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Gut microbiota perturbation and motor dysfunction have been reported in steatosis patients. Rats with mild liver damage (MLD) show motor dysfunction mediated by neuroinflammation and altered GABAergic neurotransmission in the cerebellum. The extracellular vesicles (EV) from mesenchymal stem cells (MSC) have emerged as a promising therapeutic proxy whose molecular basis relies partly upon TGFß action. This study aimed to assess if MSC-EVs improve motor dysfunction in rats with mild liver damage and analyze underlying mechanisms, including the role of TGFß, cerebellar neuroinflammation and gut microbiota. MLD in rats was induced by carbon tetrachloride administration and EVs from normal (C-EVs) or TGFß-siRNA treated MSCs (T-EV) were injected. Motor coordination, locomotor gait, neuroinflammation and TNF-α-activated pathways modulating GABAergic neurotransmission in the cerebellum, microbiota composition in feces and microbial-derived metabolites in plasma were analyzed. C-EVs reduced glial and TNFα-P2X4-BDNF-TrkB pathway activation restoring GABAergic neurotransmission in the cerebellum and improving motor coordination and all the altered gait parameters. T-EVs also improved motor coordination and some gait parameters, but the mechanisms involved differed from those of C-EVs. MLD rats showed increased content of some Bacteroides species in feces, correlating with decreased kynurenine aside from motor alterations. These alterations were all normalized by C-EVs, whereas T-EVs only restored kynurenine levels. Our results support the value of MSC-EVs on improving motor dysfunction in MLD and unveil a possible mechanism by which altered microbiota may contribute to neuroinflammation and motor impairment. Some of the underlying mechanisms are TGFß-dependent.

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Background: MED13L-related disorder is associated with intellectual disability, motor delay, and speech deficits. Previous studies have focused on broad clinical descriptions of individuals, but limited information regarding specific speech diagnoses and results of direct testing has been published to date. We conducted deep phenotyping to characterize the speech, language, motor, cognitive, and adaptive phenotypes of individuals with MED13L-related disorder. Methods: In this cross-sectional study, we administered standardized articulation, language, motor, and cognitive testing to 17 children and adolescents (mean age 9y 9m; SD 4y 5m; range 4y 2m to 19y 7m). In-person testing was supplemented with broad developmental, medical, and behavioral information collected virtually from a cohort of 67 individuals. Results: All individuals who completed in-person articulation testing met diagnostic criteria for speech apraxia, dysarthria, or both. Language impairment was present in all of the in-person cohort and almost all (97%) of the virtual cohort. Those who were able to complete motor testing demonstrated significant deficits in visual motor integration (mean 57.08, SD 9.26). Full scale IQs fell in the borderline to intellectual disability range, consistent with reported cognitive impairment in 97% of the virtual cohort. Notable medical features included hypotonia (83%), vision problems (72%), recurrent otitis media (58%), gastrointestinal problems (57%), and seizures (31%). Conclusions: MED13L-related disorder is characterized by a high rate of motor speech disorders that occur in the context of globally impaired motor, language, and cognitive skills. Children would benefit from intensive, individualized speech therapy and the early adoption of augmentative communication strategies.

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BACKGROUND: Patient-rated motor symptoms (PRMS) and clinician-rated motor symptoms (CRMS) often differ in Parkinson's disease (PD). OBJECTIVE: Our goal was to investigate the determinants and clinical implications of PRMS compared with CRMS in PD. METHODS: This retrospective, observational cohort study analyzed the cross-sectional associations and longitudinal impacts of PRMS as assessed by the Movement Disorders Society-sponsored Unified PD Rating Scale (MDS-UPDRS) part 2, while controlling for CRMS measured by MDS-UPDRS part 3. Longitudinal analyses used Cox proportional hazards models and multiple linear mixed-effects random intercepts/slope models, adjusting for many clinical predictors. We conducted propensity score matching (PSM) to reinforce our analyses' robustness and surface-based morphometry to investigate neural correlates. RESULTS: We enrolled 442 patients with early-stage PD. At baseline, regardless of CRMS, PRMS were associated with the severity of postural instability and gait disturbance (PIGD). Notably, PRMS independently and more accurately predicted faster long-term deterioration in motor function than CRMS (Hoehn and Yahr 4, adjusted hazard ratio per +1 point = 1.19 [95% confidence intervals, 1.08-1.32]), particularly in PIGD (PIGD subscore, ß-interaction = 0.052 [95% confidence intervals, 0.018-0.086]). PSM confirmed these findings' robustness. Surface-based morphometry suggested that enhanced sensory processing was distinctively associated with PRMS. CONCLUSIONS: In early-stage PD, PRMS weighed different aspects of symptoms and more effectively predicted motor deterioration compared to CRMS, with distinctive brain structural characteristics. The superior sensitivity of PRMS to subtle declines in drug-refractory symptoms like PIGD likely underlie our results, highlighting the importance of understanding the differential clinical implications of PRMS to prevent long-term motor deterioration. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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Objectives: This review quantitatively evaluates the effectiveness of gross-motor-based interventions in children with developmental coordination disorder (DCD), examining treatment aspects such as group interventions, therapy duration, and frequency. Methods: A systematic literature review, spanning January 2010 to December 2022, identified 11 relevant articles involving 492 children. Results: Positive outcomes were observed, with a moderate to large overall effect size (Cohen's d) indicating significant improvements in motor function through strategies emphasizing activity, bodily function, games, and small group events. Notably, interventions targeting complex motor skills were crucial for enhancing preparedness and activity engagement, improving fitness, and preventing obesity in children with DCD. Conclusions: The review underscores the effectiveness of activity-oriented and body-function-focused therapies in enhancing motor skills and functioning, emphasizing the need for interventions aligned with real-world activities. Future research should explore the long-term effects and retention of motor improvements, offering valuable insights for designing targeted interventions to promote overall well-being in children with DCD.

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Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative condition leading to progressive muscle weakness, atrophy, and ultimately death. Traditional ALS clinical evaluations often depend on subjective metrics, making accurate disease detection and monitoring disease trajectory challenging. To address these limitations, we developed the nQiALS toolkit, a machine learning-powered system that leverages smartphone typing dynamics to detect and track motor impairment in people with ALS. The study included 63 ALS patients and 30 age- and sex-matched healthy controls. We introduce the three core components of this toolkit: the nQiALS-Detection, which differentiated ALS from healthy typing patterns with an AUC of 0.89; the nQiALS-Progression, which separated slow and fast progression at specific thresholds with AUCs ranging between 0.65 and 0.8; and the nQiALS-Fine Motor, which identified subtle progression in fine motor dysfunction, suggesting earlier prediction than the state-of-the-art assessment. Together, these tools represent an innovative approach to ALS assessment, offering a complementary, objective metric to traditional clinical methods and which may reshape our understanding and monitoring of ALS progression.

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Stroke is recognized as a network communication disorder. Advances in neuroimaging technologies have enhanced our comprehension of dynamic cerebral alterations. However, different levels of motor function impairment after stroke may have different patterns of brain reorganization. Abnormal and adaptive patterns of brain activity in mild-to-moderate motor function impairments after stroke remain still underexplored. We aim to identify dynamic patterns of network remodeling in stroke patients with mild-to-moderate impairment of motor function. fMRI data were obtained from 30 stroke patients and 31 healthy controls to establish a spatiotemporal multilayer modularity model. Then, graph-theoretic measures, including modularity, flexibility, cohesion, and disjointedness, were calculated to quantify dynamic reconfiguration. Our findings reveal that the post-stroke brain exhibited higher modular organization, as well as heightened disjointedness, compared to HCs. Moreover, analyzing from the network level, we found increased disjointedness and flexibility in the Default mode network (DMN), indicating that brain regions tend to switch more frequently and independently between communities and the dynamic changes were mainly driven by DMN. Notably, modified functional dynamics positively correlated with motor performance in patients with mild-to-moderate motor impairment. Collectively, our research uncovered patterns of dynamic community reconstruction in multilayer networks following stroke. Our findings may offer new insights into the complex reorganization of neural function in post-stroke brain.

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A prevalent long-term medical condition in children that is rarely understood and acknowledged in educational contexts is developmental coordination disorder (DCD), which is one of the most prevalent conditions in school-aged children. Mild-to-severe abnormalities in muscle tone, posture, movement, and the learning of motor skills are associated with motor disorders. Early detection of developmental abnormalities in children is crucial as delayed motor milestones during infancy might indicate a delay in both physical and neurological development. To overcome the current condition of motor impairment, obstructing their risk factors is important to prevent the development of disability, which is already determined in the prenatal and perinatal period. Concerning the relationship with gestational age, the majority of the studies reported a relationship between DCD and preterm children. However, the entire range of gestational age, including post-term birth, has not been studied. The risk of developmental consequences such as cognitive impairments, major mental diseases, attention-deficit/hyperactivity disorder, autism spectrum disorder, and other behavioral and emotional problems increases in post-term birth, according to prior studies. Thus, this review aims to provide an overview of information linking post-term birth to children's motor impairment, with a focus on DCD. A thorough systemic review was conducted on online databases, and only a few studies were found on the association with post-term children. Insufficient evidence made it necessary to examine more post-term cohorts in adolescence to fully determine the long-term health concerns and develop therapies to mitigate the detrimental effects of post-term deliveries.

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Background: Parkinson's disease (PD) affects more than 6 million people worldwide. Along with motor impairments, patients and animal models exhibiting PD symptoms also experience cognitive impairment, fatigue, anxiety, and depression. Currently, there are no drugs available for PD that alter the progression of the disease. A body of evidence suggests that increased GABA levels contribute to the reduced expression of tyrosine hydroxylase (TH) and accompanying behavioral deficits. TH expression may be restored by blocking GABAA receptors. We hypothesized that golexanolone (GR3027), a well-tolerated GABAA receptor-modulating steroid antagonist (GAMSA), may improve Parkinson's symptoms in a rat model of PD. Objectives: The aims of this study were to assess whether golexanolone can ameliorate motor and non-motor symptoms in a rat model of PD and to identify some underlying mechanisms. Methods: We used the unilateral 6-OHDA rat model of PD. The golexanolone treatment started 4 weeks after surgery. Motor symptoms were assessed using Motorater and CatWalk tests. We also analyzed fatigue (using a treadmill test), anhedonia (via the sucrose preference test), anxiety (with an open field test), and short-term memory (using a Y maze). Glial activation and key proteins involved in PD pathogenesis were analyzed using immunohistochemistry and Western blot. Results: Rats with PD showed motor incoordination and impaired locomotor gait, increased fatigue, anxiety, depression, and impaired short-term memory. Golexanolone treatment led to improvements in motor incoordination, certain aspects of locomotor gait, fatigue, anxiety, depression, and short-term memory. Notably, golexanolone reduced the activation of microglia and astrocytes, mitigated TH loss at 5 weeks after surgery, and prevented the increase of α-synuclein levels at 10 weeks. Conclusions: Golexanolone may be useful in improving both motor and non-motor symptoms that adversely affect the quality of life in PD patients, such as anxiety, depression, fatigue, motor coordination, locomotor gait, and certain cognitive alterations.

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BACKGROUND: Upper limb motor impairment commonly occurs after stroke, impairing quality of life. Brain network reorganization likely differs between subgroups with differing impairment severity. This study explored differences in functional connectivity (FC) and corticospinal tract (CST) integrity between patients with mild/moderate versus severe hemiplegia poststroke to clarify the neural correlates underlying motor deficits. METHOD: Sixty chronic stroke patients with upper limb motor impairment were categorized into mild/moderate and severe groups based on Fugl-Meyer scores. Resting-state FC was assessed using functional near-infrared spectroscopy (fNIRS) to compare connectivity patterns between groups across motor regions. CST integrity was evaluated by inducing motor evoked potentials (MEP) via transcranial magnetic stimulation. RESULTS: Compared to the mild/moderate group, the severe group exhibited heightened premotor cortex-primary motor cortex (PMC-M1) connectivity (t = 4.56, p < 0.01). Absence of MEP was also more frequent in the severe group (χ2 = 12.31, p = 0.01). Bayesian models effectively distinguished subgroups and identified the PMC-M1 connection as highly contributory (accuracy = 91.30%, area under the receiver operating characteristic curve [AUC] = 0.86). CONCLUSION: Distinct patterns of connectivity and corticospinal integrity exist between stroke subgroups with differing impairments. Strengthened connectivity potentially indicates recruitment of additional motor resources to compensate for damage. These findings elucidate the neural correlates underlying motor deficits poststroke and could guide personalized, network-based therapies targeting predictive biomarkers to improve rehabilitation outcomes.

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BACKGROUND: Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. METHODS: Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0-53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0-70.0] years, 55.7% female) completed in-person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form-36 physical/mental summary scores, social attainment). RESULTS: Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%-29.4%) than controls (2.9%, CI 1.4-4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m2 versus none (OR 4.38, CI 1.06-18.08) and etoposide exposure >2036 mg/m2 versus none (OR 12.61, CI 2.19-72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01-1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68-11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10-0.84, Sensory: OR 0.35, CI 0.13-0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22-5.72). CONCLUSIONS: In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL.

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Motor delays in children with autism spectrum disorder (ASD) are being increasingly recognized using a brief screening tool, called the Developmental Coordination Disorder-Questionnaire (DCD-Q). Further validation of these motor delays using a more robust normed, developmental measure is clearly warranted. In this analysis, a nationally representative sample from the SPARK study was used wherein parents completed the DCD-Q and a more widely used developmental/adaptive functioning measure, called the Vineland Adaptive Behavior Scales (VABS); which comprises of various developmental domains including the motor domain (N = 2,644 completed the DCD-Q and VABS). Eighty two percent children with ASD had a motor delay based on their DCD-Q scores whereas 77% children with ASD had a motor delay based on their VABS motor domain scores. Approximately 70% children with ASD had concurrent motor delay on the DCD-Q and the VABS (i.e., positive predictive value of DCD-Q). Furthermore, there was 81.2% accuracy in reporting a risk/no risk of motor delay across both measures. Overall, these statistics align with the recent reports on proportions of children with ASD having motor delays. Parents of ~70% children with ASD are reporting motor delays that are corroborated across two different motor measures. This not only validates the motor delays reported based on the DCD-Q but also indicates the need for concurrent motor screening using both DCD-Q and VABS for better detection of motor delays in children with ASD. Only 10%-32% of the current SPARK sample received any physical or recreational therapies. This mismatch between presence of motor delays and the lack of access to motor services highlights the need for more motor intervention referrals for children with ASD.

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Frailty is a geriatric, multi-dimensional syndrome that reflects multisystem physiological change and is a transversal measure of reduced resilience to negative events. It is characterized by weakness, frequent falls, cognitive decline, increased hospitalization and dead and represents a risk factor for the development of Alzheimer's disease (AD). The fact that frailty is recognized as a reversible condition encourages the identification of earlier biomarkers to timely predict and prevent its occurrence. SAMP8 (Senescence-Accelerated Mouse Prone-8) mice represent the most appropriate preclinical model to this aim and were used in this study to carry transcriptional and metabolic analyses in the brain and plasma, respectively, upon a characterization at cognitive, motor, structural, and neuropathological level at 2.5, 6, and 9 months of age. At 2.5 months, SAMP8 mice started displaying memory deficits, muscle weakness, and motor impairment. Functional alterations were associated with a neurodevelopmental deficiency associated with reduced neuronal density and glial cell loss. Through transcriptomics, we identified specific genetic signatures well distinguishing SAMP8 mice at 6 months, whereas plasma metabolomics allowed to segregate SAMP8 mice from SAMR1 already at 2.5 months of age by detecting constitutively lower levels of acylcarnitines and lipids in SAMP8 at all ages investigated correlating with functional deficits and neuropathological signs. Our findings suggest that specific genetic alterations at central level, as well as metabolomic changes in plasma, might allow to early assess a frail condition leading to dementia development, which paves the foundation for future investigation in a clinical setting.

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Zika virus (ZIKV) is a neurotropic Orthoflavivirus that causes a myriad of neurological manifestations in newborns exposed in uterus. Despite the devastating consequences of ZIKV on the developing brain, strategies to prevent or treat the consequences of viral infection are not yet available. We previously showed that short-term treatment with the TNF-α neutralizing monoclonal antibody. Infliximab could prevent seizures at acute and chronic stages of ZIKV infection, but had no impact on long-term cognitive and motor dysfunction. Due to the central role of inflammation in ZIKV-neuropathology, we hypothesized that prolonged treatment with the anti-TNF-α monoclonal antibody Infliximab could provide complete rescue of long-term behavioral deficits associated with neonatal ZIKV infection in mice. Here, neonatal (post-natal day 3) Swiss mice were submitted to subcutaneous (s.c.) injection of 106 PFU of ZIKV or mock medium and were then treated with Infliximab (20 µg/day) or sterile saline intraperitoneally (i.p.), for 40 days starting on the day of infection, and behavioral assessment started at 60 days post-infection (dpi). Infliximab prevented ZIKV-induced cognitive and motor impairments in mice. In addition, microgliosis and cell death found in mice following ZIKV infection were partially reversed by TNF-α blockage. Altogether, these results suggest that TNF-α-mediated inflammation is central for late ZIKV-induced behavioral deficits and cell death and strategies targeting this cytokine may be promising approaches to treat subjects exposed to the virus during development.

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Predictive processing, a crucial aspect of human cognition, is also relevant for language comprehension. In everyday situations, we exploit various sources of information to anticipate and therefore facilitate processing of upcoming linguistic input. In the literature, there are a variety of models that aim at accounting for such ability. One group of models propose a strict relationship between prediction and language production mechanisms. In this review, we first introduce very briefly the concept of predictive processing during language comprehension. Secondly, we focus on models that attribute a prominent role to language production and sensorimotor processing in language prediction ("prediction-by-production" models). Contextually, we provide a summary of studies that investigated the role of speech production and auditory perception on language comprehension/prediction tasks in healthy, typical participants. Then, we provide an overview of the limited existing literature on specific atypical/clinical populations that may represent suitable testing ground for such models-i.e., populations with impaired speech production and auditory perception mechanisms. Ultimately, we suggest a more widely and in-depth testing of prediction-by-production accounts, and the involvement of atypical populations both for model testing and as targets for possible novel speech/language treatment approaches.

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Rotenone (RTN) induces neurotoxicity and motor dysfunction in rats, mirroring the pathophysiological traits of Parkinson's disease (PD), including striatal oxidative stress, mitochondrial dysfunction, and changes in neural structure. This makes RTN a valuable model for PD research. Berberine (BBR), an isoquinoline alkaloid recognized for its antioxidative, anti-inflammatory, and neuroprotective properties, was evaluated for its ability to counteract RTN-induced impairments. Rats received subcutaneous RTN at 0.5 mg/kg for 21 days, resulting in weight loss and significant motor deficits assessed through open-field, bar catalepsy, beam-crossing, rotarod, and grip strength tests. BBR, administered orally at 30 or 100 mg/kg doses, one hour prior to RTN exposure for the same duration, effectively mitigated many of the RTN-induced motor impairments. Furthermore, BBR treatment reduced RTN-induced nitric oxide (NO) and lipid peroxidation (LPO) levels, bolstered antioxidative capacity, enhanced mitochondrial enzyme activities (e.g., succinate dehydrogenase (SDH), ATPase, and the electron transport chain (ETC)), and diminished striatal neuroinflammation and apoptosis markers. Notably, the co-administration of trigonelline (TGN), an inhibitor of the nuclear factor erythroid-2-related factor 2 (Nrf2) pathway, significantly attenuated BBR's protective effects, indicating that BBR's neuroprotective actions are mediated via the Nrf2 pathway. These results underscore BBR's potential in ameliorating motor impairments akin to PD, suggesting its promise in potentially delaying or managing PD symptoms. Further research is warranted to translate these preclinical findings into clinical settings, enhancing our comprehension of BBR's therapeutic prospects in PD.

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BACKGROUND: Neurobrucellosis presents diverse clinical challenges and risks of long-term complications. OBJECTIVE: We aimed to assess the relationship between the duration of antibiotic therapy, clinical factors, and the outcome of neurobrucellosis with a case report combined with a systematic review of the literature. METHODS: We present a case of a 31 years-old man successfully treated at our Institution. We then searched Ovid MEDLINE, Embase and Scopus for articles that encompassed neurobrucellosis cases, duration of treatment, and outcome. The primary outcome was to assess an association between the duration of treatment and the risk of sequelae or relapses. Univariate, multivariate and sensitivity analysis were carried out to define which variables affect​ed​ the clinical outcome. Quality assessment was performed using a dedicated tool. RESULTS: A total of 123 studies were included, totaling 221 patients. Median duration of treatment was 4 months (IQR 3 - 6), 69% patients recovered without sequelae, 27% had sequelae. Additionally, five patients had a relapse, and 4 patients died. Multivariate analysis found that the duration of treatment, age, and the use of ceftriaxone were not associated with a higher risk of sequelae or relapses. A significant association was found for corticosteroids use (OR 0.39, 95% IC 0.16 - 0.96, p = 0.038), motor impairment (OR 0.29, 95% IC 0.14 - 0.62, p = 0.002), and hearing loss (OR 0.037, 95% IC 0.01 - 0.11, p < 0.001). CONCLUSIONS: This study highlights the variability in clinical presentations and treatment approaches for neurobrucellosis. Patients with factors indicating higher sequelae risk require meticulous follow-up.

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BACKGROUND: Our team designed an innovative, observation-based motor impairment measure-the Pediatric Stroke Hemiplegic Motor Impairment Scale (Pedi HEMIs). Here we present the results of a survey describing common practices in the pediatric stroke community and the initial psychometric properties of the upper extremity subscale of the Pedi HEMIs (Pedi HEMIs-UE). METHODS: This is a cross-sectional study whereby participants completed a battery of assessments including the novel Pedi HEMIs-UE. Internal consistency was measured via Cronbach alpha (α). Intraclass correlation (ICC) was used to assess inter-rater reliability (IRR). Concurrent validity was investigated using Pearson or polychoric correlations and simple linear regressions. RESULTS: The study sample consisted of 18 children aged 1.08 to 15 years. Two participants completed two sets of evaluations, totaling 20 data sets. Cronbach α, a measure of internal consistency, was on average 0.91 (range: 0.89 to 0.92). IRR was excellent with the six raters in almost perfect agreement (ICC = 0.91; 95% confidence interval [CI]: 0.83 to 0.96). Pearson correlation coefficient between the Pedi HEMIs-UE and logit Assisting Hand Assessment (AHA)/mini-AHA was -0.938 (95% CI: -0.979 to -0.827, P < 0.001), indicating excellent concurrent validity. CONCLUSIONS: We found excellent feasibility, reliability, and validity of the Pedi HEMIs-UE in a convenience sample of youth with hemiparesis after stroke.

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A reserve in the motor domain may underlie the capacity exhibited by some patients to maintain motor functionality in the face of a certain level of disease. This form of "motor reserve" (MR) could include cortical, cerebellar, and muscular processes. However, a systematic definition has not been provided yet. Clarifying this concept in healthy individuals and patients would be crucial for implementing prevention strategies and rehabilitation protocols. Due to its wide application in the assessment of motor system functioning, non-invasive brain stimulation (NIBS) may support such definition. Here, studies focusing on reserve in the motor domain and studies using NIBS were revised. Current literature highlights the ability of the motor system to create a reserve and a possible role for NIBS. MR could include several mechanisms occurring in the brain, cerebellum, and muscles, and NIBS may support the understanding of such mechanisms.

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Background: The recovery of upper extremity motor impairment after stroke remains a challenging task. The clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS), which is believed to aid in the recovery process, is still uncertain. Methods: A systematic search was conducted in Medline (Ovid), Cochrane and Embase electronic databases from March 28, 2014, to March 28, 2023. The inclusion criteria consisted of randomized controlled trials that assessed the effects of rTMS on the recovery of upper limb motor impairment among stroke patients. Various measurements, including the Fugl Meyer Assessment Upper Extremity Scale (FMA-UE), Brunnstrom recovery stage, Action Research Arm Test (ARAT), and Barthel index, were evaluated both before and after the intervention. Results: Nineteen articles with 865 patients were included. When considering only the rTMS parameters, both inhibitory and excitatory rTMS improved FMA-UE (MD = 1.87, 95% CI = [0.88]-[2.86], p < 0.001) and Barthel index (MD = 9.73, 95% CI = [4.57]-[14.89], p < 0.001). When considering only the severity of upper limb hemiplegia, both less severe (MD = 1.56, 95% CI = [0.64]-[2.49], p < 0.001) and severe (MD = 2.05, 95% CI = [1.09]-[3.00], p < 0.001) hemiplegia benefited from rTMS based on FMA-UE. However, when considering the rTMS parameters, severity of hemiplegia and stroke stages simultaneously, inhibitory rTMS was found to be significantly effective for less severe hemiplegia in the acute and subacute phases (MD = 4.55, 95% CI = [2.49]-[6.60], p < 0.001), but not in the chronic phase based on FMA-UE. For severe hemiplegia, inhibitory rTMS was not significantly effective in the acute and subacute phases, but significantly effective in the chronic phase (MD = 2.10, 95% CI = [0.75]-[3.45], p = 0.002) based on FMA-UE. Excitatory rTMS was found to be significantly effective for less severe hemiplegia in the acute and subacute phases (MD = 1.93, 95% CI = [0.58]-[3.28], p = 0.005) based on FMA-UE. The improvements in Brunnstrom recovery stage and ARAT need further research. Conclusion: The effectiveness of rTMS depends on its parameters, severity of hemiplegia, and stroke stages. It is important to consider all these factors together, as any single grouping method is incomplete.

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Individuals with multiple disabilities are among the most challenging to serve and AAC teams often lack direction in determining effective interventions. The purpose of this scoping review was to summarize the research evidence on AAC interventions for individuals with complex communication needs and simultaneous motor, and visual impairments as part of their multiple disabilities; to consider implications for practice; and to determine gaps and directions for future research. A total of 27 studies were identified and reviewed, involving 55 unique participants with multiple disabilities. Most studies focused on direct intervention to increase requesting or choice-making, with little focus on social communication. Only two studies focused on training communication partners. Results indicated that AAC interventions can be highly effective to increase communication for individuals with multiple disabilities. However, there is an urgent need for increased rigor and more detailed participant information in future AAC intervention research with this population. Future research should investigate AAC intervention to improve social communication and increase language development, not just expression of needs and wants. Future research should focus on the needs of individuals with multiple disabilities from culturally and linguistically diverse backgrounds and on implementation of AAC within natural environments.

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