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Chronic pain is one of the major causes of disability with a tremendous impact on an individual's quality of life and on public health. Transcutaneous vagus nerve stimulation (tVNS) is a safe therapeutic for this condition. We aimed to evaluate its effects in adults with chronic pain. A comprehensive search was performed, including randomized controlled trials published until October 2023, which assessed the effects of noninvasive tVNS. Cohen's d effect size and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were performed. Fifteen studies were included. The results revealed a mean effect size of 0.41 (95% CI 0.17-0.66) in favor of tVNS as compared with control, although a significant heterogeneity was observed (χ2 = 21.7, df = 10, P = 0.02, I 2 = 53.9%). However, when compared with nonactive controls, tVNS shows a larger effect size (0.79, 95% CI 0.25-1.33), although the number of studies was small (n = 3). When analyzed separately, auricular tVNS and cervical tVNS against control, it shows a significant small to moderate effect size, similar to that of the main analysis, respectively, 0.42 (95% CI 0.08-0.76, 8 studies) and 0.36 (95% CI 0.01-0.70, 3 studies). No differences were observed in the number of migraine days for the trials on migraine. This meta-analysis indicates that tVNS shows promise as an effective intervention for managing pain intensity in chronic pain conditions. We discuss the design of future trials to confirm these preliminary results, including sample size and parameters of stimulation.

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Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.

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BACKGROUND: The multifaceted nature of Fibromyalgia syndrome (FM) symptoms has been explored through clusters analysis. OBJECTIVE: To synthesize the cluster research on FM (variables, methods, patient subgroups, and evaluation metrics). METHODS: We performed a systematic review following the PRISMA recommendations. Independent searches were performed on PubMed, Embase, Web of Science, and Cochrane Central, employing the terms "fibromyalgia" and "cluster analysis". We included studies dated to January 2024, using the cluster analysis to assess any physical, psychological, clinical, or biomedical variables in FM subjects, and descriptively synthesized the studies in terms of design, cluster method, and resulting patient profiles. RESULTS: We included 39 studies. Most with a cross-sectional design aiming to classify subsets based on the severity, adjustment, symptomatic manifestations, psychological profiles, and response to treatment, based on demographic and clinical variables. Two to four different profiles were found according to the levels of severity and adjustment to FMS. According to symptom manifestation, two to three clusters described the predominance of pain versus fatigue, and thermal pain sensitivity (less versus more sensitive). Other clusters revealed profiles of personality (pathological versus non-pathological) and psychological vulnerability (suicidal ideation). Additionally, studies identified different responses to treatment (pharmacological and multimodal). CONCLUSION: Several profiles exist within FMS population, which point out to the need for specific treatment options given the different profiles and an efficient allocation of healthcare resources. We notice a need towards more objective measures, and the validation of the cluster results. Further research might investigate some of the assumptions of these findings, which are further discussed in this paper.

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BACKGROUND: Depression and anxiety are non-motor symptoms of Parkinson's disease (PD). Physical exercise is a promising approach to reducing neuropsychological burden. We aimed to comprehensively synthesize evidence regarding the use of exercise for treating depression and anxiety symptoms in PD. METHODS: Systematic review and meta-analysis following PRISMA recommendations. Searches on PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Physiotherapy Evidence Database (PEDro) was conducted. The random-effects model was employed for all analyses with the standardized mean difference as the effect estimate. RESULTS: Fifty records were retrieved, but only 17 studies met the criteria for the meta-analyses. A moderate to large effect was observed for depression (-.71 [95% CI = -.96 to -.46], 11 studies, 728 individuals), and a small to moderate effect for anxiety (-.39 [95% CI = -.65 to -.14], 6 studies, 241 individuals), when comparing exercise to non-exercise controls. Subgroup analysis revealed significant effects from aerobic (-.95 [95% CI = -1.60, -.31]), mind-body (-1.85 [95% CI = -2.63, -1.07]), and resistance modalities (-1.61 [95% CI = -2.40, -.83]) for depression, and from mind-body (-.67 [95% CI = -1.19 to -.15]) and resistance exercises (-1.00 [95% CI = -1.70 to -.30]) for anxiety. CONCLUSION: Physical exercise has a relevant clinical impact on depression and anxiety in PD. We discuss the level of the evidence, the methodological limitations of the studies, and give recommendations.

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Objective: Investigate the relationship between resting-state EEG-measured brain oscillations and clinical and demographic measures in Stroke patients. Methods: We performed a cross-sectional analysis of a cohort study (DEFINE cohort), Stroke arm, with 85 patients, considering demographic, clinical, and stroke characteristics. Resting-state EEG relative power from delta, theta, alpha, and beta oscillations were measured from the central region. Multivariate regression models were used for both affected and non-affected hemispheres. Results: Motor function was negatively associated with Delta and Theta oscillations, while positively associated with Alpha oscillations (both hemispheres). Similarly, cognition levels measured were negatively associated with Delta activity. Depression levels were negatively associated with Alpha activity specifically in the affected hemisphere, while positively associated with Beta activity in both hemispheres. Regarding pain measures, no significant association was observed, while CPM measure showed a positive association with Alpha activity in the non-affected hemisphere. Finally, we found that theta/alpha ratio was negatively associated with motor function and CPM scores. Conclusion: The results lead us to propose a framework for brain oscillations in stroke, whereas Delta and Beta would represent disrupted mal-adaptive brain plasticity and Theta and Alpha would represent compensatory and functional brain oscillations for motor and sensory deficits in stroke, respectively.

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Introduction: Parkinson's disease is a movement disorder that also manifests non-motor symptoms (NMS). Physical exercise is a prominent strategy that can have an impact on NMS; however, the evidence is limited. Our aim was to verify the effects of exercise on NMS, as assessed using general NMS scales. Methods: This study is a systematic review and meta-analysis. Two searches were conducted on the PubMed, Cochrane Library, Scopus, Web of Science, Embase, Science Direct and PEDro databases from September to December 2022. The PEDro scale was used to assess the methodological quality of the studies. Results: Twenty-three studies were included. The interventions were classified as multimodal, aerobic, resistance, dance, conventional physical therapy and other types. Five studies had high risk of bias. Eight studies were included in the meta-analyses. According to the criteria, four studies compared exercise with non-exercise (n=159), two compared multimodal exercise with cognitive/leisure approaches (n=128), and two compared aerobic with conventional exercise (n=40). No statistical differences were observed between exercise and non-exercise (-0.26 (-0.58 to 0.05)) and between multimodal and cognitive approaches (0.21 (-0.14 to 0.55)). However, trends were observed in the direction of exercise and cognitive approaches. A significant difference was observed favouring aerobic over conventional exercise (-0.72 (-1.36 to -0.08)). Conclusions: Our findings suggest that exercise may have an effect on general NMS compared with non-exercise, although only a trend was observed. It was also observed for cognitive approaches over multimodal exercises. Aerobic exercise showed near-large effects compared with conventional exercise.

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BACKGROUND: Transauricular vagus nerve stimulation (taVNS) is being studied as a feasible intervention for stroke, but the mechanisms by which this non-invasive technique acts in the cortex are still broadly unknown. OBJECTIVES: This study aimed to systematically review the current pre-clinical evidence in the auricular vagus nerve stimulation (aVNS) neuroplastic effects in stroke. METHODS: We searched, in December of 2022, in Medline, Cochrane, Embase, and Lilacs databases. The authors executed the extraction of the data on Excel. The risk of bias was evaluated by adapted Cochrane Collaboration's tool for animal studies (SYRCLES's RoB tool). RESULTS: A total of 8 studies published between 2015 and 2022 were included in this review, including 391 animal models. In general, aVNS demonstrated a reduction in neurological deficits (SMD = -1.97, 95% CI -2.57 to -1.36, I2 = 44%), in time to perform the adhesive removal test (SMD = -2.26, 95% CI -4.45 to -0.08, I2 = 81%), and infarct size (SMD = -1.51, 95% CI -2.42 to -0.60, I2 = 58%). Regarding the neuroplasticity markers, aVNS showed to increase microcapillary density, CD31 proliferation, and BDNF protein levels and RNA expression. CONCLUSIONS: The studies analyzed show a trend of results that demonstrate a significant effect of the auricular vagal nerve stimulation in stroke animal models. Although the aggregated results show high heterogeneity and high risk of bias. More studies are needed to create solid conclusions.

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BACKGROUND: Parkinson's disease (PD) is the second most common progressive neurodegenerative disorder. Exercise protocols are promising interventions to improve PD symptoms, however, the best modality and its neural correlates are still unknown. OBJECTIVES: To evaluate the effects of the aerobic, strength and task-oriented upper-limb exercises in motor function, manual dexterity, and brain oscillations of individuals with PD. METHOD: In this clinical trial, 44 PD patients aged 40-80 years will be randomized in four groups: aerobic training (AT), strength training (ST), task-oriented training (TOT), and waiting list group (CG). The AT group will perform 30 min of a cycle ergometer on 50%-70% of the reserve heart rate. The ST group will use equipment for upper limb muscles and will perform two series of 8-12 repetitions for each exercise, and intensity between 50% and 70% of one maximum repetition will be used. The TOT group will perform a program consisting of three activities to enhance reaching, grasping, and manipulation. All the groups will perform three sessions per week for 8 weeks. We will use the UPDRS Motor function section, Nine-Hole Peg Test, and quantitative electroencephalography to measure motor function, manual dexterity, and brain oscillations, respectively. ANOVA and regression models will be used to compare outcomes within and between groups.

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Transcutaneous auricular vagus nerve stimulation (taVNS) is a newer delivery system using a non-invasive stimulation device placed at the ear. taVNS research is focused on clinical trials showing potential therapeutic benefits, however the neurophysiological effects of this stimulation on brain activity are still unclear. We propose a systematic review that aims to describe the effects of taVNS on EEG measures and identify taVNS parameters that can potentially lead to consistent EEG-mediated biomarkers for this therapy. A systematic literature review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) and the Cochrane handbook for systematic reviews. Clinical trials examining EEG parameters were considered, including absolute and relative power, coherence, degree of symmetry, evoked potentials, and peak frequency of all bands. According to our criteria, 18 studies (from 122 articles) were included. Our findings show a general trend towards increased EEG power spectrum activity in lower frequencies, and changes on early components of the ERP related to inhibitory tasks. This review suggests that quantitative electroencephalography can be used to assess the effects of taVNS on brain activity, however more studies are needed to systematically establish the specific effects and metrics that would reflect the non-invasive stimulation through the auricular branch of the vagus nerve.

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The cerebellum receives dopaminergic innervation and expresses the five types of described dopaminergic receptors. The cerebellar function involves both motor movement and cognition, but the role of cerebellar dopaminergic system on these processes remain unclear. The present study explores the behavioral responses to intracerebellar microinjection of dopaminergic agents in motor and emotional memory. For this, naïve Swiss mice had their cerebellar vermis implanted with a guide canula, received a intravermis microinjection of Dopamine, D1-like antagonist SCH-23390 or D2-like antagonist Eticlopride, and underwent a behavioral analysis of motor learning (by a Rotarod and balance beam learning protocol) or aversive memory acquisition (by the inhibitory avoidance task). The mixed-effects analysis was used to evaluate groups performance, followed by Tukey's post hoc when appropriated. In this study, Dopamine, SCH-23390 and Eticlopride at the doses used did not affected motor control and motor learning. In addition, the administration of Dopamine and SCH-233390 had no effects on emotional memory acquisition, but the animals that received the highest dose of Eticlopride had an improvement in aversive memory acquisition, shown by a suppression of its innate preference for the dark compartment of the inhibitory avoidance apparatus following an exposure to a foot shock. We propose that cerebellar dopaminergic D2 receptors seem to participate on the modulation of aversive memory processes, without influencing motor performance at the doses used in this study.

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BACKGROUND: Parkinson's disease (PD) non motor symptoms may present early in the disease course and worsen with advancing disease. Respiratory changes can affect individuals to remain physically active, contributing to a reduction of functionality and quality of life. OBJECTIVE: The aim of this systematic review is to synthesize evidence of respiratory disorders in patients with PD. METHODS: An electronic search was performed up to November 2020 on PubMed-MEDLINE, Embase, Web of Science, Lilacs, Cinahl, and Cochrane using the following keyword combination: [("Parkinson disease") AND ("respiratory function tests" OR "evaluation") AND ("respiratory system" OR "respiration disorders" OR "respiratory muscles")]. RESULTS: The electronic search resulted in 601 references in English or Portuguese. The selection process and data extraction were made by two independent reviewers. We selected 19 studies including cross-sectional studies that investigated the respiratory disorders in patients with PD through pulmonary function, respiratory muscle strength, or physical capacity evaluation. We excluded studies that considered patients with other diseases. Eighteen studies evaluated the pulmonary function in patients with PD, eleven studies verified the influence of PD on respiratory muscle strength, and three studies assessed the physical capacity through functional tests. CONCLUSION: The evidence showed that PD patients have higher chances to present a pulmonary dysfunction, either obstructive or restrictive, when compared to healthy subjects. In addition, these patients present lower respiratory muscle strength and a consequent decrease in physical capacity in endurance exercises. The respiratory impairment in PD seems to be directly related to the progression of the disease.

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INTRODUCTION: Upper limb movements are affected frequently by brain ischemia (BI). Mechanisms involved in recovery and compensatory movements have developed several studies. However, less attention is given to skeletal muscles, where neuromuscular junction (NMJ) has an important role on muscle tropism and functional performance. METHODS: Animals were divided into two groups: control (C) and BI. Then, animals were skilled to perform single-pellet retrieval task, following these procedures: habituation, shaping, and single-pellet retrieval task. BI was induced using stereotaxic surgery in order to apply endothelin-1 in motor cortex, representative of movements of dominant paw. Reaching task performance was evaluated by single-pellet retrieval task 1 day before BI induction, 4 and 15 days after BI induction. After that, biceps, triceps, fingers flexor, and extensor muscles were extracted. NMJ was assessed in morphometric characteristics (total area, total perimeter, and feret). Muscle fiber cross-sectional area and connective tissue percentage were also evaluated for characterization. Student's t test was used for comparisons between C and BI groups. Tau Kendall's correlation was applied among variables from BI group. RESULTS: An increase in all NMJ morphometric parameters, as well as increase of atrophy and fibrosis in BI group compared with C. There was a high level of direct correlation between mean values of NMJ morphometry with percentage of success in reaching task in BI group. CONCLUSION: Brain ischemia-induced NMJ compensatory expansion, muscle atrophy, and fibrosis in forelimb muscles that are related to reaching performance.

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BACKGROUND: Individuals with Parkinson's disease (PD), in addition to motor impairment, may evolve with respiratory and autonomic nervous system disorders. Currently, there are few studies with emphasis on muscle and pulmonary dysfunction and that verify the benefits of inspiratory muscle training (IMT) in this population. AIM: The aim of this study was to evaluate whether IMT is effective for the improvement of respiratory muscle strength, lung function, thoracic mobility, functional capacity and cardiac autonomic function in PD. METHODS: A randomized and controlled trial will be conducted with 26 participants with idiopathic PD, with aged between 50 and 65 years, in the Stages I to III by the Modified Hoehn and Yahr Scale. Respiratory muscle strength will be performed by manovacuometry and lung function by spirometry. Functional capacity will be evaluated by the 6-min walk test and autonomic cardiac function by heart rate variability. In addition, thoracic mobility measurement will also be performed. After the evaluations, these participants will be randomly assigned to two groups: the IMT group with Powerbreathe® , which will perform the eight series of 2 min each, with 1 min of rest between them, totaling 30 min, at 60% of the maximum inspiratory pressure and the control group, who will perform the same training protocol but with the load maintained at 9 cmH2 O. All participants will be submitted to the same motor training protocol. CONCLUSION: It is expected that IMT increases the inspiratory muscle strength, contributing to the improved expiratory muscle strength, lung function, thoracic mobility, functional capacity and cardiac autonomic function in individuals with mild to moderate PD.

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This study aims to evaluate the influence of the degree of difficulty of the activities in Motor Activity Log (MAL) scores for patients with mild, moderate, and severe hemiparesis, and to estimate the correlation between motor impairment levels of hemiparesis and MAL scores in post-stroke patients. Sixty-six patients with chronic hemiparesis (49 with mild-moderate hemiparesis, and 17 with severe hemiparesis) were evaluated by the Fugl-Meyer upper-limb section and versions of MAL for different degrees of motor impairment. The Rasch model was used to analyze the level of difficulty of the activities of the different versions of MAL. The Spearman's correlation tested the relationship between the Fugl-Meyer Assessment upper-limb section and MAL. The MAL version, developed to evaluate patients with severe hemiparesis, does not contain the easier activities as employed by the Rasch analysis. There was positive correlation between the Fugl-Meyer Assessment upper-limb section scores and Amount of Use of the three versions of the MAL (r = 0.76, 0.78, and 0.77). The difficulty of the activities seems to influence the quantity and quality of use of the affected upper limb in individuals with chronic hemiparesis. A new version of MAL is proposed for individuals with severe motor impairment.

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Experimental evidence suggests that the cerebellum plays a more complex role in learning than simply regulating the motor response. Rather, it is thought to play a significant role in the consolidation of emotional memory in mice. Due to the difficulty of interpreting fear and anxiety behaviors-the standard methodology for the study of the histaminergic system and emotional memory-in mice, we propose a behavioral assessment of mice subjected to the Elevated T-maze after histamine microinjection of the cerebellar vermis. Young male Swiss albino mice weighing 25-35g were used. In addition, locomotor activity was tested in an open field test. Our data suggest that histamine did not affect memory consolidation during escape or open field behavior at the doses used in this study. However, we observed a significant increase in inhibitory avoidance on the second day in animals receiving a dose of 6.8nmol/0.5µl, suggesting that histamine facilitates the consolidation of inhibitory avoidance in mice.

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This study investigated the role of H(1) receptor in the state-dependent memory deficit induced by l-histidine (LH) in mice using Trial 1/2 protocol in the elevated plus-maze (EPM). The test was performed for two consecutive days: Trial 1 (T1) and Trial 2 (T2). Before both trials, mice received a combined injection i.p. of saline+saline (SAL/SAL), 500 mg/kg L-histidine+saline (LH/SAL), 500 mg/kg L-histidine+16 mg/kg chlorpheniramine (LH/CPA) or saline+16 mg/kg chlorpheniramine (SAL/CPA). The trials were performed in the EPM 10 min after the last injection. Each animal was placed in the center of the maze facing the open arm and had five minutes to explore it. On both days, test sessions were videotaped. The behavioral measures were scored from videotape. Data were analyzed based on Analysis of Variance (ANOVA) and the Fisher's LSD test. The data showed no effects on anxiety since there was no difference between the SAL/SAL and the other groups in Trial 1, respectively, open arm entries (OAE), open arm time (OAT) and their percentages (%OAE and %OAT). During Trial 2, OAE, OAT, %OAE and %OAT were reduced in mice treated with SAL/SAL, LH/CPA and SAL/CPA, while the group LH/SAL did not show any difference in these measures. No significant changes were observed in enclosed arm entries (EAE), an EPM index of general exploratory activity. Thus, it can be suggested that LH induces emotional memory deficit and the treatment with chlorpheniramine was able to revert this effect, suggesting this action of LH was mediated by the H(1) receptor.

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Diversos estudos disponibilizam evidências sobre características do desempenho motor ecognitivo de indivíduos com Síndrome de Down (SD), porém poucos estudos analisam a força muscular nestes indivíduos. As alterações apresentadas por indivíduos com SD podem manifestar-se funcionalmente e interferir na sua capacidade de desempenhar de forma independente diversas atividades e tarefas da rotina diária. Objetivo: O presente estudo teve como objetivo analisar a influência da textura do objeto na força de preensão palmar em indivíduos com Síndrome de Down. Participaram do estudo dez indivíduos com SD, com idade entre 4 e 30 anos. Método: A análise da força de preensão palmar foi mensurada por meio de um transdutor de força. A tarefa proposta para a coleta dos dados foi realizar a preensão do transdutor, revestido com diferentes texturas, transportá-lo até um ponto previamente demarcado, e posteriormente o retorno à posição inicial. Os dados obtidos foram analisados por meio de estatística descritiva e não-paramétrica. Resultados: Os dados da estatística descritiva permitiram observar que a textura áspera foi a que exigiu menor força de preensão palmar dos participantes neste estudo, no entanto a análise não-paramétrica indicou não haver diferença estatisticamente significativa. Conclusão:Os resultados deste estudo indicam que textura do objeto não influenciou a força de preensão palmar executada pelos indivíduos com Síndrome de Down.

Many studies show evidences about characteristics of the motor and cognitive performance of subjects with Down Syndrome (DS). However, there is lack of studies that analyze the muscular force in these individuals. The alterations found in subjects with DS can impair their function and interfere in the capacity of the subjects to perform many activities and tasks of the daily routine independently. Objective: The purpose of this study was to analyze the influence of object's texture on grip force in subjects with DS. Ten individuals with diagnosis of DS were selected, with age between 4 and 30 years. Methods: The grip force was measured with a transducer with two different textures. The proposed task for data collection was to hold the transducer, covered with two different textures, and carry it until a point previously demarcated, and later return it to the initial position. The data were analyzed through descriptive and nonparametric statistics. Results: It was possible to observe that the rough texture was the one that demanded minor amount of grip force; however the nonparametric analysis indicated that there was no significant difference in grip force among textures. Conclusion: The results of this study indicated that the object's texture did not influence the grip force carried out by individuals with DS.

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