ICB severity. DGRS however, did not predict ICB severity (p = 0.708). No variables could explain ICB severity in the non-agonist group. Our task-derived measures of impulse control have the potential to predict ICB severity in people with Parkinson's and warrant further investigation to determine whether they can be used to monitor ICB changes over time. The DGRS appears better suited to predicting the incidence, rather than severity, of ICBs on agonist medication.

Short duration event related cerebellar TDCS enhances visuomotor adaptation.

BACKGROUND: Transcranial direct current stimulation (TDCS) is typically applied before or during a task, for periods ranging from 5 to 30 min. HYPOTHESIS: We hypothesise that briefer stimulation epochs synchronous with individual task actions may be more effective. METHODS: In two separate experiments, we applied brief bursts of event-related anodal stimulation (erTDCS) to the cerebellum during a visuomotor adaptation task. RESULTS: The first study demonstrated that 1 s duration erTDCS time-locked to the participants' reaching actions enhanced adaptation significantly better than sham. A close replication in the second study demonstrated 0.5 s erTDCS synchronous with the reaching actions again resulted in better adaptation than standard TDCS, significantly better than sham. Stimulation either during the inter-trial intervals between movements or after movement, during assessment of visual feedback, had no significant effect. Because short duration stimulation with rapid onset and offset is more readily perceived by the participants, we additionally show that a non-electrical vibrotactile stimulation of the scalp, presented with the same timing as the erTDCS, had no significant effect. CONCLUSIONS: We conclude that short duration, event related, anodal TDCS targeting the cerebellum enhances motor adaptation compared to the standard model. We discuss possible mechanisms of action and speculate on neural learning processes that may be involved.

Timing is everything: Event-related transcranial direct current stimulation improves motor adaptation.

BACKGROUND: There is a current discord between the foundational theories underpinning motor learning and how we currently apply transcranial direct current stimulation (TDCS): the former is dependent on tight coupling of events while the latter is conducted with very low temporal resolution. OBJECTIVE: Here we aimed to investigate the temporal specificity of stimulation by applying TDCS in short epochs, and coincidentally with movement, during a motor adaptation task. METHODS: Participants simultaneously adapted a reaching movement to two opposing velocity-dependent force-fields (clockwise and counter-clockwise), distinguished by a contextual leftward or rightward shift in the task display and cursor location respectively. Brief bouts (<3 s) of event-related TDCS (er-TDCS) were applied over M1 or the cerebellum during movements for only one of these learning contexts. RESULTS: We show that when short duration stimulation is applied to the cerebellum and yoked to movement, only those reaching movements performed simultaneously with stimulation are selectively enhanced, whilst similar and interleaved movements are left unaffected. We found no evidence of improved adaptation following M1 er-TDCS, as participants displayed equivalent levels of error during both stimulated and unstimulated movements. Similarly, participants in the sham stimulation group adapted comparably during left and right-shift trials. CONCLUSIONS: It is proposed that the coupling of cerebellar stimulation and movement influences timing-dependent (i.e. Hebbian-like) mechanisms of plasticity to facilitate enhanced learning in the stimulated context.

Residual errors in visuomotor adaptation persist despite extended motor preparation periods.

A consistent finding in sensorimotor adaptation is a persistent undershoot of full compensation, such that performance asymptotes with residual errors greater than seen at baseline. This behavior has been attributed to limiting factors within the implicit adaptation system, which reaches a suboptimal equilibrium between trial-by-trial learning and forgetting. However, recent research has suggested that allowing longer motor planning periods prior to movement eliminates these residual errors. The additional planning time allows required cognitive processes to be completed before movement onset, thus increasing accuracy. Here, we looked to extend these findings by investigating the relationship between increased motor preparation time and the size of imposed visuomotor rotation (30°, 45°, or 60°), with regard to the final asymptotic level of adaptation. We found that restricting preparation time to 0.35 s impaired adaptation for moderate and larger rotations, resulting in larger residual errors compared to groups with additional preparation time. However, we found that even extended preparation time failed to eliminate persistent errors, regardless of magnitude of cursor rotation. Thus, the asymptote of adaptation was significantly less than the degree of imposed rotation, for all experimental groups. In addition, there was a positive relationship between asymptotic error and implicit retention. These data suggest that a prolonged motor preparation period is insufficient to reliably achieve complete adaptation, and therefore, our results suggest that factors beyond that of planning time contribute to asymptotic adaptation levels.NEW & NOTEWORTHY Residual errors in sensorimotor adaptation are commonly attributed to an equilibrium between trial-by-trial learning and forgetting. Recent research suggested that allowing sufficient time for mental rotation eliminates these errors. In a number of experimental conditions, we show that although restricted motor preparation time does limit adaptation-consistent with mental rotation-extending preparation time fails to eliminate the residual errors in motor adaptation.

Direct and indirect effects of cathodal cerebellar TDCS on visuomotor adaptation of hand and arm movements.

Adaptation of movements involving the proximal and distal upper-limb can be differentially facilitated by anodal transcranial direct current stimulation (TDCS) over the cerebellum and primary motor cortex (M1). Here, we build on this evidence by demonstrating that cathodal TDCS impairs motor adaptation with a differentiation of the proximal and distal upper-limbs, relative to the site of stimulation. Healthy young adults received M1 or cerebellar cathodal TDCS while making fast 'shooting' movements towards targets under 60° rotated visual feedback conditions, using either whole-arm reaching or fine hand and finger movements. As predicted, we found that cathodal cerebellar TDCS resulted in impairment of adaptation of movements with the whole arm compared to M1 and sham groups, which proved significantly different during late adaptation. However, cathodal cerebellar TDCS also significantly enhanced adaptation of hand movements, which may reflect changes in the excitability of the pathway between the cerebellum and M1. We found no evidence for change of adaptation rates using arm or finger movements following cathodal TDCS directly over M1. These results are further evidence to support movement specific effects of TDCS, and highlight how the connectivity and functional organisation of the cerebellum and M1 must be considered when designing TDCS-based therapies.

Targeted tDCS selectively improves motor adaptation with the proximal and distal upper limb.

BACKGROUND: The cerebellum and primary motor cortex (M1) are crucial to coordinated and accurate movements of the upper limbs. There is also appreciable evidence that these two structures exert somewhat divergent influences upon proximal versus distal upper limb control. Here, we aimed to differentially regulate the contribution of the cerebellum and M1 to proximal and distal effectors during motor adaptation, with transcranial direct current stimulation (tDCS). For this, we employed tasks that promote similar motor demands, but isolate whole arm from hand/finger movements, in order to functionally segregate the hierarchy of upper limb control. METHODS: Both young and older adults took part in a visuomotor rotation task; where they adapted to a 60° visuomotor rotation using either a hand-held joystick (requiring finger/hand movements) or a 2D robotic manipulandum (requiring whole-arm reaching movements), while M1, cerebellar or sham tDCS was applied. RESULTS: We found that cerebellar stimulation improved adaptation performance when arm movements were required to complete the task, while in contrast stimulation of M1 enhanced adaptation during hand and finger movements only. This double-dissociation was replicated in an independent group of older adults, demonstrating that the behaviour remains intact in ageing. CONCLUSIONS: These results suggest that stimulation of distinct motor areas can selectively improve motor adaptation in the proximal and distal upper limb. This also highlights new ways in which tDCS might be best applied to achieve reliable rehabilitation of upper limb motor deficits.