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Bilateral transcutaneous auricular vagus nerve stimulation (taVNS) - a non-invasive neuromodulation technique - has been investigated as a safe and feasible technique to treat many neuropsychiatric conditions. such as epilepsy, depression, anxiety, and chronic pain. Our aim is to investigate the effect of taVNS on neurophysiological processes during emotional and Go/No-Go tasks, and changes in frontal alpha asymmetry. We performed a randomized, double-blind, sham-controlled trial with 44 healthy individuals who were allocated into two groups (the active taVNS group and the sham taVNS group). Subjects received one session of taVNS (active or sham) for 60 min. QEEG was recorded before and after the interventions, and the subjects were assessed while exposed to emotional conditions with sad and happy facial expressions, followed by a Go/No-Go trial. The results demonstrated a significant increase in N2 amplitude in the No-Go condition for the active taVNS post-intervention compared to the sham taVNS after adjusting by handedness, mood, and fatigue levels (p = 0.046), significantly reduced ERD during sad conditions after treatment (p = 0.037), and increased frontal alpha asymmetry towards the right frontal hemisphere during the emotional task condition (p = 0.046). Finally, we observed an interesting neural signature in this study that suggests a bottom-up modulation from brainstem/subcortical to cortical areas as characterized by improved lateralization of alpha oscillations towards the frontal right hemisphere, and changes in ERP during emotional and Go/No-Go tasks that suggests a better subcortical response to the tasks. Such bottom-up effects may mediate some of the clinical effects of taVNS.
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Eletroencefalografia , Emoções , Estimulação do Nervo Vago , Humanos , Masculino , Feminino , Adulto , Emoções/fisiologia , Estimulação do Nervo Vago/métodos , Método Duplo-Cego , Adulto Jovem , Eletroencefalografia/métodos , Função Executiva/fisiologia , Ritmo alfa/fisiologia , Potenciais Evocados/fisiologia , Estimulação Elétrica Nervosa Transcutânea/métodos , Inibição PsicológicaRESUMO
BACKGROUND: The different clinical presentations of fibromyalgia syndrome (FMS) might play independent roles in the unclear etiology of cognitive impairments and depressive symptoms seen in patients with FMS. Understanding how these clinical presentations are associated with the clinical and neurophysiological aspects of FMS is important for the development of effective treatments. AIM: To explore the relationship of memory complaints and depressive symptoms with the different clinical and neurophysiological characteristics of FMS. METHODS: Cross-sectional data analysis from a randomized clinical trial. Baseline demographics and data on physical fitness, sleep, anxiety, depression, cortical excitability, and pain (clinical and mechanistic) from 63 subjects with FMS were used. Multiple linear and logistic association models were constructed. RESULTS: Final regression models including different sets of predictions were statistically significant (P < .001), explaining approximately 50% of the variability in cognitive complaints and depression status. Older subjects had higher levels of anxiety, poorer sleep quality, lower motor threshold, and higher relative theta power in the central area and were more likely to have clinical depression. Higher anxiety, pain, and theta power were associated with a higher likelihood of memory complaints. CONCLUSION: Depression symptoms seem to be associated with transcranial magnetic stimulation-indexed motor threshold and psychosocial variables, whereas memory complaints are associated with pain intensity and higher theta oscillations. These mechanisms might be catalyzed or triggered by some behavioral and clinical features, such as older age, sleep disruption, and anxiety. The correlation with clinical variables suggests that the increasing of theta oscillations is a compensatory response in patients with FMS, which can be explored in future studies to improve the treatment of FMS. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03371225.
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Depressão , Fibromialgia , Transtornos da Memória , Ritmo Teta , Humanos , Fibromialgia/fisiopatologia , Fibromialgia/psicologia , Feminino , Pessoa de Meia-Idade , Estudos Transversais , Transtornos da Memória/fisiopatologia , Adulto , Depressão/fisiopatologia , Masculino , Ritmo Teta/fisiologia , Estimulação Magnética Transcraniana/métodos , Encéfalo/fisiopatologiaRESUMO
BACKGROUND: Clinical predictors of sleep quality in patients with fibromyalgia syndrome (FMS) are still unknown. By identifying these factors, we could raise new mechanistic hypotheses and guide management approaches. We aimed to describe the sleep quality of FMS patients and to explore the clinical and quantitative sensory testing (QST) predictors of poor sleep quality and its subcomponents. METHODS: This study is a cross-sectional analysis of an ongoing clinical trial. We performed linear regression models between sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and demographic, clinical, and QST variables, controlling for age and gender. Predictors for the total PSQI score and its seven subcomponents were found using a sequential modeling approach. RESULTS: We included 65 patients. The PSQI score was 12.78 ± 4.39, with 95.39% classified as poor sleepers. Sleep disturbance, use of sleep medications, and subjective sleep quality were the worst subdomains. We found poor PSQI scores were highly associated with symptom severity (FIQR score and PROMIS fatigue), pain severity, and higher depression levels, explaining up to 31% of the variance. Fatigue and depression scores also predicted the subjective sleep quality and daytime dysfunction subcomponents. Heart rate changes (surrogate of physical conditioning) predicted the sleep disturbance subcomponent. QST variables were not associated with sleep quality or its subcomponents. CONCLUSIONS: Symptom severity, fatigue, pain, and depression (but no central sensitization) are the main predictors of poor sleep quality. Heart rate changes independently predicted the sleep disturbance subdomain (the most affected one in our sample), suggesting an essential role of physical conditioning in modulating sleep quality in FMS patients. This underscores the need for multidimensional treatments targeting depression and physical activity to improve the sleep quality of FMS patients.
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Fibromialgia , Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Humanos , Fibromialgia/diagnóstico , Qualidade do Sono , Sensibilização do Sistema Nervoso Central , Estudos Transversais , Frequência Cardíaca , Fadiga , Sono , Distúrbios do Início e da Manutenção do Sono/complicações , Transtornos do Sono-Vigília/etiologia , Transtornos do Sono-Vigília/complicações , Inquéritos e QuestionáriosRESUMO
This study aimed to investigate clinical and physiological predictors of brain oscillatory activity in patients with fibromyalgia (FM), assessing resting-state power, event-related desynchronization (ERD), and event-related synchronization (ERS) during tasks. We performed a cross-sectional analysis, including clinical and neurophysiological data from 78 subjects with FM. Multivariate regression models were built to explore predictors of electroencephalography bands. Our findings show a negative correlation between beta oscillations and pain intensity; fibromyalgia duration is positively associated with increased oscillatory power at low frequencies and in the beta band; ERS oscillations in the theta and alpha bands seem to be correlated with better symptoms of FM; fatigue has a signature in the alpha band-a positive relationship in resting-state and a negative relationship in ERS oscillations. Specific neural signatures lead to potential clusters of neural adaptation, in which beta oscillatory activity in the resting state represents a more adaptive activity when pain levels are low and stimulus-evoked oscillations at lower frequencies are likely brain compensatory mechanisms. These neurophysiological changes may help to understand the impact of long-term chronic pain in the central nervous system and the descending inhibitory system in fibromyalgia subjects.
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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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Several studies have demonstrated promising results of transcutaneous auricular vagus nerve stimulation (taVNS) in treating various disorders; however, no mechanistic studies have investigated this technique's neural network and autonomic nervous system effects. This study aims to describe how taVNS can affect EEG metrics, HRV, and pain levels. Healthy subjects were randomly allocated into two groups: the active taVNS group and the sham taVNS group. Electroencephalography (EEG) and Heart Rate Variability (HRV) were recorded at baseline, 30 min, and after 60 min of 30 Hz, 200-250 µs taVNS, or sham stimulation, and the differences between the metrics were calculated. Regarding vagal projections, some studies have demonstrated the role of the vagus nerve in modulating brain activity, the autonomic system, and pain pathways. However, more data is still needed to understand the mechanisms of taVNS on these systems. In this context, this study presents methods to provide data for a deeper discussion about the physiological impacts of this technique, which can help future therapeutic investigations in various conditions.
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Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Frequência Cardíaca , Sistema Nervoso Autônomo , Eletroencefalografia , Dor , Nervo VagoRESUMO
BACKGROUND: Transcranial Magnetic Stimulation (TMS) studies examining exercise-induced neuroplasticity in pain populations have produced contradictory findings. We conducted a systematic review to explore how exercise impacts cortical excitability in pain populations using TMS metrics. This review aims to summarize the effect sizes and to understand their sources of heterogeneity. METHODS: We searched multiple databases from inception to December 2022. We included randomized controlled trials (RCTs) with any type of pain population, including acute and chronic pain; exercise interventions were compared to sham exercise or other active interventions. The primary outcomes were TMS metrics, and pain intensity was the secondary outcome. Risk of bias assessment was conducted using the Cochrane tool. RESULTS: This review included five RCTs (n = 155). The main diagnoses were fibromyalgia and cervical dystonia. The interventions included submaximal contractions, aerobic exercise, physical therapy, and exercise combined with transcranial direct current stimulation. Three studies are considered to have a high risk of bias. All five studies showed significant pain improvement with exercise. The neurophysiological data revealed improvements in cortical excitability measured by motor-evoked potentials; standardized mean difference = 2.06, 95% confidence interval 1.35-2.78, I2 = 19%) but no significant differences in resting motor threshold. The data on intracortical inhibition/facilitation (ICI/ICF) was not systematically analyzed, but one study (n = 45) reported higher ICI and lower ICF after exercise. CONCLUSIONS: These findings suggest that exercise interventions positively affect pain relief by modifying corticospinal excitability, but their effects on ICI/ICF are still unclear. While the results are inconclusive, they provide a basis for further exploration in this area of research; future studies should focus on establishing standardized TMS measurements and exercise protocols to ensure consistent and reliable findings. A large-scale RCT that examines various exercise interventions and their effects on cortical excitability could offer valuable insights to optimize its application in promoting neuroplasticity in pain populations.
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Excitabilidade Cortical , Terapia por Exercício , Humanos , Excitabilidade Cortical/fisiologia , Terapia por Exercício/métodos , Estimulação Magnética Transcraniana , Ensaios Clínicos Controlados Aleatórios como Assunto , Manejo da Dor/métodos , Potencial Evocado Motor/fisiologia , Dor Crônica/terapia , Plasticidade Neuronal/fisiologia , Exercício Físico/fisiologiaRESUMO
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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INTRODUCTION: Trypanosoma cruzi infection triggers an inflammatory process with exacerbated production of cytokines that stimulate inflammatory and anti-inflammatory signals, including the efferent anti-inflammatory signal known as the anti-inflammatory cholinergic pathway. Thus, the use of anticholinesterase drugs, such as galantamine, could minimize the inflammatory process caused by this disease. METHODS: For the study at 30, 60, and 90 days, 120 Swiss mice were divided into three groups. Each group was subdivided into four subgroups: uninfected/untreated (CTRL), uninfected/treated (GAL), infected/untreated (INF), and infected/treated (GAL/INF). The infected groups were inoculated intraperitoneally with 0.1 ml of mouse blood containing 5 × 104 trypomastigote forms of the T. cruzi QM2 strain. The galantamine-treated groups received 5 mg/kg of galantamine orally, through pipetting. From each subgroup, the parameters of parasitemia, histopathological analysis, butyrylcholinesterase activity (BuChE), and functional study of the colon were evaluated. RESULTS: BuChE performance was observed when AChE was suppressed, with increased activity in the GAL/INF group similar to the INF group on the 30th day post infection, thus corroborating the absence of a significant difference in parasitic curves and histopathological analysis. CONCLUSIONS: The presence of an inflammatory process and nests of amastigotes, as well as evidence of reactivity to ACh and NOR, suggest that galantamine did not interfere with the colonic inflammatory response or even in colonic tissue parasitism at this stage of Chagas disease.
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Doença de Chagas , Trypanosoma cruzi , Animais , Butirilcolinesterase , Doença de Chagas/tratamento farmacológico , Galantamina , Camundongos , ParasitemiaRESUMO
INTRODUCTION: Ionizing radiation-producing equipment is used in surgical centers to guide invasive procedures. Technological advances have enabled improvements in image quality, which may be accompanied by increased radiation doses in the surgical team. Correct use of personal protective equipment and monitoring of radiation levels are required to a safe practice. OBJECTIVES: To evaluate radiation exposure conditions in occupationally exposed persons working at the Surgical Center at Hospital das Clínicas da Faculdade de Medicina de Botucatu for implementation of radiation protection measures. METHODS: Three different types of fluoroscopy equipment were used: C-arms, a dosimetric system with ionization chambers, and optically stimulated dosimeters. A three-stage evaluation was conducted, consisting of a first stage for observation, a second stage for estimation of kerma rate simulating exposure conditions, and a final stage for dosimetry to estimate the effective dose in workers. RESULTS: The most frequent procedures and the disposition for each team member were determined. Kerma values were estimated for both the principal physician and the assistant physician. The maximum number of annual procedures was also estimated so that the dose limits are not exceeded. CONCLUSIONS: Dosimetry for the surgical team is indicated as an approach to monitor occupational dose levels. The dose rates and effective dose found in this study are low but not negligible. Thus, proper use of equipment and periodic training for workers are still the best options for radiation protection.
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PURPOSE: To evaluate the influence of type and viscosity of composite resins used for root reinforcement in the adhesion of glass-fiber posts to flared root canals. MATERIALS AND METHODS: The crowns of 78 uniradicular permanent teeth were removed and the teeth were endodontically treated. After one week, the roots were prepared for root reinforcement and randomly divided into 6 groups (n = 13): positive control group ([PCG] the root canals were not enlarged), negative control group ([NCG] root canals were enlarged, no reinforcement), and in the remaining 4 groups, root canals were enlarged to receive root reinforcement according to a combination of the factors composite resin type (bulk-fill or conventional) and viscosity (flowable or regular). After fiber post cementation, six slices were obtained from each root (2 each from the cervical, middle, and apical thirds). For each group, 7 teeth underwent push-out bond strength testing, and 6 teeth were evaluated for nanoleakage and Vickers microhardness. Bond strength and nanoleakage data were submitted to two-way ANOVA and Tukey's test (α = 0.05), and microhardness data to one-way ANOVA and Tukey's test (α = 0.05). RESULTS: The root reinforcement groups with regular and flowable bulk-fill composite resins showed statistically superior adhesion results (higher bond strength and less nanoleakage) compared to the negative control in all root regions. Microhardness values were higher in the cervical third followed by the middle third. CONCLUSION: Regular or flowable bulk-fill composite resins should be chosen for root reinforcement of flared root canals prior to fiber post cementation.
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Colagem Dentária , Técnica para Retentor Intrarradicular , Resinas Compostas , Cavidade Pulpar , Análise do Estresse Dentário , Vidro , Teste de Materiais , Cimentos de ResinaRESUMO
Abstract INTRODUCTION: Trypanosoma cruzi infection triggers an inflammatory process with exacerbated production of cytokines that stimulate inflammatory and anti-inflammatory signals, including the efferent anti-inflammatory signal known as the anti-inflammatory cholinergic pathway. Thus, the use of anticholinesterase drugs, such as galantamine, could minimize the inflammatory process caused by this disease. METHODS For the study at 30, 60, and 90 days, 120 Swiss mice were divided into three groups. Each group was subdivided into four subgroups: uninfected/untreated (CTRL), uninfected/treated (GAL), infected/untreated (INF), and infected/treated (GAL/INF). The infected groups were inoculated intraperitoneally with 0.1 ml of mouse blood containing 5 × 104 trypomastigote forms of the T. cruzi QM2 strain. The galantamine-treated groups received 5 mg/kg of galantamine orally, through pipetting. From each subgroup, the parameters of parasitemia, histopathological analysis, butyrylcholinesterase activity (BuChE), and functional study of the colon were evaluated. RESULTS: BuChE performance was observed when AChE was suppressed, with increased activity in the GAL/INF group similar to the INF group on the 30th day post infection, thus corroborating the absence of a significant difference in parasitic curves and histopathological analysis. CONCLUSIONS: The presence of an inflammatory process and nests of amastigotes, as well as evidence of reactivity to ACh and NOR, suggest that galantamine did not interfere with the colonic inflammatory response or even in colonic tissue parasitism at this stage of Chagas disease.