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Stroke is a leading cause of serious long-term disability in adults and is the second leading cause of death worldwide. Early reperfusion and neuroprotection techniques have been the focus of much effort with the aim of very acute treatment of the stroke. Targeting different mechanisms, pharmacological therapies have the potential to reduce disability in a large fraction of patients who survive the acute stroke. The brain's capacity to reorganize after stroke through plasticity mechanisms can be modulated by pharmacological agents. A number of therapeutic interventions are under study, including small molecules, growth factors, and monoclonal antibodies. Recently it has been shown that the SSRI fluoxetine improved motor deficit in patients with ischaemic stroke and hemiplegia which appeared to be independent of the presence of depression. In this context, it is of major importance to support innovative research in order to promote the emergence of new pharmacological treatments targeting neurological recovery after stroke, as opposed to acute de-occlusion and neuroprotection. This paper is the work of a group of 14 scientists with aim of (1) addressing key areas of the basic and clinical aspects of human brain plasticity after stroke and potential pharmacological targets for recovery, (2) asking questions about the most appropriate characteristics of clinical trials testing drugs in post stroke recovery and (3) proposing recommendations for future clinical trials.

Purpose: To propose a consensus-based definition and framework for motor rehabilitation after stroke., Methods: An expert European working group reviewed the literature, attaining internal consensus after external feedback., Findings: Motor rehabilitation is defined as a process that engages people with stroke to benefit their motor function, activity capacity and performance in daily life. It is necessary for people with residual motor disability whose goal is to enhance their functioning, independence and participation. Motor rehabilitation operates through learning- and use-dependent mechanisms. The trajectory of motor recovery varies across patients and stages of recovery. Early behavioral restitution of motor function depends on spontaneous biological mechanisms. Further improvements in activities of daily living are achieved by compensations. Motor rehabilitation is guided by regular assessment of motor function and activity using consensus-based measures, including patient-reported outcomes. Results are discussed with the patient and their carers to set personal goals. During motor rehabilitation patients learn to optimize and adapt their motor, sensory and cognitive functioning through appropriately dosed repetitive, goal-oriented, progressive, task- and context-specific training. Motor rehabilitation supports people with stroke to maximize health, well-being and quality of life. The framework describes the International Classification of Functioning, Disability and Health in the context of stroke, describes neurobiological mechanisms of behavioral restitution and compensation, and summarizes recommendations for clinical assessment, prediction tools, and motor interventions with strong recommendations from clinical practice guidelines (2016-2022)., Conclusions: This definition and framework may guide clinical educators, inform clinicians on current recommendations and guidelines, and identify gaps in the evidence base., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Atlas-based voxel features have the potential to aid motor outcome prognostication after stroke, but are seldom used in clinically feasible prediction models. This could be because neuroimaging feature development is a non-standardized, complex, multistep process. This is a barrier to entry for researchers and poses issues for reproducibility and validation in a field of research where sample sizes are typically small., Objectives: The primary aim of this review is to describe the methodologies currently used in motor outcome prediction studies using atlas-based voxel neuroimaging features. Another aim is to identify neuroanatomical regions commonly used for motor outcome prediction., Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol was constructed and OVID Medline and Scopus databases were searched for relevant studies. The studies were then screened and details about imaging modality, image acquisition, image normalization, lesion segmentation, region of interest determination, and imaging measures were extracted., Results: Seventeen studies were included and examined. Common limitations were a lack of detailed reporting on image acquisition and the specific brain templates used for normalization and a lack of clear reasoning behind the atlas or imaging measure selection. A wide variety of sensorimotor regions relate to motor outcomes and there is no consensus use of one single sensorimotor atlas for motor outcome prediction., Conclusion: There is an ongoing need to validate imaging predictors and further improve methodological techniques and reporting standards in neuroimaging feature development for motor outcome prediction post-stroke.

The proportional recovery rule (PRR) posits that most stroke survivors can expect to reduce a fixed proportion of their motor impairment. As a statistical model, the PRR explicitly relates change scores to baseline values - an approach that arises in many scientific domains but has the potential to introduce artifacts and flawed conclusions. We describe approaches that can assess associations between baseline and changes from baseline while avoiding artifacts due either to mathematical coupling or to regression to the mean. We also describe methods that can compare different biological models of recovery. Across several real datasets in stroke recovery, we find evidence for non-artifactual associations between baseline and change, and support for the PRR compared to alternative models. We also introduce a statistical perspective that can be used to assess future models. We conclude that the PRR remains a biologically relevant model of stroke recovery., Competing Interests: JG, TK, AG, RK, AL, CS, WB, GK, JK No competing interests declared, (© 2022, Goldsmith et al.)

Fecal incontinence (FI) substantially impairs quality of life and imparts a major socioeconomic burden. Anal sphincter injury and possibly pudendal nerve damage are considered common causes, however, current clinical methods for evaluating their function remain suboptimal. Electromyography (EMG) and pudendal nerve terminal latencies have been applied with some success, but are not considered standard practice due to uncertain accuracy and clinical value. In this study we developed and applied a novel anorectal high-density (HD) EMG probe in humans and pigs to acquire quantitative electrophysiological metrics of the anorectum. In the human trial we assessed somatic pathways and showed that EMG amplitude was greater for tight voluntary squeezes than light voluntary squeezes (0.03 ± 0.02 mV vs. 0.05 ± 0.03 mV). In a porcine model we applied trans-sacral magnetic stimulation to evoke extrinsically activated involuntary pathways and the resulting motor evoked potentials (MEP) were captured using the HD-EMG probe. The mean MEP amplitude at 50% magnetic stimulation intensity output (MSO) was significantly lower that the MEP amplitude at 85, 95 and 100% MSO (1.52 ± 0.50 mV vs. 3.10 ± 0.60 mV). In conclusion, the use of HD-EMG probe in conjunction with trans-sacral magnetic stimulation, for spatiotemporal mapping of anorectal EMG and MEP activity is anticipated to achieve new insights into FI and could offer improved diagnostic and prognostic biomarkers for anorectal dysfunction.

Background: Motor outcomes after stroke can be predicted using structural and functional biomarkers of the descending corticomotor pathway, typically measured using magnetic resonance imaging and transcranial magnetic stimulation, respectively. However, the precise structural determinants of intact corticomotor function are unknown. Identifying structure-function links in the corticomotor pathway could provide valuable insight into the mechanisms of post-stroke motor impairment. This study used supervised machine learning to classify upper limb motor evoked potential status using MRI metrics obtained early after stroke., Methods: Retrospective data from 91 patients (49 women, age 35-97 years) with moderate to severe upper limb weakness within a week after stroke were included in this study. Support vector machine classifiers were trained using metrics from T1- and diffusion-weighted MRI to classify motor evoked potential status, empirically measured using transcranial magnetic stimulation., Results: Support vector machine classification of motor evoked potential status was 81% accurate, with false positives more common than false negatives. Important structural MRI metrics included diffusion anisotropy asymmetry in the supplementary and pre-supplementary motor tracts, maximum cross-sectional lesion overlap in the sensorimotor tract and ventral premotor tract, and mean diffusivity asymmetry in the posterior limbs of the internal capsule., Interpretations: MRI measures of corticomotor structure are good but imperfect predictors of corticomotor function. Residual corticomotor function after stroke depends on both the extent of cross-sectional macrostructural tract damage and preservation of white-matter microstructural integrity. Analysing the corticomotor pathway using a multivariable MRI approach across multiple tracts may yield more information than univariate biomarker analyses., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Rehabilitation is recognised as a cornerstone of multidisciplinary stroke care. Intensity of therapy is related to functional recovery although there is high variability on the amount of time and techniques applied in therapy sessions. There is a need to better describe stroke rehabilitation protocols to develop a better understanding of current practice increasing the internal validity and generalisation of clinical trial results. The aim of this study is to describe an intensive rehabilitation programme for patients with stroke in an inpatient rehabilitation facility, measuring the amount and type of therapies (physical, occupational and speech therapy) provided and reporting functional outcomes., Methods and Analysis: This will be a prospective observational cohort study of patients with subacute stroke admitted to our inpatient rehabilitation facility during 2 years. A therapy recording tool was developed in order to describe the rehabilitation interventions performed in our unit. This tool was designed using the Delphi method, literature search and collaboration with senior clinicians. Therapists will record the time spent on different activities available in our unit during specific therapy sessions. Afterwards, the total time spent in each activity, and the total rehabilitation time for all activities, will be averaged for all patients. Outcome variables were divided into three different domains: body structure and function outcomes, activity outcomes and participation outcomes and will be assessed at baseline (admission at the rehabilitation unit), at discharge from the rehabilitation unit and at 3 and 6 months after stroke., Ethics and Dissemination: This study was approved by the Medical Research Committee at Hospital del Mar Research Institute (Project ID: 34/C/2017). The results of this study will be presented at national and international congress and submitted for publication in peer-reviewed journals., Trial Registration Number: NCT04191109., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Response inhibition is a crucial component of executive control. Although mainly studied in upper limb tasks, it is fully implicated in gait initiation. Here, we assessed the influence of proactive and reactive inhibitory control during gait initiation in healthy adult participants. For this purpose, we measured kinematics and electroencephalography (EEG) activity (event-related potential [ERP] and time-frequency data) during a modified Go/NoGo gait initiation task in 23 healthy adults. The task comprised Go-certain, Go-uncertain, and NoGo conditions. Each trial included preparatory and imperative stimuli. Our results showed that go-uncertainty resulted in delayed reaction time, without any difference for the other parameters of gait initiation. Proactive inhibition, that is, Go uncertain versus Go certain conditions, influenced EEG activity as soon as the preparatory stimulus. Moreover, both proactive and reactive inhibition influenced the amplitude of the ERPs (central P1, occipito-parietal N1, and N2/P3) and theta and alpha/low beta band activities in response to the imperative-Go-uncertain versus Go-certain and NoGo versus Go-uncertain-stimuli. These findings demonstrate that the uncertainty context; induced proactive inhibition, as reflected in delayed gait initiation. Proactive and reactive inhibition elicited extended and overlapping modulations of ERP and time-frequency activities. This study shows the protracted influence of inhibitory control in gait initiation., (© 2024 The Author(s). Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Behavioural experiences interact with regenerative responses to shape patterns of neural reorganization after stroke. This review is focused on the competitive nature of these behavioural experience effects. Interactions between learning-related plasticity and regenerative reactions have been found to underlie the establishment of new compensatory behaviours and the efficacy of motor rehabilitative training in rodent stroke models. Learning in intact brains depends on competitive and cooperative mechanisms of synaptic plasticity. Synapses are added in response to learning and selectively maintained and strengthened via activity-dependent competition. Long-term memories for experiences that occur closely in time can be weakened or enhanced by competitive or cooperative interactions in the time-dependent process of stabilizing synaptic changes. Rodent stroke model findings suggest that compensatory reliance on the non-paretic hand after stroke can shape and stabilize synaptic reorganization patterns in both hemispheres, to compete with the capacity for experiences of the paretic side to do so. However, the competitive edge of the non-paretic side can be countered by overlapping experiences of the paretic hand, and might even be shifted in a cooperative direction with skilfully coordinated bimanual experience. Advances in the basic understanding of learning-related synaptic competition are helping to inform the basis of experience-dependent variations in stroke outcome., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

A vast body of research suggests that the primary motor cortex is involved in motor imagery. This raises the issue of inhibition: how is it possible for motor imagery not to lead to motor execution? Bach et al. (Psychol Res Psychol Forschung. 10.1007/s00426-022-01773-w, 2022, this issue) suggest that the motor execution threshold may be "upregulated" during motor imagery to prevent execution. Alternatively, it has been proposed that, in parallel to excitatory mechanisms, inhibitory mechanisms may be actively suppressing motor output during motor imagery. These theories are verbal in nature, with well-known limitations. Here, we describe a toy-model of the inhibitory mechanisms thought to be at play during motor imagery to start disentangling predictions from competing hypotheses., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Inhibition is a key cognitive control mechanism humans use to enable goal-directed behavior. When rapidly exerted, inhibitory control has broad, nonselective motor effects, typically demonstrated using corticospinal excitability measurements (CSE) elicited by transcranial magnetic stimulation (TMS). For example, during rapid action-stopping, CSE is suppressed at both stopped and task-unrelated muscles. While such TMS-based CSE measurements have provided crucial insights into the fronto-basal ganglia circuitry underlying inhibitory control, they have several downsides. TMS is contraindicated in many populations (e.g., epilepsy or deep-brain stimulation patients), has limited temporal resolution, produces distracting auditory and haptic stimulation, is difficult to combine with other imaging methods, and necessitates expensive, immobile equipment. Here, we attempted to measure the nonselective motor effects of inhibitory control using a method unaffected by these shortcomings. Thirty male and female human participants exerted isometric force on a high-precision handheld force transducer while performing a foot-response stop-signal task. Indeed, when foot movements were successfully stopped, force output at the task-irrelevant hand was suppressed as well. Moreover, this nonselective reduction of isometric force was highly correlated with stop-signal performance and showed frequency dynamics similar to established inhibitory signatures typically found in neural and muscle recordings. Together, these findings demonstrate that isometric force recordings can reliably capture the nonselective effects of motor inhibition, opening the door to many applications that are hard or impossible to realize with TMS., (© 2023. The Psychonomic Society, Inc.)

This study investigated the effects of poi (a weight on the end of a cord which is swung in circular patterns around the body) compared with Tai Chi on physical and cognitive function in healthy older adults. A total of 79 participants (60-86 years) were randomly allocated to the poi or Tai Chi group. Physical and cognitive function was measured 1 month before, immediately before, immediately after, and 1 month after the intervention (two lessons a week, for 4 weeks). Immediately postintervention, both groups improved postural stability, upper limb strength, and simple attention. Tai Chi also improved systolic blood pressure. One-month postintervention, compared with immediately postintervention, both groups improved upper limb strength, upper limb range of motion, and memory. Poi also improved systolic blood pressure. Therefore, poi seems to be as effective as Tai Chi for improving physical and cognitive function in healthy older adults.

The Re-Link Trainer (RLT) is a modified walking frame with a linkage system designed to apply a non-individualized kinematic constraint to normalize gait trajectory of the left limb. The premise behind the RLT is that a user's lower limb is constrained into a physiologically normal gait pattern, ideally generating symmetry across gait cycle parameters and kinematics. This pilot study investigated adaptations in the natural gait pattern of healthy adults when using the RLT compared to normal overground walking. Bilateral lower limb kinematic and electromyography data were collected while participants walked overground at a self-selected speed, followed by walking in the RLT. A series of 2-way analyses of variance examined between-limb and between-condition differences. Peak hip extension and knee flexion were reduced bilaterally when walking in the RLT. Left peak hip extension occurred earlier in the gait cycle when using the RLT, but later for the right limb. Peak hip flexion was significantly increased and occurred earlier for the constrained limb, while peak plantarflexion was significantly reduced. Peak knee flexion and plantarflexion in the right limb occurred later when using the RLT. Significant bilateral reductions in peak electromyography amplitude were evident when walking in the RLT, along with a significant shift in when peak muscle activity was occurring. These findings suggest that the RLT does impose a significant constraint, but generates asymmetries in lower limb kinematics and muscle activity patterns. The large interindividual variation suggests users may utilize differing motor strategies to adapt their gait pattern to the imposed constraint., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Stroke is a leading cause of adult disability that results in motor deficits and reduced independence. Regaining independence relies on motor recovery, particularly regaining function of the hand and arm. This review presents evidence from human studies that have used transcranial magnetic stimulation (TMS) to identify neurophysiological mechanisms underlying upper limb motor recovery early after stroke. TMS studies undertaken at the subacute stage after stroke have identified several neurophysiological factors that can drive motor impairment, including membrane excitability, the recruitment of corticomotor neurons, and glutamatergic and GABAergic neurotransmission. However, the inherent variability and subsequent poor reliability of measures derived from motor evoked potentials (MEPs) limit the use of TMS for prognosis at the individual patient level. Currently, prediction tools that provide the most accurate information about upper limb motor outcomes for individual patients early after stroke combine clinical measures with a simple neurophysiological biomarker based on MEP presence or absence, i.e. MEP status. Here, we propose a new compositional framework to examine MEPs across several upper limb muscles within a threshold matrix. The matrix can provide a more comprehensive view of corticomotor function and recovery after stroke by quantifying the evolution of subthreshold and suprathreshold MEPs through compositional analyses. Our contention is that subthreshold responses might be the most sensitive to reduced output of corticomotor neurons, desynchronized firing of the remaining neurons, and myelination processes that occur early after stroke. Quantifying subthreshold responses might provide new insights into post-stroke neurophysiology and improve the accuracy of prediction of upper limb motor outcomes., (© 2024 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Stroke is one of the leading causes of adult disability affecting millions of people worldwide. Post-stroke cognitive and motor impairments diminish quality of life and functional independence. There is an increased risk of having a second stroke and developing secondary conditions with long-term social and economic impacts. With increasing number of stroke incidents, shortage of medical professionals and limited budgets, health services are struggling to provide a care that can break the vicious cycle of stroke. Effective post-stroke recovery hinges on holistic, integrative and personalized care starting from improved diagnosis and treatment in clinics to continuous rehabilitation and support in the community. To improve stroke care pathways, there have been growing efforts in discovering biomarkers that can provide valuable insights into the neural, physiological and biomechanical consequences of stroke and how patients respond to new interventions. In this review paper, we aim to summarize recent biomarker discovery research focusing on three modalities (brain imaging, blood sampling and gait assessments), look at some established and forthcoming biomarkers, and discuss their usefulness and complementarity within the context of comprehensive stroke care. We also emphasize the importance of biomarker guided personalized interventions to enhance stroke treatment and post-stroke recovery., (© 2024 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Walking function post-stroke is characterized by asymmetries in gait cycle parameters and joint kinematics. The Re-Link Trainer is designed to provide kinematic constraint to the paretic lower limb, to guide a physiologically normal and symmetrical gait pattern. The purpose of this pilot study was to assess the immediate influence of the Re-Link Trainer on measures of gait symmetry in healthy adults. Participants demonstrated a significantly lower cadence and a 62% reduction in walking speed in the Re-Link Trainer compared to normal walking. The step length ratio had a significant increase from 1.0 during normal walking to 2.5 when walking in the Re-Link Trainer. The results from this pilot study suggest in its current iteration the Re-Link Trainer imposes an asymmetrical constraint on lower limb kinematics.

Background: Previous research has shown that measuring the size and content of patients' drawings of their illness can reveal their perceptions and predict recovery. This study aimed to assess the usefulness of analyzing kinematic features of drawings., Methods: A pilot observational study was conducted with 15 patients who had been hospitalized with a stroke 8 to 11 months previously. They were asked to draw a picture of what they thought had happened to their brain and describe the drawing using an electronic inking pen and digitizing tablet. Analysis of kinematic data (time to draw/write, drawing/writing speed, and pen pressure) was conducted using MovAlyzeR® software. Evaluations of physical functioning, quality of life, illness perceptions, and emotional well-being were administered, and correlations with kinematic measures assessed., Results: Stronger pen pressure was associated with perceptions of greater control over the stroke. Faster drawing was correlated with greater worry about a recurrent stroke and the perception that the effects of the stroke would last longer. Needing more time to write was associated with perceptions of fewer consequences of the stroke. No associations between kinematic measures and indicators of stroke severity, physical, or emotional well-being were shown., Conclusions: Kinematic measures of stroke patients' drawings of their brain and comments were associated with illness perceptions and not measures of physical or emotional health status. The addition of kinematic analysis may add further utility to the assessment of patients' drawings of their illness. More studies need to be performed with larger sample sizes and other patient groups.

Together, we grow our profession of occupational therapy as we engage in understanding and addressing the issues that challenge the people we work with. In this Sylvia Docker Lecture, I will share the collective journeys of myself and other occupational therapists and health professionals who have undertaken (or are currently undertaking) their PhDs and are actively involved in research, to address these challenges. Together, we will explore three themes: understanding the WHY that ignites one's passion; living the journey-the EXPERIENCE; and making a difference-the IMPACT. Stories will be told through the lived experience of those engaged in research as currently enrolled PhD students, emerging researchers, and experienced researchers. These stories will capture the lived experience across individuals, and at different times in the research journey. Stories are summarised and captured using natural language processing. Topics are identified, concept maps visualised, and outputs interpreted in context of related theoretical models. Key topics identified include: the clinical and personal motivators that have ignited the passion in individuals; the value of connecting with others and growing networks; and how one's research has made a difference. The impact of discoveries and outcomes are highlighted, together with the importance of people and networks. Analysis of connections and synthesis over time revealed frequent and strong connections across themes, concepts and topics; with synthesising concepts of passion, networks, knowledge translation, opportunities, supervision and communication emerging and being shaped over time. These collective journeys provide inspiration and pathways to creative careers that have future potential in the growth of the profession of occupational therapy. It is recommended that each occupational therapist take the time to reflect on the 'why' that ignites your passion, your journey and how you can make a difference!, (© 2024 The Author. Australian Occupational Therapy Journal published by John Wiley & Sons Australia, Ltd on behalf of Occupational Therapy Australia.)

Tactile imagery remains a relatively understudied phenomenon of mental imagery research. However, this technique holds promise as an effective tool for sensorimotor rehabilitation following stroke and spinal cord injuries alongside motor imagery. In this study, conducted with 22 healthy volunteers, the authors investigated the source localization of μ-rhythm event-related desynchronization (ERD) using multichannel electroencephalogram recordings and subsequent inverse problem solution with the sLORETA. All participants exhibited ERD during tactile imagery task and under vibrotactile stimulation. It was demonstrated that μ-rhythm ERD during both vibrotactile stimulation and tactile imagery was localized in the sensorimotor areas of the contralateral hemisphere. Within the source space, ERD in the postcentral gyrus was significantly stronger compared to the precentral gyrus. These findings indicate that tactile imagery, akin to the perception of real tactile stimuli, leads to prominent activation of sensorimotor cortical areas, consistent with the general understanding of the shared neural substrate during mental imagery and perception. [ABSTRACT FROM AUTHOR]

The Stop Signal Task (SST) has been the benchmark for studying the behavioral and physiological basis of movement generation and inhibition. In our study, we extended the scope beyond physiological findings related to muscle activity, focusing our analysis on the initial biomechanical state of the effector. By incorporating a force sensitive resistor (FSR), we continuously monitored the force applied by the effector (here, the index finger) during a button release version of the SST. This modified task design allowed us to examine both the baseline force before the relevant Go signal was presented and during the covert state of movement preparation. Notably, variations in force over time in response to the Go signal revealed differences across trials where movement was either generated or successfully inhibited, depending on the amount of force during the baseline period. Specifically, higher baseline force was associated with a delayed movement generation, which, simultaneously slowed down the force release, facilitating successful inhibition when requested. Our results highlight the influence of biomechanical variables in movement control, which should be accounted for by the models developed for investigating the physiology of this ability. [ABSTRACT FROM AUTHOR]

Alzheimer disease (AD) remains a significant global health concern. The progression from preclinical stages to overt dementia has become a crucial point of interest for researchers. This paper reviews the potential of neurophysiological biomarkers in predicting AD progression, based on a systematic literature search following PRISMA guidelines, including 55 studies. EEG-based techniques have been predominantly employed, whereas TMS studies are less common. Among the investigated neurophysiological measures, spectral power measurements and event-related potentials-based measures, including P300 and N200 latencies, have emerged as the most consistent and reliable biomarkers for predicting the likelihood of conversion to AD. In addition, TMS-based indices of cortical excitability and synaptic plasticity have also shown potential in assessing the risk of conversion to AD. However, concerns persist regarding the methodological discrepancies among studies, the accuracy of these neurophysiological measures in comparison to established AD biomarkers, and their immediate clinical applicability. Further research is needed to validate the predictive capabilities of EEG and TMS measures. Advancements in this area could lead to cost-effective, reliable biomarkers, enhancing diagnostic processes and deepening our understanding of AD pathophysiology. [ABSTRACT FROM AUTHOR]

Transcranial magnetic stimulation (TMS) methods have become exciting techniques for altering brain activity and improving synaptic plasticity, earning recognition as valuable non-medicine treatments for a wide range of neurological disorders. Among these methods, repetitive TMS (rTMS) and theta-burst stimulation (TBS) show significant promise in improving outcomes for adults with complex neurological and neurodegenerative conditions, such as Alzheimer's disease, stroke, Parkinson's disease, etc. However, optimizing their effects remains a challenge due to variability in how patients respond and a limited understanding of how these techniques interact with crucial neurotransmitter systems. This narrative review explores the mechanisms of rTMS and TBS, which enhance neuroplasticity and functional improvement. We specifically focus on their effects on GABAergic and glutamatergic pathways and how they interact with key receptors like N-Methyl-D-Aspartate (NMDA) and AMPA receptors, which play essential roles in processes like long-term potentiation (LTP) and long-term depression (LTD). Additionally, we investigate how rTMS and TBS impact neuroplasticity and functional connectivity, particularly concerning brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase receptor type B (TrkB). Here, we highlight the significant potential of this research to expand our understanding of neuroplasticity and better treatment outcomes for patients. Through clarifying the neurobiology mechanisms behind rTMS and TBS with neuroimaging findings, we aim to develop more effective, personalized treatment plans that effectively address the challenges posed by neurological disorders and ultimately enhance the quality of neurorehabilitation services and provide future directions for patients' care. [ABSTRACT FROM AUTHOR]

Structural disconnectome analyses have provided valuable insights into how a stroke lesion results in widespread network disturbances and how these relate to deficits, recovery patterns, and outcomes. Previous analyses have primarily focused on patients with relatively mild to moderate deficits. However, outcomes vary among survivors of severe strokes, and the mechanisms of recovery remain poorly understood. This study assesses the association between lesion‐induced network disconnection and outcome after severe stroke. Thirty‐eight ischaemic stroke patients underwent MRI brain imaging early after stroke and longitudinal clinical follow‐up. Lesion information was integrated with normative connectome data to infer individual disconnectome profiles on a localized regional and region‐to‐region pathway level. Ordinal logistic regressions were computed to link disconnectome information to the modified Rankin Scale after 3–6 months. Disconnections of ipsilesional frontal, parietal, and temporal cortical brain areas were significantly associated with a worse motor outcome after a severe stroke, adjusted for the initial deficit, lesion volume, and age. The analysis of the underlying pathways mediating this association revealed location‐specific results: For frontal, prefrontal, and temporal brain areas, the association was primarily driven by relatively sparse intrahemispheric disconnections. In contrast, the ipsilesional primary motor cortex, the dorsal premotor cortex, and various parietal brain regions showed a remarkable involvement of either frontoparietal intrahemispheric or additionally interhemispheric disconnections. These results indicate that localized disconnection of multiple regions embedded in the structural frontoparietal network correlates with worse outcomes after severe stroke. Specifically, primary motor and parietal cortices might gain particular importance as they structurally link frontoparietal networks of both hemispheres. These data shed novel light on the significance of distinct brain networks for recovery after a severe stroke. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to identify the neural pattern activation during mirror therapy (MT) and explore any cortical reorganization and reducing asymmetry of hemispheric activity for upper limb rehabilitation in post-stroke patients. Methods: A box containing a mirror was placed between the arms of the patients to create the illusion of normal motion in the affected limb by reflecting the image of the unaffected limb in motion. We measured the cerebral hemodynamic response using near-infrared spectroscopy (NIRS). We enrolled ten right-handed stroke patients. They observed healthy hand movements in the mirror (MT condition) while performing various tasks (MT condition), and then repeated the same tasks with the mirror covered (N-MT condition). Results: Significant activation of some brain areas was observed in the right and left hemiparesis groups for the MT condition, while lower levels of activation were observed for the N-MT condition. The results showed significant differences in hemodynamic response based on oxygenated (HbO) concentrations between MT and N-MT conditions across all tasks in sensorimotor areas. These neural circuits were activated despite the motor areas being affected by the brain injury, indicating that the reflection of movement in the mirror helped to activate them. Conclusions: These results suggest that MT promotes cortical activations of sensory motor areas in affected and non-affected brain sides in subacute post-stroke patients, and it encourages the use of these tools in clinical practice. [ABSTRACT FROM AUTHOR]

Disruptions in the brain's connections to the hands resulting from a cervical spinal cord injury (cSCI) can lead to severe and persistent functional impairments. The integrity of these connections is an important predictor of upper extremity recovery in stroke and may similarly act as a biomarker in cSCI. In this perspective article, we review recent findings from a large cohort of individuals with cSCI, demonstrating the predictive value of corticospinal tract (CST) integrity in cSCI—CST sparing. This research underscores that, akin to stroke, the integrity of brain-to-hand connections is crucial for predicting upper extremity recovery following cSCI. We address the limitations of commonly used metrics, such as sacral sparing and the concept of central cord syndrome. Furthermore, we offer insights on emerging metrics, such as tissue bridges, emphasizing their potential in assessing the integrity of brain connections to the spinal cord. [ABSTRACT FROM AUTHOR]

Introduction: Several clinical studies have demonstrated that brain-computer interfaces (BCIs) controlled functional electrical stimulation (FES) facilitate neurological recovery in patients with stroke. This review aims to evaluate the effectiveness of BCI-FES training on upper limb functional recovery in stroke patients. Methods: PubMed, Embase, Cochrane Library, Science Direct and Web of Science were systematically searched from inception to October 2023. Randomized controlled trials (RCTs) employing BCI-FES training were included. The methodological quality of the RCTs was assessed using the PEDro scale. Meta-analysis was conducted using RevMan 5.4.1 and STATA 18. Results: The meta-analysis comprised 290 patients from 10 RCTs. Results showed a moderate effect size in upper limb function recovery through BCI-FES training (SMD=0.50, 95% CI: 0.26-0.73, I² =0%, p <0.0001). Subgroup analysis revealed that BCI-FES training significantly enhanced upper limb motor function in BCI-FES vs. FES group (SMD=0.37, 95% CI: 0.00-0.74, I² =21%, p =0.05), and the BCI-FES+CR vs. CR group (SMD=0.61, 95% CI: 0.28-0.95, I² =0%, p =0.0003). Moreover, BCI-FES training demonstrated effectiveness in both subacute (SMD=0.56, 95% CI: 0.25-0.87, I² =0%, p =0.0004) and chronic groups (SMD=0.42, 95% CI: 0.05-0.78, I² =45%, p =0.02). Subgroup analysis showed that both adjusting (SMD=0.55, 95% CI: 0.24- 0.87, I² =0%, p =0.0006) and fixing (SMD=0.43, 95% CI: 0.07-0.78, I² =46%, p =0.02). BCI thresholds before training significantly improved motor function in stroke patients. Both motor imagery (MI) (SMD=0.41 95% CI: 0.12-0.71, I² =13%, p =0.006) and action observation (AO) (SMD=0.73, 95% CI: 0.26-1.20, I² =0%, p =0.002) as mental tasks significantly improved upper limb function in stroke patients. Discussion: BCI-FES has significant immediate effects on upper limb function in subacute and chronic stroke patients, but evidence for its long-term impact remains limited. Using AO as the mental task may be a more effective BCI-FES training strategy. [ABSTRACT FROM AUTHOR]

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