Virtual Reality Action Observation and Motor Imagery to Enhance Neuroplastic Capacity in the Human Motor Cortex: A Pilot Double-blind, Randomized Cross-over Trial.

Neuroplasticity is important for learning, development and recovery from injury. Therapies that can upregulate neuroplasticity are therefore of interest across a range of fields. We developed a novel virtual reality action observation and motor imagery (VR-AOMI) intervention and evaluated whether it could enhance the efficacy of mechanisms of neuroplasticity in the human motor cortex of healthy adults. A secondary question was to explore predictors of the change in neuroplasticity following VR-AOMI. A pre-registered, pilot randomized controlled cross-over trial was performed. Twenty right-handed adults (13 females; mean age: 23.0 ±â€¯4.53 years) completed two experimental conditions in separate sessions; VR-AOMI and control. We used intermittent theta burst stimulation (iTBS) to induce long term potentiation-like plasticity in the motor cortex and recorded motor evoked potentials at multiple timepoints as a measure of corticospinal excitability. The VR-AOMI task did not significantly increase the change in MEP amplitude following iTBS when compared to the control task (Group × Timepoint interaction p = 0.17). However, regression analysis identified the change in iTBS response following VR-AOMI was significantly predicted by the baseline iTBS response in the control task. Specifically, participants that did not exhibit the expected increase in MEP amplitude following iTBS in the control condition appear to have greater excitability following iTBS in the VR-AOMI condition (r = -0.72, p < 0.001). Engaging in VR-AOMI might enhance capacity for neuroplasticity in some people who typically do not respond to iTBS. VR-AOMI may prime the brain for enhanced neuroplasticity in this sub-group.

Evaluating the influence of feedback on motor skill learning and motor performance for children with developmental coordination disorder: a systematic review.

Introduction: Children with developmental coordination disorder (DCD) have difficulties with learning and performing physical tasks. It is well known that task-specific practice is effective in improving motor skills. Additional feedback during practice may function as a quality improvement mechanism and therefore enhance motor skill outcomes. Aims: To investigate the effect of different forms of feedback on motor learning and motor performance in children with DCD. Methods: A systematic review was conducted (registration CRD42020175118) to investigate the effectiveness of different types of feedback, compared to other forms of feedback, or no additional feedback, on motor learning and motor performance outcomes in children with DCD. The search was run across six electronic databases (last search January 2024). Two reviewers independently screened studies for inclusion, assessed the quality of included studies, and extracted relevant data. A narrative synthesis was performed and included studies that assessed motor learning and/or performance outcomes following an intervention that delivered a specific form of feedback in comparison to another form of feedback or no specific feedback. Results: 14 articles from 13 trials were included in this review. Feedback was delivered by providing various forms of feedback, including: knowledge of results, focus of attention and augmented feedback delivered via technology. No significant differences were found between different forms of feedback for motor learning or performance outcomes for children with DCD. Interventions that used technology (with augmented feedback) to deliver the intervention were found to be as effective as traditional therapy. All groups who participated in therapy, regardless of the presence or type of feedback received, improved in overall scores on a motor performance outcome assessment. Conclusion: Despite the clear rationale for using feedback-oriented interventions for children with DCD, there is surprisingly limited and low-quality research. There is no clear evidence that one form of feedback is more effective than another, although it appears that feedback delivered via technology may be as effective as feedback delivered in traditional therapy interventions for children with DCD. Further exploration is required from appropriately powered and well-designed trials. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=175118, identifier (CRD42020175118).

Transcutaneous auricular vagus nerve stimulation modifies cortical excitability in middle-aged and older adults.

There is a growing interest in the clinical application of transcutaneous auricular vagus nerve stimulation (taVNS). However, its effect on cortical excitability, and whether this is modulated by stimulation duration, remains unclear. We evaluated whether taVNS can modify excitability in the primary motor cortex (M1) in middle-aged and older adults and whether the stimulation duration moderates this effect. In addition, we evaluated the blinding efficacy of a commonly reported sham method. In a double-blinded randomized cross-over sham-controlled study, 23 healthy adults (mean age 59.91 ± 6.87 years) received three conditions: active taVNS for 30 and 60 min and sham for 30 min. Single and paired-pulse transcranial magnetic stimulation was delivered over the right M1 to evaluate motor-evoked potentials. Adverse events, heart rate and blood pressure measures were evaluated. Participant blinding effectiveness was assessed via guesses about group allocation. There was an increase in short-interval intracortical inhibition (F = 7.006, p = .002) and a decrease in short-interval intracortical facilitation (F = 4.602, p = .014) after 60 min of taVNS, but not 30 min, compared to sham. taVNS was tolerable and safe. Heart rate and blood pressure were not modified by taVNS (p > .05). Overall, 96% of participants detected active stimulation and 22% detected sham stimulation. taVNS modifies cortical excitability in M1 and its effect depends on stimulation duration in middle-aged and older adults. taVNS increased GABAAergic inhibition and decreased glutamatergic activity. Sham taVNS protocol is credible but there is an imbalance in beliefs about group allocation.

Clinical application of transcutaneous auricular vagus nerve stimulation: a scoping review.

PURPOSE: Transcutaneous auricular vagus nerve stimulation (taVNS) is an emerging non-invasive neuromodulation therapy. This study aimed to explore the therapeutic use of taVNS, optimal stimulation parameters, effective sham protocols, and safety. METHODS: A scoping review was conducted. Five databases and grey literature were searched. The data extracted included stimulation parameters, adverse events (AEs), and therapeutic effects on clinical outcomes. RESULTS: 109 studies were included. taVNS was used across 21 different clinical populations, most commonly in psychiatric, cardiac, and neurological disorders. Overall, 2,214 adults received active taVNS and 1,017 received sham taVNS. Reporting of stimulation parameters was limited and inconsistent. taVNS appeared to have a favourable therapeutic effect across a wide range of clinical populations with varied parameters. Three sham protocols were reported but their effectiveness was documented in only two of the 54 sham-controlled studies. Most reported adverse events were localised to stimulation site. CONCLUSION: There is growing evidence for taVNS therapeutic effect. taVNS appears safe and tolerable. Sham protocols need evaluation. Standardised and comprehensive reporting of both stimulation parameters and adverse events is required. Two different questionnaires have been proposed to evaluate adverse events and the effectiveness of sham methods in blinding participants.

Transcutaneous auricular vagus nerve stimulation (taVNS) showed therapeutic effect across a wide range of clinical populations including depression, epilepsy, and strokeThere is a preliminary indication that daily/weekly dose and overall duration of treatment are important to show therapeutic effectivenessWhen using taVNS as an intervention, the questionnaires proposed in this review should be used to evaluate blinding effectiveness and adverse events.

Non-invasive brain stimulation in the treatment of post-stroke aphasia: a scoping review.

PURPOSE: Aphasia is an acquired language impairment that commonly results from stroke. Non-invasive brain stimulation (NIBS) might accelerate aphasia recovery trajectories and has seen mounting popularity in recent aphasia rehabilitation research. The present review aimed to: (1) summarise all existing literature on NIBS as a post-stroke aphasia treatment; and (2) provide recommendations for future NIBS-aphasia research. MATERIALS AND METHODS: Databases for published and grey literature were searched using scoping review methodology. 278 journal articles, conference abstracts/posters, and books, and 38 items of grey literature, were included for analysis. RESULTS: Quantitative analysis revealed that ipsilesional anodal transcranial direct current stimulation and contralesional 1-Hz repetitive transcranial magnetic stimulation were the most widely used forms of NIBS, while qualitative analysis identified four key themes including: the roles of the hemispheres in aphasia recovery and their relationship with NIBS; heterogeneity of individuals but homogeneity of subpopulations; individualisation of stimulation parameters; and much remains under-explored in the NIBS-aphasia literature. CONCLUSIONS: Taken together, these results highlighted systemic challenges across the field such as small sample sizes, inter-individual variability, lack of protocol optimisation/standardisation, and inadequate focus on aphasiology. Four key recommendations are outlined herein to guide future research and refine NIBS methods for post-stroke aphasia treatment.

A comprehensive review of non-invasive brain stimulation (NIBS) post-stroke aphasia literature, including all study designs, was required.Review of this literature revealed that anodal transcranial direct current stimulation is the mostly commonly used type of NIBS in aphasia treatment research.Systemic challenges across the field hinder prospective translation of NIBS into aphasia practice.Aphasia rehabilitation professionals should note that further research is required before NIBS is suitable for translation into clinical practice.

Data-driven biomarkers outperform theory-based biomarkers in predicting stroke motor outcomes.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have predicted motor outcomes based on the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to predict chronic motor outcomes after stroke and compares the accuracy of these predictions to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients (293 female/496 male) from the ENIGMA Stroke Recovery Working Group (age 64.9±18.0 years; time since stroke 12.2±0.2 months; normalised motor score 0.7±0.5 (range [0,1]). The out-of-sample prediction accuracy of two theory-based biomarkers was assessed: lesion load of the corticospinal tract, and lesion load of multiple descending motor tracts. These theory-based prediction accuracies were compared to the prediction accuracy from three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had better prediction accuracy - as measured by higher explained variance in chronic motor outcomes - than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R2 = 0.210, p < 0.001), performing significantly better than predictions using the theory-based biomarkers of lesion load of the corticospinal tract (R2 = 0.132, p< 0.001) and of multiple descending motor tracts (R2 = 0.180, p < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R2 =0.200, p < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R2 =0.167, p < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved prediction accuracy for theory-based and data-driven biomarkers. Finally, combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R2 = 0.241, p < 0.001. Overall, these results demonstrate that models that predict chronic motor outcomes using data-driven features, particularly when lesion data is represented in terms of structural disconnection, perform better than models that predict chronic motor outcomes using theory-based features from the motor system. However, combining both theory-based and data-driven models provides the best predictions.

Moderate intensity aerobic exercise may enhance neuroplasticity of the contralesional hemisphere after stroke: a randomised controlled study.

Upregulation of neuroplasticity might help maximize stroke recovery. One intervention that appears worthy of investigation is aerobic exercise. This study aimed to determine whether a single bout of moderate intensity aerobic exercise can enhance neuroplasticity in people with stroke. Participants were randomly assigned (1:1) to a 20-min moderate intensity exercise intervention or remained sedentary (control). Transcranial magnetic stimulation measured corticospinal excitability of the contralesional hemisphere by recording motor evoked potentials (MEPs). Intermittent Theta Burst Stimulation (iTBS) was used to repetitively activate synapses in the contralesional primary motor cortex, initiating the early stages of neuroplasticity and increasing excitability. It was surmised that if exercise increased neuroplasticity, there would be a greater facilitation of MEPs following iTBS. Thirty-three people with stroke participated in this study (aged 63.87 ± 10.30 years, 20 male, 6.13 ± 4.33 years since stroke). There was an interaction between Time*Group on MEP amplitudes (P = 0.009). Participants allocated to aerobic exercise had a stronger increase in MEP amplitude following iTBS. A non-significant trend indicated time since stroke might moderate this interaction (P = 0.055). Exploratory analysis suggested participants who were 2-7.5 years post stroke had a strong MEP facilitation following iTBS (P < 0.001). There was no effect of age, sex, resting motor threshold, self-reported physical activity levels, lesion volume or weighted lesion load (all P > 0.208). Moderate intensity cycling may enhance neuroplasticity in people with stroke. This therapy adjuvant could provide opportunities to maximize stroke recovery.

White Matter Integrity and Chronic Poststroke Upper Limb Function: An ENIGMA Stroke Recovery Analysis.

BACKGROUND: Integrity of the corticospinal tract (CST) is an important biomarker for upper limb motor function following stroke. However, when structurally compromised, other tracts may become relevant for compensation or recovery of function. METHODS: We used the ENIGMA Stroke Recovery data set, a multicenter, retrospective, and cross-sectional collection of patients with upper limb impairment during the chronic phase of stroke to test the relevance of tracts in individuals with less and more severe (laterality index of CST fractional anisotropy ≥0.25) CST damage in an observational study design. White matter integrity was quantified using fractional anisotropy for the CST, the superior longitudinal fascicle, and the callosal fibers interconnecting the primary motor cortices between hemispheres. Optic radiations served as a control tract as they have no a priori relevance for the motor system. Pearson correlation was used for testing correlation with upper limb motor function (Fugl-Meyer upper extremity). RESULTS: From 1235 available data sets, 166 were selected (by imaging, Fugl-Meyer upper extremity, covariates, stroke location, and stage) for analyses. Only individuals with severe CST damage showed a positive association of fractional anisotropy in both callosal fibers interconnecting the primary motor cortices (r[21]=0.49; P=0.025) and superior longitudinal fascicle (r[21]=0.51; P=0.018) with Fugl-Meyer upper extremity. CONCLUSIONS: Our data support the notion that individuals with more severe damage of the CST depend on residual pathways for achieving better upper limb outcome than those with less affected CST.

Quantifying patient experiences with therapeutic neurorehabilitation technologies: a scoping review.

PURPOSE: Neurorehabilitation technologies are a novel approach to providing rehabilitation for patients with neurological conditions. There is a need to explore patient experiences. This study aimed; 1) To identify available questionnaires that assess patients' experiences with neurorehabilitation technologies, and 2) where reported, to document the psychometric properties of the identified questionnaires. MATERIALS AND METHODS: Four databases were searched (Medline, Embase, Emcare and PsycInfo). The inclusion criteria were all types of primary data collection that included neurological patients of all ages who had experienced therapy with neurorehabilitation technologies and completed questionnaires to assess these experiences. RESULTS: Eighty-eight publications were included. Fifteen different questionnaires along with many self-developed scales were identified. These were categorised as; 1) self-developed tools, 2) specific questionnaire for a particular technology, and 3) generic questionnaires originally developed for a different purpose. The questionnaires were used to assess various technologies, including virtual reality, robotics, and gaming systems. Most studies did not report any psychometric properties. CONCLUSION: Many tools have been used to evaluate patient experiences, but few were specifically developed for neurorehabilitation technologies and psychometric data was limited. A preliminary recommendation would be use of the User Satisfaction Evaluation Questionnaire to evaluate patient experience with virtual reality systems.Implications for Rehabilitation:Fifteen unique tools evaluating patient experiences with neurorehabilitation technology were identifiedThe User Satisfaction Evaluation and ArmAssist Usability Assessment were designed specifically for therapeutic neurorehabilitation technologyFor all identified tools, psychometric data were poorly reported or not availableA preliminary recommendation is to use the User Satisfaction Evaluation Questionnaire for evaluating virtual reality systems.

Association of Brain Age, Lesion Volume, and Functional Outcome in Patients With Stroke.

BACKGROUND AND OBJECTIVES: Functional outcomes after stroke are strongly related to focal injury measures. However, the role of global brain health is less clear. In this study, we examined the impact of brain age, a measure of neurobiological aging derived from whole-brain structural neuroimaging, on poststroke outcomes, with a focus on sensorimotor performance. We hypothesized that more lesion damage would result in older brain age, which would in turn be associated with poorer outcomes. Related, we expected that brain age would mediate the relationship between lesion damage and outcomes. Finally, we hypothesized that structural brain resilience, which we define in the context of stroke as younger brain age given matched lesion damage, would differentiate people with good vs poor outcomes. METHODS: We conducted a cross-sectional observational study using a multisite dataset of 3-dimensional brain structural MRIs and clinical measures from the ENIGMA Stroke Recovery. Brain age was calculated from 77 neuroanatomical features using a ridge regression model trained and validated on 4,314 healthy controls. We performed a 3-step mediation analysis with robust mixed-effects linear regression models to examine relationships between brain age, lesion damage, and stroke outcomes. We used propensity score matching and logistic regression to examine whether brain resilience predicts good vs poor outcomes in patients with matched lesion damage. RESULTS: We examined 963 patients across 38 cohorts. Greater lesion damage was associated with older brain age (ß = 0.21; 95% CI 0.04-0.38, p = 0.015), which in turn was associated with poorer outcomes, both in the sensorimotor domain (ß = -0.28; 95% CI -0.41 to -0.15, p < 0.001) and across multiple domains of function (ß = -0.14; 95% CI -0.22 to -0.06, p < 0.001). Brain age mediated 15% of the impact of lesion damage on sensorimotor performance (95% CI 3%-58%, p = 0.01). Greater brain resilience explained why people have better outcomes, given matched lesion damage (odds ratio 1.04, 95% CI 1.01-1.08, p = 0.004). DISCUSSION: We provide evidence that younger brain age is associated with superior poststroke outcomes and modifies the impact of focal damage. The inclusion of imaging-based assessments of brain age and brain resilience may improve the prediction of poststroke outcomes compared with focal injury measures alone, opening new possibilities for potential therapeutic targets.

Do age-related differences in aperiodic neural activity explain differences in resting EEG alpha?

Alpha-band oscillatory activity in human electroencephalography (EEG) becomes slower and lower in amplitude with advanced age. However, the influence of aperiodic activity on these measures has received little consideration. We investigated whether age-related differences in aperiodic activity explains differences in resting EEG peak alpha frequency and power. We assessed aperiodic activity in 85 younger and 92 older adults by fitting the 1/f-like background activity evident in EEG power spectra using the spectral parameterization ("specparam") algorithm. Across the scalp, the aperiodic exponent and offset were smaller in older compared to younger participants, reflecting a flatter 1/f-like slope and a downward broadband shift in power spectra with age. After correcting for aperiodic activity, peak alpha frequency remained slower in older adults; however, peak alpha power no longer differed statistically between age groups. The large sample size utilized in this study, as well as the depth of analysis, provides further evidence that the aperiodic component of the resting EEG signal is altered with aging and should be considered when investigating neural oscillatory activity.

Sex Differences in Spatiotemporal Gait Parameters of Transtibial Amputees.

Research addressing lower limb amputee gait and prosthetic design often focuses on men, despite female lower limb amputees having different risk factors and lower success with their prosthetics overall. It is widely agreed that sex differences exist in able-bodied gait, but research analyzing sex differences in amputee gait is rare. This study compared male and female transtibial amputee gait to ascertain potential sex differences. Forty-five transtibial amputees were asked to walk at their self-selected speed, and spatiotemporal gait data were obtained. Both the mean and variability metric of parameters were analyzed for 10 male and 10 female participants. For all participants, amputated limbs had a shorter stance time, longer swing time, and larger step length. Females had a 10% shorter stance time and 26% larger normalized step and stride length than males. Female participants also walked over 20% faster than male participants. Finally, significant interactions were found in the mean and variability metric of stride velocity, indicating greater variability in women. These findings suggest that sex differences exist in transtibial amputee gait, offering possible explanations for the different comorbidities experienced by female lower limb amputees. These results have major implications for female amputees and for sex-specific research, rehabilitation, and prosthetic design.

Safety and Adverse Events following Non-invasive Electrical Brain Stimulation in Stroke: A Systematic Review.

BACKGROUND: Noninvasive electrical stimulation (ES) could have therapeutic potential in stroke recovery. However, there is no comprehensive evaluation of adverse events. This study systematically searched the literature to document frequency and prevalence of adverse events. A secondary aim was to explore associations between adverse events and ES parameters or participant characteristics.Methods: Databases were searched for studies evaluating ES in adults with stroke. All included studies were required to report on adverse events. Extracted data were: (1) study design; (2) adverse events; (3) participant characteristics; (4) ES parameters. RESULTS: Seventy-five studies were included. Adverse events were minor in nature. The most frequently reported adverse events were tingling (37.3% of papers), burning (18.7%), headaches (14.7%) and fatigue (14.7%). Cathodal stimulation was associated with greater frequency of itching (p = .02), intensities of 1-2 mA with increased tingling (p = .04) and discomfort (p = .03), and current density <0.4mA/cm2 with greater discomfort (p = .03). Tingling was the most prevalent adverse event (18.1% of participants), with prevalence data not differing between active and control conditions (all p ≥ 0.37). Individual participants were more likely to report adverse events with increasing current density (r = 0.99, p = .001). Two severe adverse events were noted (a seizure and percutaneous endoscopic gastrostomy placement). CONCLUSION: ES appears safe in people with stroke as reported adverse events were predominantly minor in nature. An adverse events questionnaire is proposed to enable a more comprehensive and nuanced analysis of the frequency and prevalence of adverse events.

Key constructs of body awareness impairments post-stroke: a scoping review of assessment tools and interventions.

PURPOSE: To summarise body awareness assessment tools and interventions relevant for stroke rehabilitation using a framework that categorises key body awareness constructs, disorders and impairments. MATERIALS AND METHODS: Online electronic databases and trial registries were searched from inception until July 2021, in addition to hand searching reference lists of included studies and reviews. Study selection included any study design where the investigation involved assessing and/or intervening in body awareness following stroke. Data were extracted based on predefined criteria by two independent reviewers and mapped to the emergent framework. RESULTS: The final analysis included 144 papers that reported 43 assessment tools and 8 types of interventions for body awareness. Consensus was reached on a synthesised body awareness framework. This comprised specific impairments and disorders, constructs, sub-categories and main categories leading to the overarching term of body awareness. Clinical and psychometric properties of the assessment tools were not reported or poorly evaluated, and the interventions lacked robust study designs and rigorous methods. CONCLUSIONS: The framework produced will enable future research and clinical practice to be based on consistent concepts and definitions. Clinicians can also use this information to cautiously select assessment tools and/or interventions but are reminded of the limitations identified in this review.Implications for rehabilitationThere is limited understanding, compounded by inconsistent terminology and definitions regarding body awareness after stroke.A synthesized framework to define key constructs and definitions of body awareness is proposed.Assessment tools and interventions reported in the literature are mapped to the proposed framework.Psychometric properties of available tools are reported.Significant work remains to refine concepts of body awareness, develop and evaluate assessment tools and interventions.

Revisiting dose and intensity of training: Opportunities to enhance recovery following stroke.

PURPOSE: Stroke is a global leading cause of adult disability with survivors often enduring persistent impairments and loss of function. Both intensity and dosage of training appear to be important factors to help restore behavior. However, current practice fails to achieve sufficient intensity and dose of training to promote meaningful recovery. The purpose of this review is to propose therapeutic solutions that can help achieve a higher dose and/or intensity of therapy. Raising awareness of these intensive, high-dose, treatment strategies might encourage clinicians to re-evaluate current practice and optimize delivery of stroke rehabilitation for maximal recovery. METHODS: Literature that tested and evaluated solutions to increase dose or intensity of training was reviewed. For each therapeutic strategy, we outline evidence of clinical benefit, supporting neurophysiological data (where available) and discuss feasibility of clinical implementation. RESULTS: Possible therapeutic solutions included constraint induced movement therapy, robotics, circuit therapy, bursts of training, gaming technologies, goal-oriented instructions, and cardiovascular exercise. CONCLUSION: Our view is that clinicians should evaluate current practice to determine how intensive high-dose training can be implemented to promote greater recovery after stroke.

Extended Repetitive Transcranial Magnetic Stimulation Therapy for Post-stroke Depression in a Patient With a Pre-frontal Cortical Lesion: A Case Study.

Approximately one-third of stroke survivors experience post-stroke depression. Repetitive transcranial magnetic stimulation (rTMS) of the prefrontal cortex has shown promise as a treatment for depression with few side effects and high tolerability. However, previous post-stroke depression trials have not considered the effect of lesion location, the persistence of clinical improvements, nor the value of ongoing maintenance treatments. These questions are important to determine the therapeutic value of rTMS as a treatment for post-stroke depression. We report a unique case study of a 71-year-old male who had experienced a left hemispheric ischemic stroke 4 years prior. The patient was screened with the Beck Depression Inventory and Patient Health Questionnaire and found to be experiencing moderate levels of depression. Ten daily sessions of left dorsolateral pre-frontal cortex rTMS were applied over a two-week period. A clinically meaningful reduction in depression was achieved. Approximately 10 weeks following rTMS treatment, improvements in depression were attenuating. Weekly maintenance rTMS was delivered to the left dorsolateral pre-frontal cortex for 10 sessions. At the conclusion of maintenance rTMS, clinical assessments indicated depressive symptoms had reduced to a minimal to nil level. Clinically meaningful improvements in depression were maintained at 3 months after rTMS treatment had ceased. These findings provide novel insight to suggest rTMS may reduce depressive symptoms in stroke survivors with a lesion at the site of stimulation. Ongoing maintenance treatments might prove beneficial to enhance persistence of clinical improvements.

A large, curated, open-source stroke neuroimaging dataset to improve lesion segmentation algorithms.

Accurate lesion segmentation is critical in stroke rehabilitation research for the quantification of lesion burden and accurate image processing. Current automated lesion segmentation methods for T1-weighted (T1w) MRIs, commonly used in stroke research, lack accuracy and reliability. Manual segmentation remains the gold standard, but it is time-consuming, subjective, and requires neuroanatomical expertise. We previously released an open-source dataset of stroke T1w MRIs and manually-segmented lesion masks (ATLAS v1.2, N = 304) to encourage the development of better algorithms. However, many methods developed with ATLAS v1.2 report low accuracy, are not publicly accessible or are improperly validated, limiting their utility to the field. Here we present ATLAS v2.0 (N = 1271), a larger dataset of T1w MRIs and manually segmented lesion masks that includes training (n = 655), test (hidden masks, n = 300), and generalizability (hidden MRIs and masks, n = 316) datasets. Algorithm development using this larger sample should lead to more robust solutions; the hidden datasets allow for unbiased performance evaluation via segmentation challenges. We anticipate that ATLAS v2.0 will lead to improved algorithms, facilitating large-scale stroke research.

Chronic Stroke Sensorimotor Impairment Is Related to Smaller Hippocampal Volumes: An ENIGMA Analysis.

Background Persistent sensorimotor impairments after stroke can negatively impact quality of life. The hippocampus is vulnerable to poststroke secondary degeneration and is involved in sensorimotor behavior but has not been widely studied within the context of poststroke upper-limb sensorimotor impairment. We investigated associations between non-lesioned hippocampal volume and upper limb sensorimotor impairment in people with chronic stroke, hypothesizing that smaller ipsilesional hippocampal volumes would be associated with greater sensorimotor impairment. Methods and Results Cross-sectional T1-weighted magnetic resonance images of the brain were pooled from 357 participants with chronic stroke from 18 research cohorts of the ENIGMA (Enhancing NeuoImaging Genetics through Meta-Analysis) Stroke Recovery Working Group. Sensorimotor impairment was estimated from the FMA-UE (Fugl-Meyer Assessment of Upper Extremity). Robust mixed-effects linear models were used to test associations between poststroke sensorimotor impairment and hippocampal volumes (ipsilesional and contralesional separately; Bonferroni-corrected, P<0.025), controlling for age, sex, lesion volume, and lesioned hemisphere. In exploratory analyses, we tested for a sensorimotor impairment and sex interaction and relationships between lesion volume, sensorimotor damage, and hippocampal volume. Greater sensorimotor impairment was significantly associated with ipsilesional (P=0.005; ß=0.16) but not contralesional (P=0.96; ß=0.003) hippocampal volume, independent of lesion volume and other covariates (P=0.001; ß=0.26). Women showed progressively worsening sensorimotor impairment with smaller ipsilesional (P=0.008; ß=-0.26) and contralesional (P=0.006; ß=-0.27) hippocampal volumes compared with men. Hippocampal volume was associated with lesion size (P<0.001; ß=-0.21) and extent of sensorimotor damage (P=0.003; ß=-0.15). Conclusions The present study identifies novel associations between chronic poststroke sensorimotor impairment and ipsilesional hippocampal volume that are not caused by lesion size and may be stronger in women.

Resting-state Networks in Tinnitus : A Scoping Review.

Chronic subjective tinnitus is the constant perception of a sound that has no physical source. Brain imaging studies show alterations in tinnitus patients' resting-state networks (RSNs). This scoping review aims to provide an overview of resting-state fMRI studies in tinnitus, and to evaluate the evidence for changes in different RSNs. A total of 29 studies were included, 26 of which found alterations in networks such as the auditory network, default mode network, attention networks, and visual network; however, there is a lack of reproducibility in the field which can be attributed to the use of different regions of interest and analytical methods per study, and tinnitus heterogeneity. Future studies should focus on replication by using the same regions of interest in their analysis of resting-state data, and by controlling adequately for potential confounds. These efforts could potentially lead to the identification of a biomarker for tinnitus in the future.

Cognitive Reserve Modifies the Relationship Between Neural Function, Neural Injury and Upper-Limb Recovery After Stroke.

OBJECTIVE: To investigate whether cognitive reserve modifies the relationship between functional connectivity, lesion volume, stroke severity and upper-limb motor impairment and recovery in stroke survivors. METHODS: Ten patients with first-ever ischemic middle cerebral artery stroke completed the Cognitive Reserve Index Questionnaire at baseline. Upper-limb motor impairment and functional connectivity were assessed using the Fugl-Meyer Assessment and electroencephalography respectively at baseline and 3-months post-stroke. A debiased weighted phase lag index was computed to estimate functional connectivity between electrodes. Partial least squares (PLS) regression identified a connectivity model that maximally predicted variance in the degree of upper-limb impairment. Regression models were generated to determine whether cognitive reserve modified the relationship between neural function (functional connectivity), neural injury (lesion volume), stroke severity (National Institutes of Health Stroke Scale) and upper-limb motor impairment at baseline and recovery at 3-months (Fugl-Meyer Assessment). RESULTS: The addition of cognitive reserve to a regression model with a dependent variable of upper-limb motor recovery and independent variables of functional connectivity between the ipsilesional motor cortex and parietal cortex, stroke severity and lesion volume improved model efficiency (∆BIC=-7.07) despite not reaching statistical significance (R2=0.90, p=0.07). Cognitive reserve did not appear to improve regression models examining motor impairment at baseline. CONCLUSIONS: Preliminary observations suggest cognitive reserve might modify the relationship between neural function, neural injury, stroke severity and upper-limb motor recovery. Further investigation of cognitive reserve in motor recovery post-stroke appears warranted.