Abstract Background Transcranial direct current stimulation (tDCS) is increasingly used as an adjunct to rehabilitation for young people with cerebral palsy (CP), yet considerable variability exists in clinical response. Individualised electric field modelling provides an opportunity to estimate the distribution of electrical fields generated by the stimulation delivered to the brain and explore potential relationships with functional outcomes. Methods Structural MRI scans from nineteen participants (10-16 years) from a previously published randomised controlled trial ( ISRCTN74235136 ) investigating the effects of tDCS combined with motor training, underwent participant-specific finite element modelling using SimNIBS. Electric field strength was quantified within anatomically defined motor regions of interest, including the primary motor cortex (M1), dorsal premotor cortex (PMd), supplementary motor area (SMA), and a combined motor network. Global grey matter electric field metrics and stimulation focality were also extracted. Results Estimated electric field strength differed significantly across motor regions (p<0.001), with PMd receiving significantly greater stimulation than both M1 and SMA. Electric field strength within a control region (primary visual cortex) was significantly lower than within M1 (p<0.001). Despite inter-individual variability in regional and global electric field metrics, no significant associations were observed between estimated electric field strength or focality and changes in function following intervention. Conclusion Individualised electric field modelling demonstrated that an M1-targeted tDCS montage preferentially stimulated PMd rather than M1 in young people with CP. These findings highlight the importance of subject-specific modelling when characterising current distribution and suggest that variability in electric field strength alone does not explain variability in behavioural response. Highlights Individualised modelling characterised tDCS electric fields in paediatric CP. M1-targeted tDCS produced greater electric field strength in PMd than M1. Motor regions received greater electric field strength than control visual cortex. Electric field strength did not predict upper- or lower-limb functional change.

Objectives: Non-invasive brain stimulation (NIBS) holds significant promise for treating neurological and neuropsychiatric conditions, yet translation into routine clinical practice remains limited. We aimed to explore stakeholder perceptions of NIBS and barriers to its clinical adoption. Methods: We conducted focus‑group interviews with 33 participants across three key stakeholder groups in the UK: (1) people with lived experience of brain injury, depression, or dementia; (2) healthcare professionals; and (3) researchers. Reflexive thematic analysis was used to identify themes in the data. Findings: Seven key themes emerged spanning preferences, hope and disappointment, communication, accessibility, infrastructure, ethical/regulatory uncertainty, and the evidence base. Across groups, NIBS was viewed positively and with cautious optimism, but substantial barriers were highlighted, including limited public and clinical awareness, challenges in demonstrating cost-effectiveness, infrastructure constraints, and difficulties navigating regulatory and translational pathways. Participants emphasised the importance of clear communication, improved education, and stronger interdisciplinary collaboration to support adoption. Notably, stakeholders prioritised evidence of clinical efficacy and usability over detailed mechanistic understanding. Conclusions: These findings provide actionable insights into the translational gap in NIBS and highlight priorities for facilitating its integration into clinical care.

Sleep disturbance is common but often overlooked after stroke. Regular sleep is increasingly recognised as important for overall health, yet little is known about how sleep regularity changes after stroke. This study examined differences in the Sleep Regularity Index (SRI) between stroke survivors and healthy controls using actigraphy data from an existing dataset (~ 1 week per participant). Data were analysed for 162 stroke survivors (mean age 61 ± 14 years, 5 ± 5 years post-stroke, 89 males) and 60 controls (mean age 57 ± 17 years, 32 males). Stroke survivors had significantly lower SRI scores than controls (p = 0.001), indicating less regular sleep. In the stroke group, higher SRI correlated with longer total sleep time (p = 0.003) and better self-reported sleep quality (p = 0.001) but not with other sleep metrics. Lower SRI was associated with worse depressive symptoms (p = 0.006) and lower quality of life (p = 0.001) but not with disability (p = 0.886) or time since stroke (p = 0.646). These findings suggest that sleep regularity is disrupted post-stroke and may influence well-being. Future research should explore interventions to improve sleep regularity and related health outcomes in stroke survivors.

Sleep is often disrupted after stroke. However, little is known about how stroke lesion extent or location influences sleep, particularly at the chronic stage of recovery. In this pragmatic study, we aimed to explore whether lesion characteristics could explain sleep variability in chronic stroke survivors. We analysed previously collected structural brain images (Magnetic Resonance Imaging) from 38 stroke participants (11 female, mean (SD) age 64 (12), mean (SD) time since stroke 95 (66) months) and sleep data (questionnaires (N=38, actigraphy (N=37), and electrophysiology (N=18)) which were collected in their home environment. Neither lesion volume nor lesion overlap with regions of interest (brainstem, basal ganglia, amygdala, hippocampus, thalamus) significantly predicted interindividual variability in subjective or objective sleep measures. However, a data-driven approach revealed clusters of voxels disconnected by the stroke lesions were linked to lower spindle density and amplitude (threshold free cluster enhancement p < 0.050). Overall, these results provide preliminary insights that lesion induced brain disconnection, rather than the extent and overlap of the lesion with grey matter regions, may be more informative when explaining sleep variability. However, larger prospective studies are needed to fully understand the effect of stroke lesions on sleep. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work is supported by the Wellcome Trust and the NIHR Oxford Health Biomedical Research Centre (NIHR203316). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. MKF is Funded by Guarantors of Brain and HJB is funded by the Wellcome Trust (222446/Z/21/Z). CJS holds a Senior Research Fellowship, funded by the Wellcome Trust (224430/Z/21/Z). The Wellcome Centre for Integrative Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z and 203139/A/16/Z). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Central University Research Ethics Committee, University of Oxford (reference R85306) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data derivatives and analysis scripts will be made available here: https://osf.io/vbu7c/. Raw data are available upon reasonable request from the corresponding author.

PURPOSE:Cerebral Palsy (CP) is the commonest cause of childhood motor disability. Transcranial direct current stimulation (tDCS) is a promising adjuvant therapy, but research targeting upper and lower limbs simultaneously is needed. We aimed to pilot tDCS with upper/lower limb motor training, estimate the potential effect on motor function, and investigate brain imaging correlates of function. MATERIALS AND METHODS:Participants (10-16 years) with CP affecting upper and/or lower limbs were randomised (online software) to 10 sessions of active (n = 14) or sham (n = 13) tDCS combined with motor training. The primary outcomes were upper and lower limb function assessed at 1-week post-intervention using the Jebson Taylor hand function (JTT) and Timed Up and Go (TUG) tests. Secondary, imaging outcomes included baseline tractography, grey matter volume, and resting state connectivity. RESULTS:Adherence was good: 74% completed all intervention sessions, 100% completed the primary outcome assessment. There were no between-group differences (1-week post-intervention, intention-to-treat; group-by-time JTT: F(1,25)=1.189,p = 0.286, partial-eta-squared = 0.05; TUG: F(1,25)=1.605,p = 0.217, partial-eta-squared = 0.06). Imaging showed subtle associations between better JTT at baseline and higher grey matter volume (caudate nucleus) and stronger sensorimotor resting state connectivity. CONCLUSIONS:The trial was well tolerated, but effect sizes were small. Larger studies are needed to further explore tDCS for CP.

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.

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.

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.

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 par-ticipants, 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. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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.

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 behaviour has been attributed to limiting factors within the implicit adaptation system, which reaches a sub-optimal 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 regards to the final asymptotic level of adaptation. We found that restricting preparation time to 0.35 seconds 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. Additionally, 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 provide support for the proposal that limitations within the implicit learning system contributes 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 while restricted motor preparation time does limit adaptation - consistent with mental rotation - extending preparation time fails to eliminate the residual errors in motor adaptation.

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.

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.

The control of proximal versus distal upper limb movements are believed to be subserved by somewhat distinct neural pathways. Direct connections from the primary motor cortex (M1) to distal muscles supports the key role of M1 in the production and control of hand/finger movements. Alternatively, impaired reach behaviour after cerebellar lesions and ataxia point to the cerebellum as a vital neural substrate contributing to whole arm reaching. Here, we aimed to further elucidate the roles of both the cerebellum and M1 during specific motor tasks using either movements of the hand and fingers or the whole arm. Young healthy participants received anodal transcranial direct current stimulation (TDCS) over the lateral cerebellum, M1 or sham stimulation during a visuomotor rotation task requiring either hand/finger movements or whole arm reaching movements. It was found that cerebellar TDCS enhanced adaptation for participants completing the reaching task, as they displayed significantly reduced error at the end of the task compared to the M1 or sham group. Conversely, M1 stimulation resulted in improved adaptation performance during the hand task compared to cerebellar or sham groups. These results demonstrate an effector specific effect of TDCS over M1 and the cerebellum during visuomotor adaptation.