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During the COVID-19 outbreak, there was a sharp increase in generalized anxiety disorder (GAD). Acupuncture therapy has the advantages of accurate clinical efficacy, safety and reliability, few adverse reactions, and no dependence, and is gradually becoming one of the emerging therapies for treating GAD. We present a study protocol for a randomized clinical trial with the aim of exploring the mechanism of brain plasticity in patients with GAD and evaluate the effectiveness and reliability of acupuncture treatment. Transcranial magnetic stimulation (TMS) will be used to assess cortical excitability in GAD patients and healthy people. Sixty-six GAD patients meeting the inclusion criteria will be randomly divided into two groups: TA group, (treatment with acupuncture and basic western medicine treatment) and SA group (sham acupuncture and basic western medicine treatment). Twenty healthy people will be recruited as the control group (HC). The parameters that will be evaluated are amplitude of motor evoked potentials (MEPs), cortical resting period (CSP), resting motor threshold (RMT), and Hamilton Anxiety Scale (HAMA) score. Secondary results will include blood analysis of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), serotonin (5-HT), and brain-derived nerve growth factor (BDNF). Outcomes will be assessed at baseline and after the intervention (week 8). This study protocol is the first clinical trial designed to detect differences in cerebral cortical excitability between healthy subjects and patients with GAD, and the comparison of clinical efficacy and reliability before and after acupuncture intervention is also one of the main contents of the protocol. We hope to find a suitable non-pharmacological alternative treatment for patients with GAD.
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Background: Essential tremor, the world's most prevalent movement disorder, lacks a clear understanding of its pathophysiology. Propranolol, a non-specific beta-blocker capable of crossing the blood-brain barrier, is a primary choice for essential tremor treatment. While its tremor-reducing effects are generally attributed to peripheral actions, various uses hint at central adrenergic effects. Nevertheless, propranolol's precise impact on the central nervous system in essential tremor subjects remains unexplored. Methods: In this study, we employed transcranial magnetic stimulation to assess the influence of propranolol on the excitability of the primary motor cortex (M1) in patients with essential tremor, compared to an age- and sex-matched control group. Cortical excitability parameters were measured following placebo and propranolol administration, encompassing resting and active motor thresholds, motor evoked potential characteristics, cortical silent period, and the input/output curve. Results: Distinct effects were observed across the two cortical hemispheres. Essential tremor patients displayed inhibition of the left M1 cortex and heightened excitability in the right M1 cortex four hours after propranolol administration, but not following placebo. Conclusions: These findings suggest potential differential noradrenergic excitatory and inhibitory modulation. However, comprehensive understanding necessitates further investigations, including left-handed participants and more diverse essential tremor subpopulations. This study underscores the need for continued exploration to unravel propranolol's complex effects on motor cortex excitability in essential tremor.
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Tremor Essencial , Córtex Motor , Humanos , Propranolol/farmacologia , Propranolol/uso terapêutico , Tremor Essencial/tratamento farmacológico , Movimento , TremorRESUMO
Stroke is a debilitating clinical condition resulting from a brain infarction or hemorrhage that poses significant challenges for motor function restoration. Previous studies have shown the potential of applying transcranial direct current stimulation (tDCS) to improve neuroplasticity in patients with neurological diseases or disorders. By modulating the cortical excitability, tDCS can enhance the effects of conventional therapies. While upper-limb recovery has been extensively studied, research on lower limbs is still limited, despite their important role in locomotion, independence, and good quality of life. As the life and social costs due to neuromuscular disability are significant, the relatively low cost, safety, and portability of tDCS devices, combined with low-cost robotic systems, can optimize therapy and reduce rehabilitation costs, increasing access to cutting-edge technologies for neuromuscular rehabilitation. This study explores a novel approach by utilizing the following processes in sequence: tDCS, a motor imagery (MI)-based brain-computer interface (BCI) with virtual reality (VR), and a motorized pedal end-effector. These are applied to enhance the brain plasticity and accelerate the motor recovery of post-stroke patients. The results are particularly relevant for post-stroke patients with severe lower-limb impairments, as the system proposed here provides motor training in a real-time closed-loop design, promoting cortical excitability around the foot area (Cz) while the patient directly commands with his/her brain signals the motorized pedal. This strategy has the potential to significantly improve rehabilitation outcomes. The study design follows an alternating treatment design (ATD), which involves a double-blind approach to measure improvements in both physical function and brain activity in post-stroke patients. The results indicate positive trends in the motor function, coordination, and speed of the affected limb, as well as sensory improvements. The analysis of event-related desynchronization (ERD) from EEG signals reveals significant modulations in Mu, low beta, and high beta rhythms. Although this study does not provide conclusive evidence for the superiority of adjuvant mental practice training over conventional therapy alone, it highlights the need for larger-scale investigations.
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Interfaces Cérebro-Computador , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Feminino , Humanos , Masculino , Qualidade de Vida , Recuperação de Função Fisiológica/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Estimulação Transcraniana por Corrente Contínua/métodos , Extremidade Superior , Método Duplo-CegoRESUMO
Transcranial Magnetic Stimulation (TMS) serves as a crucial tool in evaluating motor cortex excitability by applying short magnetic pulses to the skull, inducing neuron depolarization in the cerebral cortex through electromagnetic induction. This technique leads to the activation of specific skeletal muscles recorded as Motor-Evoked Potentials (MEPs) through electromyography. Although various methodologies assess cortical excitability with TMS, measuring MEP amplitudes offers a straightforward approach, especially when comparing excitability states pre- and post-interventions designed to alter cortical excitability. Despite TMS's widespread use, the absence of a standardized procedure for such measurements in existing literature hinders the comparison of results across different studies. This paper proposes a standardized procedure for assessing changes in motor cortical excitability using single-pulse TMS pre- and post-intervention. The recommended approach utilizes an intensity equating to half of the MEP's maximum amplitude, thereby ensuring equal likelihood of amplitude increase or decrease, providing a consistent basis for future studies and facilitating meaningful comparisons of results.â¢A method for assessing changes in motor cortical excitability using single-pulse TMS before and after a specified intervention.â¢We recommend using an intensity equal to half of the MEP's maximum amplitude during evaluations to objectively assess motor cortical excitability changes post-intervention.
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Chronic pain is a frequent and burdensome nonmotor symptom of Parkinson's disease (PD). PD-related chronic pain can be classified as nociceptive, neuropathic, or nociplastic, the former being the most frequent subtype. However, differences in neurophysiologic profiles between these pain subtypes, and their potential prognostic and therapeutic implications have not been explored yet. This is a cross-sectional study on patients with PD (PwP)-related chronic pain (ie, started with or was aggravated by PD). Subjects were assessed for clinical and pain characteristics through questionnaires and underwent quantitative sensory tests and motor corticospinal excitability (CE) evaluations. Data were then compared between individuals with nociceptive and non-nociceptive (ie, neuropathic or nociplastic) pains. Thirty-five patients were included (51.4% male, 55.7 ± 11.0 years old), 20 of which had nociceptive pain. Patients with nociceptive PD-related pain had lower warm detection threshold (WDT, 33.34 ± 1.39 vs 34.34 ± 1.72, P = .019) and mechanical detection threshold (MDT, 2.55 ± 1.54 vs 3.86 ± .97, P = .007) compared to those with non-nociceptive pains. They also presented a higher proportion of low rest motor threshold values than the non-nociceptive pain ones (64.7% vs 26.6%, P = .048). In non-nociceptive pain patients, there was a negative correlation between WDT and non-motor symptoms scores (r = -.612, P = .045) and a positive correlation between MDT and average pain intensity (r = .629, P = .038), along with neuropathic pain symptom scores (r = .604, P = .049). It is possible to conclude that PD-related chronic pain subtypes have distinctive somatosensory and CE profiles. These preliminary data may help better frame previous contradictory findings in PwP and may have implications for future trial designs aiming at developing individually-tailored therapies. PERSPECTIVE: This work showed that PwP-related nociceptive chronic pain may have distinctive somatosensory and CE profiles than those with non-nociceptive pain subtypes. These data may help shed light on previous contradictory findings in PwP and guide future trials aiming at developing individually-tailored management strategies.
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Dor Crônica , Dor Nociceptiva , Doença de Parkinson , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Feminino , Doença de Parkinson/complicações , Estudos Transversais , Medição da DorRESUMO
La estimulación magnética transcraneal (EMT) es una técnica no invasiva que consiste en la utilización de campos magnéticos para estimular a las neuronas de la corteza cerebral. Si bien la electricidad se ha pretendido emplear previamente en el campo de la medicina, la historia de la EMT se remonta al descubrimiento de la inducción electromagnética, por Faraday, en el siglo XIX. Sin embargo, no fue hasta la década de 1980 cuando Anthony Barker, en la Universidad de Sheffield, desarrolló el primer dispositivo de EMT. La EMT funciona mediante una bobina colocada en el cuero cabelludo, la cual produce un campo magnético que puede atravesar el cráneo y estimular las neuronas corticales. La intensidad y la frecuencia del campo magnético pueden ajustarse para dirigirse a zonas específicas del cerebro y producir efectos excitatorios e inhibitorios. Los principios de la EMT se basan en el concepto de neuroplasticidad, que se refiere a la capacidad del cerebro para cambiar y adaptarse en respuesta a nuevas experiencias y estímulos. Al estimular las neuronas del cerebro con la EMT, es posible inducir cambios en la actividad neuronal y la conectividad, lo que a su vez puede provocar cambios cognitivos y en el estado de ánimo.
Transcranial magnetic stimulation (TMS) is a noninvasive technique that uses magnetic fields to stimulate neurons in the cerebral cortex. While electricity has previously been intended to be used in the medical field, the history of TMS dates back to the discovery of electromagnetic induction by Faraday in the 19th century. However, it was not until the 1980s when Anthony Barker developed the first TMS device at the University of Sheffield. TMS works by means of a coil placed against the scalp, thereby producing a magnetic field. This magnetic field can pass through the skull and stimulate cortical neurons. The intensity and frequency of the magnetic field can be adjusted to target specific areas of the brain and produce excitatory and inhibitory effects. The principles of TMS are based on the concept of neuroplasticity, which refers to the brain's ability to change and adapt in response to new experiences and stimuli. By stimulating neurons in the brain with TMS, it is possible to cause changes in neuronal activity and connectivity, which in turn can lead to cognitive and mood changes.
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OBJECTIVES: Central neuropathic pain (CNP) is associated with altered corticomotor excitability (CE), which can potentially provide insights into its mechanisms. The objective of this study is to describe the CE changes that are specifically related to CNP. METHODS: We evaluated CNP associated with brain injury after stroke or spinal cord injury (SCI) due to neuromyelitis optica through a battery of CE measurements and comprehensive pain, neurological, functional, and quality of life assessments. CNP was compared to two groups of patients with the same disease: i. with non-neuropathic pain and ii. without chronic pain, matched by sex and lesion location. RESULTS: We included 163 patients (stroke=93; SCI=70: 74 had CNP, 43 had non-neuropathic pain, and 46 were pain-free). Stroke patients with CNP had lower motor evoked potential (MEP) in both affected and unaffected hemispheres compared to non- neuropathic pain and no-pain patients. Patients with CNP had lower amplitudes of MEPs (366 µV ±464 µV) than non-neuropathic (478 ±489) and no-pain (765 µV ± 880 µV) patients, p < 0.001. Short-interval intracortical inhibition (SICI) was defective (less inhibited) in patients with CNP (2.6±11.6) compared to no-pain (0.8±0.7), p = 0.021. MEPs negatively correlated with mechanical and cold-induced allodynia. Furthermore, classifying patients' results according to normative data revealed that at least 75% of patients had abnormalities in some CE parameters and confirmed MEP findings based on group analyses. DISCUSSION: CNP is associated with decreased MEPs and SICI compared to non-neuropathic pain and no-pain patients. Corticomotor excitability changes may be helpful as neurophysiological markers of the development and persistence of pain after CNS injury, as they are likely to provide insights into global CE plasticity changes occurring after CNS lesions associated with CNP.
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Dor Crônica , Neuralgia , Traumatismos da Medula Espinal , Acidente Vascular Cerebral , Humanos , Qualidade de Vida , Traumatismos da Medula Espinal/complicações , Acidente Vascular Cerebral/complicações , Potencial Evocado Motor/fisiologia , Estimulação Magnética Transcraniana/métodosRESUMO
OBJECTIVES: This study aimed to test the effects of transcranial direct current stimulation (tDCS), using different electrode positioning and montages, on physical performance in maximum incremental tests of healthy non-athlete subjects. DESIGN: A double-blinded, crossover, sham-controlled study. METHOD: Fifteen subjects (aged 25.8 ± 5 years, nine women) received one of five different tDCS protocols: (i) anodal tDCS on the primary motor cortex (M1) (a-tDCS/M1), (ii) anodal tDCS on the left temporal cortex (T3) (a-tDCS/T3), (iii) cathodal tDCS on M1 (c-tDCS/M1), (iv) cathodal on T3 (c-tDCS/T3), or (v) sham tDCS. The protocols were assigned in a random order in separate sessions. After tDCS, the volunteers performed the maximal incremental exercise test (MIT) on a cycle ergometer in each session. The following measures were used to evaluate physical performance (primary outcome) during MIT: time to exhaustion (TE), maximum power (MAX-P), and Borg Rating of Perceived Exertion (RPE) scale. In addition, as a secondary outcome measure, we assessed the lower-limb corticospinal excitability and electrical muscular activity. RESULTS: tDCS applied over T3 or M1 did not influence electrical muscular activity or increase physical performance during MIT in healthy non-athlete subjects. However, our data confirmed that a-tDCS on the M1 increases lower-limb cortical excitability. CONCLUSIONS: Our results suggest that tDCS is not effective in improving performance during maximal dynamic exercise in non-athletes. However, we confirmed that the a-tDCS M1 protocol used in this study might increase cortical excitability in the lower limb motor cortex.
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Estimulação Transcraniana por Corrente Contínua , Feminino , Humanos , Potencial Evocado Motor/fisiologia , Exercício Físico/fisiologia , Percepção/fisiologia , Estimulação Magnética Transcraniana/métodosRESUMO
Background/objective: Chronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates. Method: We aimed to assess the association of OPRM1 (A118G and C17T) and brain-derived neurotrophic factor (BDNF [G196A]) polymorphisms with pain-related outcomes and motor cortex excitability metrics (measured by transcranial magnetic stimulation) in 113 knee OA patients with chronic pain. We performed adjusted multivariate regression analyses to compare carriers versus non-carriers in terms of clinical and neurophysiological characteristics at baseline, and treatment response (pain reduction and increased cortical inhibitory tonus) after rehabilitation. Results: Compared to non-carriers, participants with polymorphisms on both OPRM1 (A118G) and BDNF (G196A) genes were less likely to improve pain after rehabilitation (85 and 72% fewer odds of improvement, respectively). Likewise, both carriers of OPRM1 polymorphisms (A118G and C17T) were also less likely to improve cortical inhibition (short intracortical inhibition [SICI], and intracortical facilitation [ICF], respectively). While pain and cortical inhibition improvement did not correlate in the total sample, the presence of OPRM1 (A118G) and BDNF (G196A) polymorphisms moderated this relationship. Conclusions: These results underscore the promising role of combining genetic and neurophysiological markers to endotype the treatment response in this population.
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INTRODUCTION: There is evidence that electroacupuncture (EA) acts through the modulation of brain activity, but little is known about its influence on corticospinal excitability of the primary motor cortex (M1). OBJECTIVE: To investigate the influence of EA parameters on the excitability of M1 in healthy individuals. METHODS: A parallel, double blind, randomized controlled trial in healthy subjects, evaluating the influence of an EA intervention on M1 excitability. Participants had a needle inserted at LI4 in the dominant hand and received electrical stimulation of different frequencies (10 or 100 Hz) and amplitude (sensory or motor threshold) for 20 min. In the control group, only a brief (30 s) electrical stimulation was applied. Single and paired pulse transcranial magnetic stimulation coupled with electromyography was applied before and immediately after the EA intervention. Resting motor threshold, motor evoked potential, short intracortical inhibition and intracortical facilitation were measured. RESULTS: EA increased corticospinal excitability of M1 compared to the control group only when administered with a frequency of 100 Hz at the sensory threshold (p < 0.05). There were no significant changes in the other measures. CONCLUSION: The results suggest that EA with an intensity level at the sensorial threshold and 100 Hz frequency increases the corticospinal excitability of M1. This effect may be associated with a decrease in the activity of inhibitory intracortical mechanisms. TRIAL REGISTRATION NUMBER: U1111-1173-1946 (Registro Brasileiro de Ensaios Clínicos; http://www.ensaiosclinicos.gov.br/).
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Eletroacupuntura , Córtex Motor , Eletromiografia , Potencial Evocado Motor/fisiologia , Humanos , Estimulação Magnética Transcraniana/métodosRESUMO
Introduction: The physiopathology of central post-stroke pain (CPSP) is poorly understood, which may contribute to the limitations of diagnostic and therapeutic advancements. Thus, the current systematic review was conducted to examine, from an integrated perspective, the cortical neurophysiological changes observed via transcranial magnetic stimulation (TMS), focusing on the structural damage, and clinical symptoms in patients with CPSP. Methods: The literature review included the databases EMBASE, PubMed, and ScienceDirect using the following search terms by MeSH or Entree descriptors: [("Cerebral Stroke") AND ("Pain" OR "Transcranial Magnetic Stimulation") AND ("Transcranial Magnetic Stimulation")] (through September 29, 2020). A total of 297 articles related to CPSP were identified. Of these, only four quantitatively recorded cortical measurements. Results: We found four studies with different methodologies and results of the TMS measures. According to the National Institutes of Health (NIH) guidelines, two studies had low methodological quality and the other two studies had satisfactory methodological quality. The four studies compared the motor threshold (MT) of the stroke-affected hemisphere with the unaffected hemisphere or with healthy controls. Two studies assessed other cortical excitability measures, such as cortical silent period (CSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). The main limitations in the interpretation of the results were the heterogeneity in parameter measurements, unknown cortical excitability measures as potential prognostic markers, the lack of a control group without pain, and the absence of consistent and validated diagnosis criteria. Conclusion: Despite the limited number of studies that prevented us from conducting a meta-analysis, the dataset of this systematic review provides evidence to improve the understanding of CPSP physiopathology. Additionally, these studies support the construction of a framework for diagnosis and will help improve the methodological quality of future research in somatosensory sequelae following stroke. Furthermore, they offer a way to integrate dysfunctional neuroplasticity markers that are indirectly assessed by neurophysiological measures with their correlated clinical symptoms.
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Abstract Background: Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal symptoms, primarily attributed to sensitization of somatosensory system carrying pain. Few reports have investigated the impact of fibromyalgia symptoms on cognition, corticomotor excitability, sleepiness, and the sleep quality — all of which can deteriorate the quality of life in fibromyalgia. However, the existing reports are underpowered and have conflicting directions of findings, limiting their generalizability. Therefore, the present study was designed to compare measures of cognition, corticomotor excitability, sleepiness, and sleep quality using standardized instruments in the recruited patients of fibromyalgia with pain-free controls. Methods: Diagnosed cases of fibromyalgia were recruited from the Rheumatology department for the cross-sectional, case-control study. Cognition (Mini-Mental State Examination, Stroop color-word task), corticomotor excitability (Resting motor threshold, Motor evoked potential amplitude), daytime sleepiness (Epworth sleepiness scale), and sleep quality (Pittsburgh sleep quality index) were studied according to the standard procedure. Results: Thirty-four patients of fibromyalgia and 30 pain-free controls were recruited for the study. Patients of fibromyalgia showed decreased cognitive scores (p = 0.05), lowered accuracy in Stroop color-word task (for color: 0.02, for word: 0.01), and prolonged reaction time (< 0.01, < 0.01). Excessive daytime sleepiness in patients were found (< 0.01) and worsened sleep quality (< 0.01) were found. Parameters of corticomotor excitability were comparable between patients of fibromyalgia and pain-free controls. Conclusions: Patients of fibromyalgia made more errors, had significantly increased reaction time for cognitive tasks, marked daytime sleepiness, and impaired quality of sleep. Future treatment strategies may include cognitive deficits and sleep disturbances as an integral part of fibromyalgia management.(AU)
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Humanos , Fibromialgia/diagnóstico , Cognição , Dor Crônica , Higiene do Sono , Excitabilidade Cortical , Tempo de Reação , Medição da Dor/instrumentação , Estudos de Casos e Controles , Estudos Transversais , Teste de Stroop , Estudo ObservacionalRESUMO
Introduction: Although binge eating disorder (BED) is an eating disorder and obesity is a clinical disease, it is known that both conditions present overlapped symptoms related to, at least partially, the disruption of homeostatic and hedonistic eating behavior pathways. Therefore, the understanding of neural substrates, such as the motor cortex excitability assessed by transcranial magnetic stimulation (TMS), might provide new insights into the pathophysiology of BED and obesity. Objectives: (i) To compare, among BED, obesity, ex-obese, and HC (healthy control) subjects, the cortical excitability indexed by TMS measures, such as CSP (cortical silent period; primary outcome), SICI (intracortical inhibition), and ICF (intracortical facilitation; secondary outcome). (ii) To explore the relationship of the CSP, eating behavior (e.g., restraint, disinhibition, and hunger), depressive symptoms, and sleep quality among the four groups (BED, obesity, ex-obese, and HC). Methods: Fifty-nine women [BED (n = 13), obese (n = 20), ex-obese (n = 12), and HC (n = 14)] comprise the total sample for this study. Assessments: cortical excitability measures (CSP, SICI, and ICF), inhibition response task by the Go/No-go paradigm, and instruments to assess the eating psychopathology (Three-Factor Eating Questionnaire, Eating Disorder Examination Questionnaire, and Binge Eating Scale) were used. Results: A MANCOVA analysis revealed that the mean of CSP was longer in the BED group compared with other three groups: 24.10% longer than the obesity group, 25.98% longer than the HC group, and 25.41% longer than the ex-obese group. Pearson's correlations evidenced that CSP was positively associated with both eating concern and binge eating scores. Conclusion: The findings point out that BED patients present longer CSP, which might suggest an upregulation of intracortical inhibition. Additionally, CSP was positively correlated with Binge Eating Scale and eating concern scores. Further studies are needed.
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OBJECTIVES: We investigated sex differences and the influence of brain-derived neurotrophic factor (BDNF) in the descending pain modulatory system (DPMS), as measured by change on the numerical pain scale (NPS; 0-10) during conditioned pain modulation (CPM task; primary outcome) and by function of the corticospinal motor pathway and heat pain thresholds (HPTs; secondary outcomes). METHODS: This cross-sectional study included healthy volunteers ranging in age from 18 to 45 years (32 male and 24 female). Assessment included serum BDNF, HPT, change on the NPS (0-10) during the CPM task, and motor-evoked potential (MEP) using transcranial magnetic stimulation (TMS). RESULTS: The MEP (Mv) amplitude was larger in male participants compared with female participants (mean [SE] = 1.55 [0.34] vs mean [SE] = 1.27 [0.27], respectively, P = 0.001). The mean NPS (0-10) during CPM task changed more substantially for female compared with male participants (mean [SE] = -3.25 [2.01] vs mean [SE] = -2.29 [1.34], respectively, P = 0.040). In addition, a higher serum BDNF (adjusted index for age) was associated with a larger decrease of the NPS during CPM task (P = 0.003), although further regression analyses by sex showed that this was only significant for females (P = 0.010). CONCLUSIONS: Significant sex differences were identified in DPMS function and corticospinal motor pathway integrity. Nevertheless, BDNF was associated with the function of the DPMS in female but not male participants, indicating that sex and neuroplasticity state are crucial factors for pain perception in healthy subjects.
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Fator Neurotrófico Derivado do Encéfalo , Dor , Adolescente , Adulto , Estudos Transversais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Limiar da Dor , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
Background: This prospective study aimed to evaluate the cortical excitability (CE) of patients with brain tumors surrounding or directly involving the corticospinal tract (CST) using navigated transcranial magnetic stimulation (nTMS). Methods: We recruited 40 patients with a single brain tumor surrounding or directly involving the CST as well as 82 age- and sex-matched healthy controls. The patients underwent standard nTMS and CE evaluations. Single and paired pulses were applied to the primary motor area (M1) of both affected and unaffected cerebral hemispheres 1 week before surgery. The CE parameters included resting motor threshold (RMT), motor evoked potential (MEP) ratio for 140 and 120% stimulus (MEP 140/120 ratio), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF). Motor outcome was evaluated on hospital discharge and on 30-day and 90-day postoperative follow-up. Results: In the affected hemispheres of patients, SICI and ICF were significantly higher than in the unaffected hemispheres (p=0.002 and p =0.009, respectively). The 140/120 MEP ratio of patients' unaffected hemispheres was lower than that in controls (p=0.001). Patients with glioblastomas (GBM) had a higher interhemispheric RMT ratio than patients with grade II and III gliomas ( p = 0.018). A weak correlation was observed among the RMT ratio and the preoperative motor score (R 2 = 0.118, p = 0.017) and the 90-day follow-up ( R 2 = 0.227, p = 0.016). Conclusion: Using preoperative nTMS, we found that brain hemispheres affected by tumors had abnormal CE and that patients with GBM had a distinct pattern of CE. These findings suggest that tumor biological behavior might play a role in CE changes.
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BACKGROUND: Decreased short-interval intracortical inhibition (SICI) to transcranial magnetic stimulation (TMS) of the primary motor cortex was described in subjects with restless legs syndrome/Willis-Ekbom disease (RLS/WED). It remained to be determined whether the magnitude of SICI decrease would be similar across levels of RLS/WED severity. Moreover, it was unknown whether, in addition to decreases in SICI, changes in cortical thickness or area could be detected in subjects with RLS/WED compared to controls. The objective of this study was to compare SICI, cortical thickness, and cortical area in subjects with idiopathic mild to moderate RLS/WED, severe to very severe RLS/WED, and controls. METHODS: The severity of RLS/WED was assessed by the International Restless Legs Syndrome Severity Scale (IRLSS). SICI and 3T magnetic resonance imaging (MRI) data of subjects with RLS/WED and controls were compared. A receiver operating characteristic curve for SICI was designed for discrimination of participants with RLS/WED from controls. Cortical thickness and area were assessed by automated surface-based analysis. RESULTS: SICI was significantly reduced in patients with mild to moderate and severe to very severe RLS/WED, compared to controls (one-way analysis of variance: F = 9.62, p < 0.001). Receiver operating characteristic curve analysis predicted RLS/WED when SICI was above 35% (area under the curve = 0.79, 95% CI 0.67-0.91, p < 0.001). Analyses of the whole brain and of regions of interest did not reveal differences in gray matter thickness or area between controls and subjects with RLS/WED. CONCLUSION: SICI is an accurate cortical biomarker that can support the diagnosis of RLS/WED even in subjects with mild symptoms, but cortical thickness and area were not useful for discriminating subjects with this condition from controls.
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Encéfalo/diagnóstico por imagem , Córtex Motor/diagnóstico por imagem , Síndrome das Pernas Inquietas/terapia , Estimulação Magnética Transcraniana/efeitos adversos , Adulto , Encéfalo/fisiopatologia , Brasil/epidemiologia , Estudos de Casos e Controles , Excitabilidade Cortical , Potencial Evocado Motor , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Qualidade de Vida , Receptores de GABA-A/fisiologia , Síndrome das Pernas Inquietas/diagnóstico , Síndrome das Pernas Inquietas/fisiopatologia , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Estimulação Magnética Transcraniana/métodosRESUMO
INTRODUCTION: Persistent idiopathic facial pain is a refractory and disabling condition of unknown mechanism and etiology. It has been suggested that persistent idiopathic facial pain patients have not only peripheral generators of pain, but also central nervous system changes that would contribute to the persistence of symptoms. We hypothesized that persistent idiopathic facial pain would have changes in brain cortical excitability as measured by transcranial magnetic stimulation compared to healthy controls. METHODS: Twenty-nine persistent idiopathic facial pain patients were compared to age- and sex-matched healthy controls and underwent cortical excitability measurements by transcranial magnetic stimulation applied to the cortical representation of the masseter muscle of both hemispheres. Single-pulse stimulation was used to measure the resting motor threshold and suprathreshold motor-evoked potentials. Paired-pulse stimulation was used to assess short intracortical inhibition and intracortical facilitation. Clinical pain and associated symptoms were assessed with validated tools. RESULTS: Spontaneous pain was found in 27 (93.1%) and provoked pain was found in two (6.9%) persistent idiopathic facial pain patients. The motor-evoked potentials at 120% and 140% were significantly lower for both hemispheres compared to controls. Persistent idiopathic facial pain patients had lower short-interval intracortical inhibition compared with controls. These changes were correlated with some aspects of quality of life, and higher mood symptoms. These neurophysiological alterations were not influenced by analgesic medication, as similar changes were observed in patients with or without central-acting drugs. CONCLUSIONS: Persistent idiopathic facial pain is associated with changes in intracortical modulation involving GABAergic mechanisms, which may be related to certain aspects of the pathophysiology of this chronic pain condition. Trial registration: NTC01746355.
Assuntos
Excitabilidade Cortical/fisiologia , Dor Facial/fisiopatologia , Adulto , Dor Crônica/fisiopatologia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Magnética TranscranianaRESUMO
OBJECTIVES: Goat whey, a usually discarded byproduct from goat cheese manufacturing, is a good source of sialic acid (SA), an oligosaccharide that is involved in processes such as memory and brain excitability. Here, we investigated in rats the effect of dried goat whey (DGW) on memory and the brain excitability-dependent phenomenon known as cortical spreading depression (CSD). We also provide evidence for the involvement of SA in this effect. In addition, we tested animals under unfavorable suckling conditions to evaluate whether nutritional deficiency would modulate DGW action. METHODS: Wistar rats were suckled in litters with 9 and 15 pups (groups L9 and L15, respectively). From postnatal (P) days 7-14, the animals received per gavage 17.45â g of DGW/kg/day, or SA (20â mg/kg/day or 100â mg/kg/day). At P28-30, we tested the animals' memory in the object recognition paradigm. At P35-45 we recorded CSD and analyze its velocity of propagation, amplitude, and duration. RESULTS: In the object recognition test, the L15 DGW-treated rats performed better than the L15-controls. The L15 rats displayed higher CSD velocities compared with L9 groups. The DGW and SA groups exhibited higher CSD velocity than the naïve- and saline-treated controls, regardless the lactation status (P < 0.05). DISCUSSION: Our results documented a novel effect of DGW on memory and CSD. SA dose-dependently facilitated CSD, suggesting its involvement on the DGW action. DGW is considered a potential supplement to improve brain development and function in malnourished children, and this shall be further translationally investigated.