Spatial functional reorganizations can serve as potential biomarkers of post facial palsy synkinesis.

Facial palsy can result in a serious complication known as facial synkinesis, causing both physical and psychological harm to the patients. There is growing evidence that patients with facial synkinesis have brain abnormalities, but the brain mechanisms and underlying imaging biomarkers remain unclear. Here, we employed functional magnetic resonance imaging (fMRI) to investigate brain function in 31 unilateral post facial palsy synkinesis patients and 25 healthy controls during different facial expression movements and at rest. Combining surface-based mass-univariate analysis and multivariate pattern analysis, we identified diffused activation and intrinsic connection patterns in the primary motor cortex and the somatosensory cortex on the patient's affected side. Further, we classified post facial palsy synkinesis patients from healthy subjects with favorable accuracy using the support vector machine based on both task-related and resting-state functional magnetic resonance imaging data. Together, these findings indicate the potential of the identified functional reorganizations to serve as neuroimaging biomarkers for facial synkinesis diagnosis.

Repetitive transcranial magnetic stimulation focusing on patients with neuropathic pain in the upper limb: a randomized sham-controlled parallel trial.

This study aimed to evaluate the efficacy and safety of navigation-guided repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex in patients with neuropathic pain in the upper limb. This randomized, blinded, sham-controlled, parallel trial included a rTMS protocol (10-Hz, 2000 pulses/session) consisting of five daily sessions, followed by one session per week for the next seven weeks. Pain intensity, as well as pain-related disability, quality of life, and psychological status, were assessed. For the primary outcome, pain intensity was measured daily using a numerical rating scale as a pain diary. Thirty patients were randomly assigned to the active rTMS or sham-stimulation groups. In the primary outcome, the decrease (least square [LS] mean ± standard error) in the weekly average of a pain diary at week 9 compared to the baseline was 0.84 ± 0.31 in the active rTMS group and 0.58 ± 0.29 in the sham group (LS mean difference, 0.26; 95% confidence interval, - 0.60 to 1.13). There was no significant effect on the interaction between the treatment group and time point. Pain-related disability score improved, but other assessments showed no differences. No serious adverse events were observed. This study did not show significant pain relief; however, active rTMS tended to provide better results than sham. rTMS has the potential to improve pain-related disability in addition to pain relief.Clinical Trial Registration number: jRCTs052190110 (20/02/2020).

Neuronal Circuit Dysfunction in Amyotrophic Lateral Sclerosis.

The primary neural circuit affected in Amyotrophic Lateral Sclerosis (ALS) patients is the corticospinal motor circuit, originating in upper motor neurons (UMNs) in the cerebral motor cortex which descend to synapse with the lower motor neurons (LMNs) in the spinal cord to ultimately innervate the skeletal muscle. Perturbation of these neural circuits and consequent loss of both UMNs and LMNs, leading to muscle wastage and impaired movement, is the key pathophysiology observed. Despite decades of research, we are still lacking in ALS disease-modifying treatments. In this review, we document the current research from patient studies, rodent models, and human stem cell models in understanding the mechanisms of corticomotor circuit dysfunction and its implication in ALS. We summarize the current knowledge about cortical UMN dysfunction and degeneration, altered excitability in LMNs, neuromuscular junction degeneration, and the non-cell autonomous role of glial cells in motor circuit dysfunction in relation to ALS. We further highlight the advances in human stem cell technology to model the complex neural circuitry and how these can aid in future studies to better understand the mechanisms of neural circuit dysfunction underpinning ALS.

Contribution of neurophysiology to the diagnosis and monitoring of ALS.

This chapter describes the role of neurophysiological techniques in diagnosing and monitoring amyotrophic lateral sclerosis (ALS). Despite many advances, electromyography (EMG) remains a keystone investigation from which to build support for a diagnosis of ALS, demonstrating the pathophysiological processes of motor unit hyperexcitability, denervation and reinnervation. We consider development of the different diagnostic criteria and the role of EMG therein. While not formally recognised by established diagnostic criteria, we discuss the pioneering studies that have demonstrated the diagnostic potential of transcranial magnetic stimulation (TMS) of the motor cortex and highlight the growing evidence for TMS in the diagnostic process. Finally, accurately monitoring disease progression is crucial for the successful implementation of clinical trials. Neurophysiological measures of disease state have been incorporated into clinical trials for over 20 years and we review prominent techniques for assessing disease progression.

Investigating cortical excitability and inhibition in patients with schizophrenia: A TMS-EEG study.

BACKGROUND: Transcranial magnetic stimulation (TMS) combined with electromyography (EMG) has widely been used as a non-invasive brain stimulation tool to assess excitation/inhibition (E/I) balance. E/I imbalance is a putative mechanism underlying symptoms in patients with schizophrenia. Combined TMS-electroencephalography (TMS-EEG) provides a detailed examination of cortical excitability to assess the pathophysiology of schizophrenia. This study aimed to investigate differences in TMS-evoked potentials (TEPs), TMS-related spectral perturbations (TRSP) and intertrial coherence (ITC) between patients with schizophrenia and healthy controls. MATERIALS AND METHODS: TMS was applied over the motor cortex during EEG recording. Differences in TEPs, TRSP and ITC between the patient and healthy subjects were analysed for all electrodes at each time point, by applying multiple independent sample t-tests with a cluster-based permutation analysis to correct for multiple comparisons. RESULTS: Patients demonstrated significantly reduced amplitudes of early and late TEP components compared to healthy controls. Patients also showed a significant reduction of early delta (50-160 ms) and theta TRSP (30-250ms),followed by a reduction in alpha and beta suppression (220-560 ms; 190-420 ms). Patients showed a reduction of both early (50-110 ms) gamma increase and later (180-230 ms) gamma suppression. Finally, the ITC was significantly lower in patients in the alpha band, from 30 to 260 ms. CONCLUSION: Our findings support the putative role of impaired GABA-receptor mediated inhibition in schizophrenia impacting excitatory neurotransmission. Further studies can usefully elucidate mechanisms underlying specific symptoms clusters using TMS-EEG biometrics.

Differential tractography and whole brain connectometry in primary motor area gliomas resection: A feasibility study.

OBJECTIVE: Establish the evolution of the connectome before and after resection of motor area glioma using a comparison of connectome maps and high-definition differential tractography (DifT). METHODS: DifT was done using normalized quantitative anisotropy (NQA) with DSI Studio. The quantitative analysis involved obtaining mean NQA and fractional anisotropy (FA) values for the disrupted pathways tracing the corticospinal tract (CST), and white fiber network changes over time. RESULTS: We described the baseline tractography, DifT, and white matter network changes from two patients who underwent resection of an oligodendroglioma (Case 1) and an IDH mutant astrocytoma, grade 4 (Case 2). CASE 1: There was a slight decrease in the diffusion signal of the compromised CST in the immediate postop. The NQA and FA values increased at the 1-year follow-up (0.18 vs. 0.32 and 0.35 vs. 0.44, respectively). CASE 2: There was an important decrease in the immediate postop, followed by an increase in the follow-up. In the 1-year follow-up, the patient presented with radiation necrosis and tumor recurrence, increasing NQA from 0.18 in the preop to 0.29. Fiber network analysis: whole-brain connectome comparison demonstrated no significant changes in the immediate postop. However, in the 1-year follow up there was a notorious reorganization of the fibers in both cases, showing the decreased density of connections. CONCLUSIONS: Connectome studies and DifT constitute new potential tools to predict early reorganization changes in a patient's networks, showing the brain plasticity capacity, and helping to establish timelines for the progression of the tumor and treatment-induced changes.

Deep brain stimulation of symptom-specific networks in Parkinson's disease.

Deep Brain Stimulation can improve tremor, bradykinesia, rigidity, and axial symptoms in patients with Parkinson's disease. Potentially, improving each symptom may require stimulation of different white matter tracts. Here, we study a large cohort of patients (N = 237 from five centers) to identify tracts associated with improvements in each of the four symptom domains. Tremor improvements were associated with stimulation of tracts connected to primary motor cortex and cerebellum. In contrast, axial symptoms are associated with stimulation of tracts connected to the supplementary motor cortex and brainstem. Bradykinesia and rigidity improvements are associated with the stimulation of tracts connected to the supplementary motor and premotor cortices, respectively. We introduce an algorithm that uses these symptom-response tracts to suggest optimal stimulation parameters for DBS based on individual patient's symptom profiles. Application of the algorithm illustrates that our symptom-tract library may bear potential in personalizing stimulation treatment based on the symptoms that are most burdensome in an individual patient.

Parkinsonism originates in a discrete secondary and dystonia in a primary motor cortical-basal ganglia subcircuit.

Although manifesting contrasting phenotypes, Parkinson's disease and dystonia, the two most common movement disorders, can originate from similar pathophysiology. Previously, we demonstrated that lesioning (silencing) of a discrete dorsal region in the globus pallidus (rodent equivalent to globus pallidus externa) in rats and produced parkinsonism, while lesioning a nearby ventral hotspot-induced dystonia. Presently, we injected fluorescent-tagged multi-synaptic tracers into these pallidal hotspots (n = 36 Long Evans rats) and permitted 4 days for the viruses to travel along restricted connecting pathways and reach the motor cortex before sacrificing the animals. Viral injections in the Parkinson's hotspot fluorescent labeled a circumscribed region in the secondary motor cortex, while injections in the dystonia hotspot labeled within the primary motor cortex. Custom probability mapping and N200 staining affirmed the segregation of the cortical territories for Parkinsonism and dystonia to the secondary and primary motor cortices. Intracortical microstimulation localized territories specifically to their respective rostral and caudal microexcitable zones. Parkinsonian features are thus explained by pathological signaling within a secondary motor subcircuit normally responsible for initiation and scaling of movement, while dystonia is explained by abnormal (and excessive) basal ganglia signaling directed at primary motor corticospinal transmission.

Characteristics of motor evoked potentials in patients with peripheral vascular disease.

With an aging population, it is common to encounter people diagnosed with peripheral vascular disease (PVD). Some will undergo surgeries during which the spinal cord may be compromised and intraoperative neuromonitoring with motor evoked potentials (MEPs) is employed to help mitigate paralysis. No data exist on characteristics of MEPs in older, PVD patients, which would be valuable for patients undergoing spinal cord at-risk surgery or participating in neurophysiological research. Transcranial magnetic stimulation, which can be delivered to the awake patient, was used to stimulate the motor cortex of 20 patients (mean (±SD)) age 63.2yrs (±11.5) with confirmed PVD, every 10 minutes for one hour with MEPs recorded from selected upper and lower limb muscles. Data were compared to that from 20 healthy volunteers recruited for a protocol development study (28yrs (±7.6)). MEPs did not differ between patient's symptomatic and asymptomatic legs. MEP amplitudes were not different for a given muscle between patients and healthy participants. Except for vastus lateralis, disease severity did not correlate with MEP amplitude. There were no differences over time in the coefficient of variation of MEP amplitude at each time point for any muscle in patients or in healthy participants. Although latencies of MEPs were not different between patients and healthy participants for a given muscle, they were longer in older participants. The results obtained suggest PVD alone does not impact MEPs; there were no differences between more symptomatic and less symptomatic legs. Further, in general, disease severity did not corelate with MEP characteristics. With an aging population, more patients with PVD and cardiovascular risk factors will be participating in neurophysiological studies or undergoing surgery where spinal cord integrity is monitored. Our data show that MEPs from these patients can be easily evoked and interpreted.

Aerobic exercise on the treadmill combined with transcranial direct current stimulation on the gait of people with Parkinson's disease: A protocol for a randomized clinical trial.

Gait impairments negatively affect the quality of life of people with Parkinson's disease (PwPD). Aerobic exercise (AE) is an alternative to alleviate these impairments and its combination with transcranial direct current stimulation (tDCS) has demonstrated synergistic effects. However, the effect of multitarget tDCS application (i.e., motor, and prefrontal cortices simultaneously) combined with physical exercise on gait impairments is still little known. Thus, the proposed randomized clinical trial will verify the acute effects of AE combined with tDCS applied on motor and prefrontal cortices separately and simultaneously on gait (spatial-temporal and cortical activity parameters) in PwPD. Twenty-four PwPD in Hoehn & Yahr stages I-III will be recruited for this crossover study. PwPD will practice AE on treadmill simultaneously with the application of anodal tDCS during four intervention sessions on different days (∼ one week of interval). Active tDCS will be applied to the primary motor cortex, prefrontal cortex, and both areas simultaneously (multitarget), with an intensity of 2 mA for 20 min. For sham, the stimulation will remain at 2 mA for 10 s. The AE will last a total of 30 min, consisting of warm-up, main part (20 min with application of tDCS), and recovery. Exercise intensity will be controlled by heart rate. Spatial-temporal and cortical activity parameters will be acquired before and after each session during overground walking, walking with obstacle avoidance, and walking with a cognitive dual task at self-preferred velocity. An accelerometer will be positioned on the fifth lumbar vertebra to obtain the spatial-temporal parameters (i.e., step length, duration, velocity, and swing phase duration). Prefrontal cortex activity will be recorded from a portable functional near-infrared spectroscopy system and oxygenated and deoxygenated hemoglobin concentrations will be analyzed. Two-way ANOVAs with repeated measures for stimulation and moment will be performed. The findings of the study may contribute to improving gait in PwPD. Trial registration: Brazilian Clinical Trials Registry (RBR-738zkp7).

Effects of robot-assisted upper limb training combined with intermittent theta burst stimulation (iTBS) on cortical activation in stroke patients: A functional near-infrared spectroscopy study.

BACKGROUND: The therapeutic effect and mechanism of robot-assisted upper limb training (RT) combined with intermittent theta burst stimulation (iTBS) for stroke patients are unclear. OBJECTIVE: The purpose of this study was to evaluate changes in brain activation after combination therapy and RT alone using functional near-infrared spectroscopy (fNIRS). METHODS: Patients were randomly assigned to two groups (iTBS + RT Group, n = 18, and RT Group, n = 18). Training was conducted five times a week for four weeks. fNIRS was used to measure changes in oxyhemoglobin in both the primary motor cortex (M1) and pre-motor and supplementary motor area (pSMA) during affected limb movement. Fugl-Meyer Assessment-Upper Extremity (FMA-UE) was employed for evaluating the function of upper limbs. RESULTS: Thirty-two patients with subacute stroke completed the study. The cortex of both hemispheres was extensively activated prior to treatment in the RT group. After training, overactivation decreased. The brain activation of the combined treatment group transferred to the affected side after the treatment. There was a notable enhancement in the FMA-UE scores for both groups, with the combined group's progress significantly surpassing that of the RT group. CONCLUSION: RT combined with iTBS can improve the motor function of stroke patients and promote the balance between cerebral hemispheres.

Evoked oscillatory cortical activity during acute pain: Probing brain in pain by transcranial magnetic stimulation combined with electroencephalogram.

Temporal dynamics of local cortical rhythms during acute pain remain largely unknown. The current study used a novel approach based on transcranial magnetic stimulation combined with electroencephalogram (TMS-EEG) to investigate evoked-oscillatory cortical activity during acute pain. Motor (M1) and dorsolateral prefrontal cortex (DLPFC) were probed by TMS, respectively, to record oscillatory power (event-related spectral perturbation and relative spectral power) and phase synchronization (inter-trial coherence) by 63 EEG channels during experimentally induced acute heat pain in 24 healthy participants. TMS-EEG was recorded before, during, and after noxious heat (acute pain condition) and non-noxious warm (Control condition), delivered in a randomized sequence. The main frequency bands (α, ß1, and ß2) of TMS-evoked potentials after M1 and DLPFC stimulation were recorded close to the TMS coil and remotely. Cold and heat pain thresholds were measured before TMS-EEG. Over M1, acute pain decreased α-band oscillatory power locally and α-band phase synchronization remotely in parietal-occipital clusters compared with non-noxious warm (all p < .05). The remote (parietal-occipital) decrease in α-band phase synchronization during acute pain correlated with the cold (p = .001) and heat pain thresholds (p = .023) and to local (M1) α-band oscillatory power decrease (p = .024). Over DLPFC, acute pain only decreased ß1-band power locally compared with non-noxious warm (p = .015). Thus, evoked-oscillatory cortical activity to M1 stimulation is reduced by acute pain in central and parietal-occipital regions and correlated with pain sensitivity, in contrast to DLPFC, which had only local effects. This finding expands the significance of α and ß band oscillations and may have relevance for pain therapies.

Cortico-cortical connectivity is influenced by levodopa in tremor-dominant Parkinson's disease.

Resting tremor is the most common presenting motor symptom in Parkinson's disease (PD). The supplementary motor area (SMA) is a main target of the basal-ganglia-thalamo-cortical circuit and has direct, facilitatory connections with the primary motor cortex (M1), which is important for the execution of voluntary movement. Dopamine potentially modulates SMA and M1 activity, and both regions have been implicated in resting tremor. This study investigated SMA-M1 connectivity in individuals with PD ON and OFF dopamine medication, and whether SMA-M1 connectivity is implicated in resting tremor. Dual-site transcranial magnetic stimulation was used to measure SMA-M1 connectivity in PD participants ON and OFF levodopa. Resting tremor was measured using electromyography and accelerometry. Stimulating SMA inhibited M1 excitability OFF levodopa, and facilitated M1 excitability ON levodopa. ON medication, SMA-M1 facilitation was significantly associated with smaller tremor than SMA-M1 inhibition. The current findings contribute to our understanding of the neural networks involved in PD which are altered by levodopa medication and provide a neurophysiological basis for the development of interventions to treat resting tremor.

Stroke Recovery-Related Changes in Cortical Reactivity Based on Modulation of Intracortical Inhibition.

BACKGROUND: Cortical excitation/inhibition dynamics have been suggested as a key mechanism occurring after stroke. Their supportive or maladaptive role in the course of recovery is still not completely understood. Here, we used transcranial magnetic stimulation (TMS)-electroencephalography coupling to study cortical reactivity and intracortical GABAergic inhibition, as well as their relationship to residual motor function and recovery longitudinally in patients with stroke. METHODS: Electroencephalography responses evoked by TMS applied to the ipsilesional motor cortex were acquired in patients with stroke with upper limb motor deficit in the acute (1 week), early (3 weeks), and late subacute (3 months) stages. Readouts of cortical reactivity, intracortical inhibition, and complexity of the evoked dynamics were drawn from TMS-evoked potentials induced by single-pulse and paired-pulse TMS (short-interval intracortical inhibition). Residual motor function was quantified through a detailed motor evaluation. RESULTS: From 76 patients enrolled, 66 were included (68.2±13.2 years old, 18 females), with a Fugl-Meyer score of the upper extremity of 46.8±19. The comparison with TMS-evoked potentials of healthy older revealed that most affected patients exhibited larger and simpler brain reactivity patterns (Pcluster<0.05). Bayesian ANCOVA statistical evidence for a link between abnormally high motor cortical excitability and impairment level. A decrease in excitability in the following months was significantly correlated with better motor recovery in the whole cohort and the subgroup of recovering patients. Investigation of the intracortical GABAergic inhibitory system revealed the presence of beneficial disinhibition in the acute stage, followed by a normalization of inhibitory activity. This was supported by significant correlations between motor scores and the contrast of local mean field power and readouts of signal dynamics. CONCLUSIONS: The present results revealed an abnormal motor cortical reactivity in patients with stroke, which was driven by perturbations and longitudinal changes within the intracortical inhibition system. They support the view that disinhibition in the ipsilesional motor cortex during the first-week poststroke is beneficial and promotes neuronal plasticity and recovery.

Motor band sign is specific for amyotrophic lateral sclerosis and corresponds to motor symptoms.

OBJECTIVE: Magnetic resonance imaging can detect neurodegenerative iron accumulation in the motor cortex, called the motor band sign. This study aims to evaluate its sensitivity/specificity and correlations to symptomatology, biomarkers, and clinical outcome in amyotrophic lateral sclerosis. METHODS: This prospective study consecutively enrolled 114 persons with amyotrophic lateral sclerosis and 79 mimics referred to Karolinska University Hospital, and also 31 healthy controls. All underwent 3-Tesla brain susceptibility-weighted imaging. Three raters independently assessed motor cortex susceptibility with total and regional motor band scores. Survival was evaluated at a median of 34.2 months after the imaging. RESULTS: The motor band sign identified amyotrophic lateral sclerosis with a sensitivity of 59.6% and a specificity of 91.1% versus mimics and 96.8% versus controls. Higher motor band scores were more common with genetic risk factors (p = 0.032), especially with C9orf72 mutation, and were associated with higher neurofilament light levels (std. ß 0.22, p = 0.019). Regional scores correlated strongly with focal symptoms (medial region vs. gross motor dysfunction, std. ß -0.64, p = 0.001; intermediate region vs. fine motor dysfunction, std. ß -0.51, p = 0.031; lateral region vs. bulbar symptoms std. ß -0.71, p < 0.001). There were no associations with cognition, progression rate, or survival. INTERPRETATION: In a real-life clinical setting, the motor band sign has high specificity but relatively low sensitivity for identifying amyotrophic lateral sclerosis. Associations with genetic risk factors, neurofilament levels and somatotopic correspondence to focal motor weakness suggest that the motor band sign could be a suitable biomarker for diagnostics and clinical trials in amyotrophic lateral sclerosis.

TMS of the left primary motor cortex improves tremor intensity and postural control in primary orthostatic tremor.

A ponto-cerebello-thalamo-cortical network is the pathophysiological correlate of primary orthostatic tremor. Affected patients often do not respond satisfactorily to pharmacological treatment. Consequently, the objective of the current study was to examine the effects of a non-invasive neuromodulation by theta burst repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) and dorsal medial frontal cortex (dMFC) on tremor frequency, intensity, sway path and subjective postural stability in primary orthostatic tremor. In a cross-over design, eight patients (mean age 70.2 ± 5.4 years, 4 female) with a primary orthostatic tremor received either rTMS of the left M1 leg area or the dMFC at the first study session, followed by the other condition (dMFC or M1 respectively) at the second study session 30 days later. Tremor frequency and intensity were quantified by surface electromyography of lower leg muscles and total sway path by posturography (foam rubber with eyes open) before and after each rTMS session. Patients subjectively rated postural stability on the posturography platform following each rTMS treatment. We found that tremor frequency did not change significantly with M1- or dMFC-stimulation. However, tremor intensity was lower after M1- but not dMFC-stimulation (p = 0.033/ p = 0.339). The sway path decreased markedly after M1-stimulation (p = 0.0005) and dMFC-stimulation (p = 0.023) compared to baseline. Accordingly, patients indicated a better subjective feeling of postural stability both with M1-rTMS (p = 0.007) and dMFC-rTMS (p = 0.01). In conclusion, non-invasive neuromodulation particularly of the M1 area can improve postural control and tremor intensity in primary orthostatic tremor by interference with the tremor network.

Acute aerobic exercise at different intensities modulates inhibitory control and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD).

BACKGROUND: This study aimed to investigate the effects of different aerobic exercise intensities on inhibitory control and cortical excitability in adults with attention-deficit/hyperactivity disorder (ADHD). METHODS: The study was conducted in a within-subject design. Twenty-four adults with ADHD completed a stop signal task and received cortical excitability assessment by transcranial magnetic stimulation (TMS) before and after a single session of low-, moderate-, high-intensity aerobic exercise or a control intervention. RESULTS: Acute moderate-, and high-intensity aerobic exercise improved inhibitory control in adults with ADHD. Moreover, the improving effect was similar between moderate-, and high-intensity aerobic exercise conditions. As shown by the brain physiology results, short interval intracortical inhibition was significantly increased following both, moderate- and high-intensity aerobic exercise intervention conditions. Additionally, the alteration of short interval intracortical inhibition and inhibitory control improvement were positively correlated. CONCLUSIONS: The moderate-, and high-intensity aerobic exercise-dependent alterations of cortical excitability in adults with ADHD might partially explain the inhibitory control-improving effects of aerobic exercise in this population.

Anodal tDCS over the motor cortex improves pain but not physical function in chronic chikungunya arthritis: Randomized controlled trial.

BACKGROUND: Chikungunya virus (CHIKV) is a globally prevalent pathogen, with outbreaks occurring in tropical regions. Chronic pain is the main symptom reported and is associated with decreased mobility and disability. Transcranial direct current stimulation (tDCS) is emerging as a new therapeutic tool for chronic arthralgia. OBJECTIVE: To evaluate the effectiveness of 10 consecutive sessions of anodal tDCS on pain (primary outcome) in participants with chronic CHIKV arthralgia. Secondary outcomes included functional status, quality of life, and mood. METHODS: In this randomized, double-blind, placebo-controlled trial, 30 participants with chronic CHIKV arthralgia were randomly assigned to receive either active (n = 15) or sham (n = 15) tDCS. The active group received 10 consecutive sessions of tDCS over M1 using the C3/Fp2 montage (2 mA for 20 min). Visual analog scale of pain (VAS), health assessment questionnaire (HAQ), short-form 36 health survey (SF-36), pain catastrophizing scale, Hamilton anxiety scale (HAS), timed up and go (TUG) test, lumbar dynamometry, 30-s arm curl and 2-min step test were assessed at baseline, day 10 and at 2 follow-up visits. RESULTS: There was a significant interaction between group and time on pain (p = 0.03; effect size 95 % CI 0.9 (-1.67 to -0.16), with a significant time interaction (p = 0.0001). There was no interaction between time and group for the 2-minute step test (p = 0.18), but the groups differed significantly at day 10 (p = 0.01), first follow-up (p = 0.01) and second follow-up (p = 0.03). HAQ and SF-36 improved but not significantly. There was no significant improvement in mental health, and physical tests. CONCLUSION: tDCS appears to be a promising intervention for reducing pain in participants with chronic CHIKV arthralgia, although further research is needed to confirm these findings and explore potential long-term benefits. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (ReBEC): RBR-245rh7.