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1.
J Stroke Cerebrovasc Dis ; 29(10): 105107, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32912556

RESUMO

BACKGROUND: Peak neurologic recovery from acute stroke occurs within the first 3 months, and continues at a slower pace for 6 months. OBJECTIVE/HYPOTHESIS: The aim of this pilot study is to clarify the safety and feasibility of multiple diagonal-transcranial direct current stimulation (d-tDCS) sessions up to 3 months with electrodes placed diagonally over the lesional dorsolateral prefrontal cortex and contralesional primary motor cortex for upper limb hemiparesis in acute stroke. METHODS: Five patients with acute stroke (2 with intracerebral hemorrhage and 3 with cerebral infarction) with upper limb paresis participated. d-tDCS (1 mA, 20 min per day) combined with conventional rehabilitation was given starting 7-21 days after stroke onset. Each session consisted of 10 d-tDCS over 2 weeks and patients received 2 sessions in the acute phase and 2 sessions in the subacute phase for a total 40 treatments. Motor function was assessed using Fugl-Meyer Assessment for upper extremity (FMA-UE) before and after each session, and the period to achieve 70% of maximal potential recovery in FMA-UE was evaluated. RESULTS: All 5 patients completed the intervention and showed no adverse effects throughout the protocol. Of these, 3 (60%) achieved 70% predicted scores within 2 months. Regarding therapeutic gains of FMA-UE in each of the 10 sessions in the acute phase, 4 sessions showed great recovery, 3 sessions showed moderate recovery, and 3 sessions showed poor recovery. CONCLUSION: These findings suggest that d-tDCS over 3 months may be safe and feasible for acute stroke patients in the acute to subacute phases and have therapeutic potential to promote recovery of upper limb function, although further randomized, double-blind, sham-controlled trial is warranted with larger sample size.


Assuntos
Atividade Motora , Córtex Motor/fisiopatologia , Paresia/terapia , Córtex Pré-Frontal/fisiopatologia , Acidente Vascular Cerebral/terapia , Estimulação Transcraniana por Corrente Contínua , Extremidade Superior/inervação , Idoso , Avaliação da Deficiência , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paresia/diagnóstico , Paresia/fisiopatologia , Projetos Piloto , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Estimulação Transcraniana por Corrente Contínua/efeitos adversos , Resultado do Tratamento
2.
Neurology ; 95(4): e417-e426, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32675074

RESUMO

OBJECTIVE: To determine whether training with a brain-computer interface (BCI) to control an image of a phantom hand, which moves based on cortical currents estimated from magnetoencephalographic signals, reduces phantom limb pain. METHODS: Twelve patients with chronic phantom limb pain of the upper limb due to amputation or brachial plexus root avulsion participated in a randomized single-blinded crossover trial. Patients were trained to move the virtual hand image controlled by the BCI with a real decoder, which was constructed to classify intact hand movements from motor cortical currents, by moving their phantom hands for 3 days ("real training"). Pain was evaluated using a visual analogue scale (VAS) before and after training, and at follow-up for an additional 16 days. As a control, patients engaged in the training with the same hand image controlled by randomly changing values ("random training"). The 2 trainings were randomly assigned to the patients. This trial is registered at UMIN-CTR (UMIN000013608). RESULTS: VAS at day 4 was significantly reduced from the baseline after real training (mean [SD], 45.3 [24.2]-30.9 [20.6], 1/100 mm; p = 0.009 < 0.025), but not after random training (p = 0.047 > 0.025). Compared to VAS at day 1, VAS at days 4 and 8 was significantly reduced by 32% and 36%, respectively, after real training and was significantly lower than VAS after random training (p < 0.01). CONCLUSION: Three-day training to move the hand images controlled by BCI significantly reduced pain for 1 week. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that BCI reduces phantom limb pain.


Assuntos
Interfaces Cérebro-Computador , Imaginação/fisiologia , Córtex Motor/fisiopatologia , Membro Fantasma/reabilitação , Robótica , Adulto , Idoso , Estudos Cross-Over , Mãos , Humanos , Magnetoencefalografia , Masculino , Pessoa de Meia-Idade , Movimento , Membro Fantasma/fisiopatologia
3.
J Neuroeng Rehabil ; 17(1): 72, 2020 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-32527268

RESUMO

BACKGROUND: Dual transcranial direct current stimulation (tDCS) to the bilateral primary motor cortices (M1s) has potential benefits in chronic stroke, but its effects in subacute stroke, when behavioural effects might be expected to be greater, have been relatively unexplored. Here, we examined the neurophysiological effects and the factors influencing responsiveness of dual-tDCS in subacute stroke survivors. METHODS: We conducted a randomized sham-controlled crossover study in 18 survivors with first-ever, unilateral subcortical ischaemic stroke 2-4 weeks after stroke onset and 14 matched healthy controls. Participants had real dual-tDCS (with an ipsilesional [right for controls] M1 anode and a contralesional M1 [left for controls] cathode; 2 mA for 20mins) and sham dual-tDCS on separate days, with concurrent paretic [left for controls] hand exercise. Using transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG), we recorded motor evoked potentials (MEPs), the ipsilateral silent period (iSP), short-interval intracortical inhibition, and finger movement-related cortical oscillations before and immediately after tDCS. RESULTS: Stroke survivors had decreased excitability in ipsilesional M1 with a relatively excessive transcallosal inhibition from the contralesional to ipsilesional hemisphere at baseline compared with controls, as quantified by decreased MEPs and increased iSP duration. Dual-tDCS led to increased MEPs and decreased iSP duration in ipsilesional M1. The magnitude of the tDCS-induced MEP increase in stroke survivors was predicted by baseline contralesional-to-ipsilesional transcallosal inhibition (iSP) ratio. Baseline post-movement synchronization in α-band activity in ipsilesional M1 was decreased after stroke compared with controls, and its tDCS-induced increase correlated with upper limb score in stroke survivors. No significant adverse effects were observed during or after dual-tDCS. CONCLUSIONS: Task-concurrent dual-tDCS in subacute stroke can safely and effectively modulate bilateral M1 excitability and inter-hemispheric imbalance and also movement-related α-activity.


Assuntos
Córtex Motor/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/terapia , Estimulação Transcraniana por Corrente Contínua/métodos , Adulto , Idoso , Estudos Cross-Over , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Magnetoencefalografia/métodos , Masculino , Pessoa de Meia-Idade , Movimento/fisiologia , Estimulação Magnética Transcraniana/métodos , Extremidade Superior
4.
J Neuroeng Rehabil ; 17(1): 73, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32539812

RESUMO

BACKGROUND: Non-invasive brain stimulation techniques have been shown in several studies to improve the motor recovery of the affected upper-limbs in stroke patients. This study aims to investigate whether or not cathodal transcranial direct current stimulation (c-tDCS), combined with virtual reality (VR), is superior to VR alone in reducing motor impairment and improving upper limb function and quality of life in stroke patients. METHODS: Forty patients who suffered ischemic stroke between 2 weeks to 12 months were recruited for this single-blind randomized control trial. The patients were randomly assigned either to an experimental group who receiving c-tDCS and VR, or a control group receiving sham stimulation and VR. The cathodal electrode was positioned over the primary motor cortex (M1) of the unaffected hemisphere. The treatment session consisted of 20 min of daily therapy, for 10 sessions over a 2-week period. The outcome measures were the Fugl-Meyer Upper Extremity (FM-UE), the Action Research Arm Test (ARAT) and the Barthel Index (BI). RESULTS: The two groups were comparable in demographic characteristic and motor impairment. After 2 weeks of intervention, both groups demonstrated significant improvement in FM-UE, ARAT and BI scores (P<0.05).The experiment group demonstrated more improvement in FM-UE than the control group (10.1 vs. 6.4, p = 0.003) and, ARAT (7.0 vs 3.6, p = 0.026) and BI (12.8 vs 8.5, p = 0.043). CONCLUSIONS: The findings from our study support that c-tDCS, along with VR, can facilitate a stronger beneficial effect on upper limb motor impairment, function and quality of life than VR alone in patients with ischemic stroke. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (ChiCTR1800019386) in November 8, 2018-Retrospectively registered.


Assuntos
Recuperação de Função Fisiológica/fisiologia , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua/métodos , Terapia de Exposição à Realidade Virtual/métodos , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Método Simples-Cego , Acidente Vascular Cerebral/fisiopatologia , Estimulação Transcraniana por Corrente Contínua/efeitos adversos , Extremidade Superior/fisiopatologia
5.
Stroke ; 51(7): 2170-2178, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32568657

RESUMO

BACKGROUND AND PURPOSE: Motor deficit is the most common disability after stroke, and early prediction of motor outcome is critical for early interventions. Here, we constructed a fine map of the corticospinal tract (CST) for early prediction of motor outcome and for understanding the secondary brain changes after subcortical stroke. METHODS: Diffusion spectrum imaging data from 50 healthy adults were used to reconstruct fine maps of CST with different origins, including primary motor area (M1), primary sensory area (S1), premotor cortex, and supplementary motor area (SMA). Their diffusion properties correlated with motor functions in healthy adults. The impacts of the impairments of different CST on motor outcomes and on structural and functional changes of brain were investigated in 136 patients with subcortical stroke by combining CST damage-symptom association study and voxel-based lesion-symptom mapping. RESULTS: In healthy adults, the isotropy of M1 fiber correlated with walking endurance and that of SMA fiber with motor dexterity. In chronic stroke patients, the integrity of M1 and SMA fibers showed the most significant correlation with motor deficits. The percentage of early damage of M1 and SMA fibers correlated with that of chronic motor deficits. Voxel-based lesion-symptom mapping revealed that acute stroke lesions in the bilateral M1 and right SMA fibers were associated with chronic motor deficits. The early damage of M1 fiber negatively correlated with the integrity of M1-M1 fiber, and the early damage of SMA fiber negatively correlated with gray matter volume of the contralateral cerebellum in the chronic stage. CONCLUSIONS: The CST that originated from the M1 and SMA are closely associated with motor outcomes and brain structural changes, and the fine maps of CST from these 2 cortical areas are useful in assessing and predicting long-term motor outcome in patients with subcortical stroke.


Assuntos
Mapeamento Encefálico/métodos , Atividade Motora/fisiologia , Córtex Motor/fisiopatologia , Tratos Piramidais/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/diagnóstico por imagem , Neuroimagem/métodos , Tratos Piramidais/diagnóstico por imagem , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/complicações
6.
Nat Commun ; 11(1): 2388, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404907

RESUMO

Deep brain stimulation (DBS) of the subthalamic nucleus is a symptomatic treatment of Parkinson's disease but benefits only to a minority of patients due to stringent eligibility criteria. To investigate new targets for less invasive therapies, we aimed at elucidating key mechanisms supporting deep brain stimulation efficiency. Here, using in vivo electrophysiology, optogenetics, behavioral tasks and mathematical modeling, we found that subthalamic stimulation normalizes pathological hyperactivity of motor cortex pyramidal cells, while concurrently activating somatostatin and inhibiting parvalbumin interneurons. In vivo opto-activation of cortical somatostatin interneurons alleviates motor symptoms in a parkinsonian mouse model. A computational model highlights that a decrease in pyramidal neuron activity induced by DBS or by a stimulation of cortical somatostatin interneurons can restore information processing capabilities. Overall, these results demonstrate that activation of cortical somatostatin interneurons may constitute a less invasive alternative than subthalamic stimulation.


Assuntos
Estimulação Encefálica Profunda/métodos , Levodopa/uso terapêutico , Transtornos Parkinsonianos/terapia , Somatostatina/metabolismo , Algoritmos , Animais , Antiparkinsonianos/uso terapêutico , Modelos Animais de Doenças , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Córtex Motor/efeitos dos fármacos , Córtex Motor/metabolismo , Córtex Motor/fisiopatologia , Optogenética/métodos , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/fisiopatologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Células Piramidais/fisiologia , Núcleo Subtalâmico/efeitos dos fármacos , Núcleo Subtalâmico/metabolismo , Núcleo Subtalâmico/fisiopatologia
7.
PLoS One ; 15(5): e0233614, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32453767

RESUMO

Recently, modulatory effects of static magnetic field stimulation (tSMS) on excitability of the motor cortex have been reported. In our previous study we failed to replicate these results. It was suggested that the lack of modulatory effects was due to the use of an auditory oddball task in our study. Thus, we aimed to evaluate the role of an oddball task on the effects of tSMS on motor cortex excitability. In a within-subject-design we compared 10 minutes tSMS with and without oddball task. In one of the two sessions subjects had to solve an auditory oddball task during the exposure to the magnet, whereas there was no task during exposure in the other session. Motor cortex excitability was measured before and after tSMS. No modulation was observed in any condition. However, when data were pooled regarding the order of the sessions, a trend for an increase of excitability was observed in the first session compared to the second session. We now can rule out that the auditory oddball task destroys tSMS effects, as postulated. Our results rather suggest that fluctuations in the amplitudes of single pulse motor evoked potentials may possibly mask weak modulatory effects but may also lead to false positive results if the number of subjects in a study is too low. In addition, there might be a habituation effect to the whole procedure, resulting in less variability when subjects underwent the same experiment twice.


Assuntos
Potencial Evocado Motor/efeitos da radiação , Córtex Motor/efeitos da radiação , Estimulação Magnética Transcraniana/métodos , Adulto , Feminino , Humanos , Campos Magnéticos/efeitos adversos , Masculino , Córtex Motor/fisiopatologia , Estimulação Magnética Transcraniana/efeitos adversos
8.
J Headache Pain ; 21(1): 47, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375638

RESUMO

BACKGROUND: Migraine is a severe and disabling brain disorder, and the exact neurological mechanisms remain unclear. Migraineurs have altered pain perception, and headache attacks disrupt their sensory information processing and sensorimotor integration. The altered functional connectivity of sub-regions of sensorimotor brain areas with other brain cortex associated with migraine needs further investigation. METHODS: Forty-eight migraineurs without aura during the interictal phase and 48 age- and sex-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. We utilized seed-based functional connectivity analysis to investigate whether patients exhibited abnormal functional connectivity between sub-regions of sensorimotor brain areas and cortex regions. RESULTS: We found that patients with migraineurs without aura exhibited disrupted functional connectivities between the sensorimotor areas and the visual cortex, temporal cortex, posterior parietal lobule, prefrontal areas, precuneus, cingulate gyrus, sensorimotor areas proper and cerebellum areas compared with healthy controls. In addition, the clinical data of the patients, such as disease duration, pain intensity and HIT-6 score, were negatively correlated with these impaired functional connectivities. CONCLUSION: In patients with migraineurs without aura, the functional connectivities between the sensorimotor brain areas and other brain regions was reduced. These disrupted functional connectivities might contribute to abnormalities in visual processing, multisensory integration, nociception processing, spatial attention and intention and dysfunction in cognitive evaluation and modulation of pain. Recurrent headache attacks might lead to the disrupted network between primary motor cortex and temporal regions and between primary somatosensory cortex and temporal regions. Pain sensitivity and patient quality of life are closely tied to the abnormal functional connectivity between sensorimotor regions and other brain areas.


Assuntos
Imagem por Ressonância Magnética/métodos , Enxaqueca sem Aura/diagnóstico por imagem , Córtex Motor/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Córtex Somatossensorial/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca sem Aura/fisiopatologia , Córtex Motor/fisiopatologia , Rede Nervosa/fisiopatologia , Dor/diagnóstico por imagem , Dor/fisiopatologia , Qualidade de Vida , Córtex Somatossensorial/fisiopatologia , Lobo Temporal/fisiopatologia , Adulto Jovem
9.
J Neurosci ; 40(24): 4788-4796, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32430296

RESUMO

In humans, γ oscillations in cortical motor areas reflect asynchronous synaptic activity and contribute to plasticity processes. In Parkinson's disease (PD), γ oscillatory activity in the basal ganglia-thalamo-cortical network is altered and the LTP-like plasticity elicited by intermittent theta burst stimulation (iTBS) is reduced in the primary motor cortex (M1). In this study, we tested whether transcranial alternating current stimulation (tACS) delivered at γ frequency promotes iTBS-induced LTP-like plasticity in M1 in PD patients. Sixteen patients (OFF condition) and 16 healthy subjects (HSs) underwent iTBS during γ-tACS (iTBS-γ tACS) and during sham-tACS (iTBS-sham tACS) in two sessions. Motor-evoked potentials (MEPs) evoked by single-pulse transcranial magnetic stimulation and short-interval intracortical inhibition (SICI) were recorded before and after the costimulation. A subgroup of patients also underwent iTBS during ß tACS. iTBS-sham tACS facilitated single-pulse MEPs in HSs, but not in patients. iTBS-γ tACS induced a larger MEP facilitation than iTBS-sham tACS in both groups, with similar values in patients and HSs. In patients, SICI improved after iTBS-γ tACS. The effect produced by iTBS-γ tACS on single-pulse MEPs correlated with disease duration, while changes in SICI correlated with Unified Parkinson's Disease Rating Scale Part III scores. The effect of iTBS-ß tACS on both single-pulse MEPs and SICI was similar to that obtained in the iTBS-sham tACS session. Our data suggest that γ oscillations have a role in the pathophysiology of the abnormal LTP-like plasticity in PD. Entraining M1 neurons at the γ rhythm through tACS may be an effective method to restore impaired plasticity.SIGNIFICANCE STATEMENT In Parkinson's disease, the LTP-like plasticity of the primary motor cortex is impaired, and γ oscillations are altered in the basal ganglia-thalamo-cortical network. Using a combined transcranial magnetic stimulation-transcranial alternating current stimulation approach (iTBS-γ tACS costimulation), we demonstrate that driving γ oscillations restores the LTP-like plasticity in patients with Parkinson's disease. The effects correlate with clinical characteristics of patients, being more evident in less affected patients and weaker in patients with longer disease duration. These findings suggest that cortical γ oscillations play a beneficial role in modulating the LTP-like plasticity of M1 in Parkinson's disease. The iTBS-γ tACS approach may be potentially useful in rehabilitative settings in patients.


Assuntos
Ritmo Gama/fisiologia , Córtex Motor/fisiopatologia , Plasticidade Neuronal/fisiologia , Doença de Parkinson/fisiopatologia , Estimulação Transcraniana por Corrente Contínua , Idoso , Idoso de 80 Anos ou mais , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
Neurobiol Aging ; 92: 43-60, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32422502

RESUMO

TDP-43 aggregates are the defining pathological hallmark for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Strikingly, these TDP-43 proteinopathies are also found in other neurodegenerative diseases, including Alzheimer's disease and are prevalent in the brains of old-aged humans. Furthermore, disease-causal mutations in TDP-43 have been identified for ALS and FTD. Collectively, the evidence indicates that TDP-43 dysfunctions lead to motor and cognitive deficits. To determine whether the mouse line expressing an ALS-linked mutation in TDP-43 (Q331K) can be used to study ALS-FTD spectrum disorders, we performed a systematic and longitudinal behavioral assessment that covered motor and cognitive functions. Deficits in motor and cognitive abilities were observed as early as 3 months of age and persisted through to 12 months of age. Within the cognitive modalities, the hippocampus-mediated spatial learning and memory, and contextual fear conditioning, were normal; whereas the frontal cortex-mediated working memory and cognitive flexibility were impaired. Biochemically, the human TDP-43 transgene downregulates endogenous mouse TDP-43 mRNA and protein, resulting in human TDP-43 protein that is comparable with the physiological level in cerebral cortex and hippocampus. Furthermore, Q331K TDP-43 is largely retained at the nucleus without apparent aggregates. Taken together, our data suggest that motor and frontal cortex may be more vulnerable to disease-linked mutation in TDP-43 and, this mouse model may be used to assess ALS-FTD-related spectrum diseases and the molecular underpinnings associated with the phenotypes.


Assuntos
Esclerose Amiotrófica Lateral/genética , Esclerose Amiotrófica Lateral/fisiopatologia , Cognição , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Lobo Frontal/fisiopatologia , Atividade Motora , Córtex Motor/fisiopatologia , Mutação , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos
11.
World Neurosurg ; 140: 303-307, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32428719

RESUMO

BACKGROUND: Malformations of cortical development (MCDs) often result in mental retardation, intractable epilepsy, neurodevelopmental delay, and contralateral hemiparesis. We describe herein a rare patient with MCD who had developed normally in spite of diffuse hemispheric anomaly of the brain. CASE DESCRIPTION: We report a left-handed 20-year-old healthy man. A magnetic resonance image scan revealed congenital left cerebral hemispheric dysplasia and deficit of the normal anatomical primary motor cortices although he was normally developed without hemiparesis nor aphasia. Diffusion tensor tractography showed unusual fiber radiation from the left cerebral peduncle to the much more rostral and lateral cerebral cortices compared with normal anatomy. Right finger flexion-extension task showed activation in that area on functional magnetic resonance imaging. CONCLUSIONS: Even in a congenital hemispheric dysplasia, the contralateral fine finger movement may still depend on the dysplastic hemisphere. On the other hand, speech and the other gross movements including leg, foot, and arm can be compensated with the ipsilateral normal cerebral cortices.


Assuntos
Dedos/fisiologia , Lateralidade Funcional/fisiologia , Córtex Motor/fisiopatologia , Movimento/fisiologia , Imagem de Tensor de Difusão , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Motor/diagnóstico por imagem , Adulto Jovem
12.
J Fluency Disord ; 64: 105763, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32361030

RESUMO

Developmental stuttering is a frequent neurodevelopmental disorder with a complex neurobiological basis. Robust neural markers of stuttering include imbalanced activity of speech and motor related brain regions, and their impaired structural connectivity. The dynamic interaction of cortical regions is regulated by the cortico-basal ganglia-thalamo-cortical system with the supplementary motor area constituting a crucial cortical site. The SMA integrates information from different neural circuits, and manages information about motor programs such as self-initiated movements, motor sequences, and motor learning. Abnormal functioning of SMA is increasingly reported in stuttering, and has been recently indicated as an additional "neural marker" of DS: anatomical and functional data have documented abnormal structure and activity of the SMA, especially in motor and speech networks. Its connectivity is often impaired, especially when considering networks of the left hemisphere. Compatibly, recent data suggest that, in DS, SMA is part of a poorly synchronized neural network, thus resulting in a likely substrate for the appearance of DS symptoms. However, as evident when considering neural models of stuttering, the role of SMA has not been fully clarified. Herein, the available evidence is reviewed, which highlights the role of the SMA in DS as a neural "hub", receiving and conveying altered information, thus "gating" the release of correct or abnormal motor plans.


Assuntos
Encéfalo/fisiopatologia , Córtex Motor/fisiopatologia , Gagueira/diagnóstico , Adulto , Feminino , Humanos , Masculino
13.
Medicine (Baltimore) ; 99(14): e19495, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243365

RESUMO

INTRODUCTION: Upper extremity motor impairment is one of the major sequelae of stroke, resulting in limitations of activities of daily living. Recently, contralesional cortical activation has been reported to be important for motor recovery in stroke patients with severe upper extremity hemiparesis due to the extensive corticospinal tract involvement. We therefore designed this study to investigate the effects of contralesional anodal transcranial direct current stimulation (tDCS), which induces cortical activation, in stroke patients with severe upper extremity motor impairment. METHODS AND ANALYSIS: We will recruit patients with subacute stroke (<3 months after onset) with unilateral upper extremity weakness who meet the following criteria: Shoulder Abduction and Finger Extension (SAFE) score below 8, Fugl-Meyer Assessment for upper extremity (FMA-UE) score ≤25, and absent motor evoked potential (MEP) response on the affected extensor carpi radialis muscle. Subjects will be randomly allocated to either the intervention (n = 18) or the control group (n = 18). The intervention group will undergo 10 sessions of robotic arm rehabilitation with simultaneous anodal tDCS over the contralesional premotor area, whereas the control group will receive sham tDCS during the same sessions. One daily session consists of 25 minutes.The primary outcome measure of this study is the Fugl-Meyer Assessment score of the upper extremity; the secondary outcome measures are the Korean version of the Modified Barthel Index, the Brunnstrom stage of the affected arm and hand, the Box and Block Test, the Modified Ashworth Scale, the Manual Muscle Power Test, and the patient's encephalographic laterality index. DISCUSSION: Findings of this study will help to establish an individualized tDCS protocol according to the stroke severity and to find out the EEG parameters to predict the better recovery in subacute stroke patients with severe upper extremity hemiparesis. ETHICS AND DISSEMINATION: The study was approved by the Seoul National University Bundang Hospital Institutional Review Board (IRB No. B-1806-475-006) and will be carried out in accordance with the approved guidelines. The results of the trial will be submitted for publication in a peer-reviewed journal.


Assuntos
Paresia/reabilitação , Reabilitação do Acidente Vascular Cerebral/métodos , Estimulação Transcraniana por Corrente Contínua/métodos , Extremidade Superior , Atividades Cotidianas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Potencial Evocado Motor , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Recuperação de Função Fisiológica , Adulto Jovem
14.
J Headache Pain ; 21(1): 34, 2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32299338

RESUMO

BACKGROUND: Short-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features. METHODS: SAI was obtained by conditioning the transcranial magnetic stimulation-induced motor evoked potential (MEP) with an electric stimulus on the median nerve at the wrist with random stimulus intervals corresponding to the latency of individual somatosensory evoked potentials (SSEP) N20 plus 2, 4, 6, or 8 ms. We recruited 30 migraine without aura patients, 16 between (MO), 14 during an attack (MI), and 16 healthy volunteers (HV). We calculated the slope of the linear regression between the unconditioned MEP amplitude and the 4-conditioned MEPs as a measure of SAI. We also measured SSEP amplitude habituation, and high-frequency oscillations (HFO) as an index of thalamo-cortical activation. RESULTS: Compared to HV, SAI, SSEP habituation and early SSEP HFOs were significantly reduced in MO patients between attacks, but enhanced during an attack. There was a positive correlation between degree of SAI and amplitude of early HFOs in HV, but not in MO or MI. CONCLUSIONS: The migraine cycle-dependent variations of SAI and SSEP HFOs are further evidence that facilitatory thalamocortical activation (of GABAergic networks in the motor cortex for SAI), likely to be cholinergic, is reduced in migraine between attacks, but increased ictally.


Assuntos
Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Transtornos de Enxaqueca/fisiopatologia , Córtex Motor/fisiopatologia , Inibição Neural/fisiologia , Tálamo/fisiopatologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Nervo Mediano/fisiopatologia , Estimulação Magnética Transcraniana , Adulto Jovem
15.
J Neurosci ; 40(17): 3478-3490, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32241836

RESUMO

Gamma-band oscillations (GBOs) elicited by transient nociceptive stimuli are one of the most promising biomarkers of pain across species. Still, whether these GBOs reflect stimulus encoding in the primary somatosensory cortex (S1) or nocifensive behavior in the primary motor cortex (M1) is debated. Here we recorded neural activity simultaneously from the brain surface as well as at different depths of the bilateral S1/M1 in freely-moving male rats receiving nociceptive stimulation. GBOs measured from superficial layers of S1 contralateral to the stimulated paw not only had the largest magnitude, but also showed the strongest temporal and phase coupling with epidural GBOs. Also, spiking of superficial S1 interneurons had the strongest phase coherence with epidural GBOs. These results provide the first direct demonstration that scalp GBOs, one of the most promising pain biomarkers, reflect neural activity strongly coupled with the fast spiking of interneurons in the superficial layers of the S1 contralateral to the stimulated side.SIGNIFICANCE STATEMENT Nociceptive-induced gamma-band oscillations (GBOs) measured at population level are one of the most promising biomarkers of pain perception. Our results provide the direct demonstration that these GBOs reflect neural activity coupled with the spike firing of interneurons in the superficial layers of the primary somatosensory cortex (S1) contralateral to the side of nociceptive stimulation. These results address the ongoing debate about whether nociceptive-induced GBOs recorded with scalp EEG or epidurally reflect stimulus encoding in the S1 or nocifensive behavior in the primary motor cortex (M1), and will therefore influence how experiments in pain neuroscience will be designed and interpreted.


Assuntos
Ritmo Gama/fisiologia , Córtex Motor/fisiopatologia , Nociceptividade/fisiologia , Dor/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Potenciais de Ação/fisiologia , Animais , Potenciais Somatossensoriais Evocados/fisiologia , Interneurônios/fisiologia , Masculino , Percepção da Dor/fisiologia , Ratos
16.
J Neurosci ; 40(17): 3385-3407, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32241837

RESUMO

Functional recovery after cortical injury, such as stroke, is associated with neural circuit reorganization, but the underlying mechanisms and efficacy of therapeutic interventions promoting neural plasticity in primates are not well understood. Bone marrow mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), which mediate cell-to-cell inflammatory and trophic signaling, are thought be viable therapeutic targets. We recently showed, in aged female rhesus monkeys, that systemic administration of MSC-EVs enhances recovery of function after injury of the primary motor cortex, likely through enhancing plasticity in perilesional motor and premotor cortices. Here, using in vitro whole-cell patch-clamp recording and intracellular filling in acute slices of ventral premotor cortex (vPMC) from rhesus monkeys (Macaca mulatta) of either sex, we demonstrate that MSC-EVs reduce injury-related physiological and morphologic changes in perilesional layer 3 pyramidal neurons. At 14-16 weeks after injury, vPMC neurons from both vehicle- and EV-treated lesioned monkeys exhibited significant hyperexcitability and predominance of inhibitory synaptic currents, compared with neurons from nonlesioned control brains. However, compared with vehicle-treated monkeys, neurons from EV-treated monkeys showed lower firing rates, greater spike frequency adaptation, and excitatory:inhibitory ratio. Further, EV treatment was associated with greater apical dendritic branching complexity, spine density, and inhibition, indicative of enhanced dendritic plasticity and filtering of signals integrated at the soma. Importantly, the degree of EV-mediated reduction of injury-related pathology in vPMC was significantly correlated with measures of behavioral recovery. These data show that EV treatment dampens injury-related hyperexcitability and restores excitatory:inhibitory balance in vPMC, thereby normalizing activity within cortical networks for motor function.SIGNIFICANCE STATEMENT Neuronal plasticity can facilitate recovery of function after cortical injury, but the underlying mechanisms and efficacy of therapeutic interventions promoting this plasticity in primates are not well understood. Our recent work has shown that intravenous infusions of mesenchymal-derived extracellular vesicles (EVs) that are involved in cell-to-cell inflammatory and trophic signaling can enhance recovery of motor function after injury in monkey primary motor cortex. This study shows that this EV-mediated enhancement of recovery is associated with amelioration of injury-related hyperexcitability and restoration of excitatory-inhibitory balance in perilesional ventral premotor cortex. These findings demonstrate the efficacy of mesenchymal EVs as a therapeutic to reduce injury-related pathologic changes in the physiology and structure of premotor pyramidal neurons and support recovery of function.


Assuntos
Lesões Encefálicas/terapia , Vesículas Extracelulares , Células-Tronco Mesenquimais , Córtex Motor/patologia , Células Piramidais/patologia , Recuperação de Função Fisiológica/fisiologia , Animais , Lesões Encefálicas/patologia , Lesões Encefálicas/fisiopatologia , Modelos Animais de Doenças , Feminino , Macaca mulatta , Masculino , Córtex Motor/fisiopatologia , Plasticidade Neuronal/fisiologia , Células Piramidais/fisiologia
17.
J Clin Neurosci ; 76: 208-210, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32284289

RESUMO

Dystonia is a disabling movement disorder characterized by co-contraction of antagonist and agonist muscles, leading to abnormal sustained postures and impaired motor control. Cervical Dystonia (CD) and Hand Focal Dystonia (HFD) have been the most common forms of focal dystonia (FD). Do Non-Invasive Brain Neuromodulation (NIBS) such as Transcranial Direct Current Stimulation (tDCS) and repetitive Transcranial Magnetic Stimulation (rTMS) modulate the excitability of the connections between the motor cortical areas and may represent a therapeutic alternative for focal dystonia? Herein, we reported three cases of focal dystonia, two of them with cervical dystonia (CD) and one with hand focal dystonia (HFD), treated with NIBS combined to kinesiotherapy. The patients were daily submitted to 15 sessions of NIBS combined simultaneously with kinesiotherapy. CD patients were treated with tDCS (2 mA, 20 min, over the primary motor cortex), and HFD patient with rTMS (1 Hz, 1200 pulses, 80% of resting motor threshold, over the premotor cortex). For the CD patient's assessment, the Modified Toronto Scale for Cervical Dystonia Assessment (MTS), quiet balance test, and visual postural assessment were applied to observe the therapeutic effects. Quality handwriting analysis, tremor acceleration amplitudes, and the Wrinter's Cramp Rating Scale (WCRS) were used to assess the NIBS effect on HFD symptoms. Patients were evaluated before (pretest), immediately after (posttest), and three months after treatment (retention). NIBS associated with kinesiotherapy produced a long-term improvement of dystonia symptoms in all three patients. rTMS and tDCS associated with kinesiotherapy showed to be useful and safe to relief the dystonia symptoms in individuals with different types of focal dystonia with distinct functional disorders. SIGNIFICANCE: The combined use of these intervention strategies seems to optimize and anticipate satisfactory clinical results in these neurological conditions, characterized by its difficult clinical management.


Assuntos
Distúrbios Distônicos/terapia , Estimulação Transcraniana por Corrente Contínua , Estimulação Magnética Transcraniana , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Técnicas Estereotáxicas , Torcicolo
18.
Acta Neurol Scand ; 142(3): 229-238, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32299120

RESUMO

OBJECTIVE: Individuals with Parkinson's disease (PD) and freezing of gait (FOG) present peripheral and central sensitivity disturbances that impair motor performance. This study aimed to investigate long-term effects of plantar sensory stimulation on brain activity, brain connectivity, and gait velocity of individuals with PD and FOG. METHODS: Twenty-five participants were enrolled in this clinical trial (NCT02594540). Plantar sensory stimulation was delivered using the Automated Mechanical Peripheral Stimulation therapy (AMPS). Volunteers were randomly assigned to real or placebo AMPS groups and received eight sessions of treatment. The primary outcome was brain activity (task-based fMRI-active ankle dorsi-plantar flexion). Secondary outcomes were brain connectivity (resting state-RS fMRI) and gait velocity. fMRI was investigated on the left, right, and mid-sensory motor regions, left and right basal ganglia. RESULTS: No changes in brain activity were observed when task-based fMRI was analyzed. After real AMPS, RS functional connectivity between basal ganglia and sensory-related brain areas increased (insular and somatosensory cortices). Gait velocity also increased after real AMPS. A positive correlation was found between gait velocity and the increased connectivity between sensory, motor and supplementary motor cortices. CONCLUSION: Plantar sensory stimulation through AMPS was not able to modify brain activity. AMPS increased the RS brain connectivity mainly in areas related to sensory processing and sensorimotor integration. Plantar stimulation could be a way to improve plantar sensitivity and consequently ameliorate gait performance. However, the mechanisms behind the way AMPS influences brain pathways are still not completely known.


Assuntos
, Vias Neurais/fisiopatologia , Doença de Parkinson/fisiopatologia , Doença de Parkinson/terapia , Estimulação Física/métodos , Idoso , Idoso de 80 Anos ou mais , Gânglios da Base/fisiopatologia , Método Duplo-Cego , Feminino , Marcha , Transtornos Neurológicos da Marcha/diagnóstico por imagem , Transtornos Neurológicos da Marcha/fisiopatologia , Transtornos Neurológicos da Marcha/terapia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/fisiopatologia , Vias Neurais/diagnóstico por imagem , Doença de Parkinson/diagnóstico por imagem , Resultado do Tratamento
19.
J Stroke Cerebrovasc Dis ; 29(6): 104816, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32321651

RESUMO

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) may promote recovery of motor function after stroke by inducing functional reorganization of cortical circuits. The objective of this study was to examine whether multifocal cortical stimulation using a new wearable transcranial rotating permanent magnet stimulator (TRPMS) can promote recovery of motor function after stroke by inducing functional reorganization of cortical circuits. METHODS: Thirty30 patients with chronic ischemic stroke and stable unilateral weakness were enrolled in a Phase 1/2a randomized double-blind sham-controlled clinical trial to evaluate safety and preliminary efficacy. Bilateral hemispheric stimulation was administered for 20 sessions 40 min each over 4 weeks. The primary efficacy endpoint was the change in functional MRI BOLD activation immediately after end of treatment. Secondary efficacy endpoints were clinical scales of motor function, including the Fugl-Meyer motor arm score, ARAT, grip strength, pinch strength, gait velocity, and NIHSS. RESULTS: TRPMS treatment was well-tolerated with no device-related adverse effects. Active treatment produced a significantly greater increase in the number of active voxels on fMRI than sham treatment (median +48.5 vs -30, p = 0.038). The median active voxel number after active treatment was 8.8-fold greater than after sham (227.5 vs 26, p = 0.016). Although the statistical power was inadequate to establish clinical endpoint benefits, numerical improvements were demonstrated in 5 of 6 clinical scales of motor function. The treatment effects persisted over a 3-month duration of follow-up. CONCLUSIONS: Multifocal bilateral TRPMS was safe and showed significant fMRI changes suggestive of functional reorganization of cortical circuits in patients with chronic ischemic stroke. A larger randomized clinical trial is warranted to verify recovery of motor function.


Assuntos
Isquemia Encefálica/terapia , Atividade Motora , Córtex Motor/fisiopatologia , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Doença Crônica , Avaliação da Deficiência , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Córtex Motor/diagnóstico por imagem , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Texas , Fatores de Tempo , Estimulação Magnética Transcraniana/efeitos adversos , Estimulação Magnética Transcraniana/instrumentação , Resultado do Tratamento , Dispositivos Eletrônicos Vestíveis
20.
Medicine (Baltimore) ; 99(10): e19121, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150052

RESUMO

About 11% to 13% of patients with acute dysphagia induced by stroke remain chronic dysphagia 6 months after stroke which usually leads to many severe complications and poor quality of life.To investigate the effect of transcranial direct current stimulation (tDCS) on swallowing function in the patients with chronic dysphagia after stroke.26 post-stroke patients with chronic dysphagia who received tDCS were identified by electronic medical records between July 2016 and April 2018. Of which, 13 were treated by unilateral hemispheric anodal tDCS at affected pharyngeal motor cortex. 13 eligible patients only treated by conventional therapies but without tDCS were randomly selected by matching on date of admission (±2 weeks) of the patients receiving unilateral tDCS. The swallowing function and quality of life were evaluated before and 2 weeks after treatment.The patients in three groups were comparable. The swallowing function and quality of life of the patients in all the 3 groups had been improved over time. Comparing to the group without tDCS, both the groups with unilateral or bilateral tDCS had shorter oral transit time (1.69 ±â€Š0.95, 0.97 ±â€Š0.71 seconds, respectively) and higher scores of quality of life (159.76 ±â€Š12.59, 179.69 ±â€Š11.81, respectively) after treatment.Both unilateral and bilateral hemispheric anodal tDCS combined with conventional therapies are helpful for recovery of swallowing function in patients with chronic dysphagia induced by stroke, but bilateral anodal tDCS substantially improve more.


Assuntos
Transtornos de Deglutição/terapia , Córtex Motor/fisiopatologia , Reabilitação do Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Estudos de Coortes , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/psicologia , Feminino , Humanos , Masculino , Registros Médicos , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento
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