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1.
Nat Commun ; 12(1): 4399, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285221

RESUMO

The decline of neuronal synapses is an established feature of ageing accompanied by the diminishment of neuronal function, and in the motor system at least, a reduction of behavioural capacity. Here, we have investigated Drosophila motor neuron synaptic terminals during ageing. We observed cumulative fragmentation of presynaptic structures accompanied by diminishment of both evoked and miniature neurotransmission occurring in tandem with reduced motor ability. Through discrete manipulation of each neurotransmission modality, we find that miniature but not evoked neurotransmission is required to maintain presynaptic architecture and that increasing miniature events can both preserve synaptic structures and prolong motor ability during ageing. Our results establish that miniature neurotransmission, formerly viewed as an epiphenomenon, is necessary for the long-term stability of synaptic connections.


Assuntos
Envelhecimento/fisiologia , Neurônios Motores/fisiologia , Terminações Pré-Sinápticas/fisiologia , Transmissão Sináptica/fisiologia , Animais , Animais Geneticamente Modificados , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Potencial Evocado Motor/fisiologia , Masculino , Microscopia Eletrônica , Modelos Animais , Neurônios Motores/ultraestrutura , Músculos/inervação , Músculos/fisiologia , Músculos/ultraestrutura , Terminações Pré-Sinápticas/ultraestrutura , Fatores de Tempo
2.
Clin Neurophysiol ; 132(8): 1770-1776, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34130243

RESUMO

OBJECTIVES: Major Depressive Disorder (MDD) is associated with glutamatergic alterations, including the N-methyl-D-aspartate receptor (NMDA-R). The NMDA-R plays an important role in synaptic plasticity, and individuals with MDD have been shown to have impairments in repetitive Transcranial Magnetic Stimulation (rTMS) motor plasticity. Here, we test whether D-cycloserine, a NMDA-R partial agonist, can rescue TMS motor plasticity in MDD. METHODS: We conducted randomized double-blind placebo-controlled crossover studies in healthy (n = 12) and MDD (n = 12) participants. We stimulated motor cortex using TMS intermittent theta burst stimulation (iTBS) with placebo or D-cycloserine (100 mg). Motor evoked potentials (MEPs) were sampled before and after iTBS. Stimulus response curves (SRC) were characterized at baseline, +90 minutes, and the following day. RESULTS: Acute iTBS MEP facilitation is reduced in MDD and is not rescued by D-cycloserine. After iTBS, SRCs shift to indicate sustained decrease in excitability in healthy participants, yet increased in excitability in MDD participants. D-cycloserine normalized SRC changes from baseline to the following day in MDD participants. In both healthy and MDD participants, D-cycloserine stabilized changes in SRC. CONCLUSION: MDD is associated with alterations in motor plasticity that are rescued and stabilized by NMDA-R agonism. SIGNIFICANCE: Agonism of NMDA receptors rescues iTBS motor plasticity in MDD.


Assuntos
Ciclosserina/uso terapêutico , Transtorno Depressivo Maior/terapia , Córtex Motor/fisiologia , Plasticidade Neuronal/fisiologia , Ritmo Teta/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Estudos Cross-Over , Ciclosserina/farmacologia , Transtorno Depressivo Maior/fisiopatologia , Método Duplo-Cego , Potencial Evocado Motor/efeitos dos fármacos , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Motor/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/agonistas , Receptores de N-Metil-D-Aspartato/fisiologia , Ritmo Teta/efeitos dos fármacos , Adulto Jovem
3.
Nutrients ; 13(5)2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062843

RESUMO

BACKGROUND: Celiac disease (CD) may present or be complicated by neurological and neuropsychiatric manifestations. Transcranial magnetic stimulation (TMS) probes brain excitability non-invasively, also preclinically. We previously demonstrated an intracortical motor disinhibition and hyperfacilitation in de novo CD patients, which revert back after a long-term gluten-free diet (GFD). In this cross-sectional study, we explored the interhemispheric excitability by transcallosal inhibition, which has never been investigated in CD. METHODS: A total of 15 right-handed de novo, neurologically asymptomatic, CD patients and 15 age-matched healthy controls were screened for cognitive and depressive symptoms to the Montreal Cognitive Assessment (MoCA) and the 17-item Hamilton Depression Rating Scale (HDRS), respectively. TMS consisted of resting motor threshold, amplitude, latency, and duration of the motor evoked potentials, duration and latency of the contralateral silent period (cSP). Transcallosal inhibition was evaluated as duration and latency of the ipsilateral silent period (iSP). RESULTS: MoCA and HDRS scored significantly worse in patients. The iSP and cSP were significantly shorter in duration in patients, with a positive correlation between the MoCA and iSP. CONCLUSIONS: An intracortical and interhemispheric motor disinhibition was observed in CD, suggesting the involvement of GABA-mediated cortical and callosal circuitries. Further studies correlating clinical, TMS, and neuroimaging data are needed.


Assuntos
Doença Celíaca/fisiopatologia , Excitabilidade Cortical/fisiologia , Potencial Evocado Motor/fisiologia , Córtex Motor/fisiopatologia , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Estudos de Casos e Controles , Doença Celíaca/terapia , Corpo Caloso/fisiopatologia , Estudos Transversais , Dieta Livre de Glúten , Feminino , Humanos , Inibição Psicológica , Masculino , Pessoa de Meia-Idade , Adulto Jovem
4.
Scand J Med Sci Sports ; 31(9): 1809-1821, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34170574

RESUMO

The etiology of changes in lower-limb neuromuscular function, especially to the central nervous system, may be affected by exercise duration. Direct evidence is lacking as few studies have directly compared different race distances. This study aimed to investigate the etiology of deficits in neuromuscular function following short versus long trail-running races. Thirty-two male trail runners completed one of five trail-running races as LONG (>100 km) or SHORT (<60 km). Pre- and post-race, maximal voluntary contraction (MVC) torque and evoked responses to electrical nerve stimulation during MVCs and at rest were used to assess voluntary activation and muscle contractile properties of knee-extensor (KE) and plantar-flexor (PF) muscles. Transcranial magnetic stimulation (TMS) was used to assess evoked responses and corticospinal excitability in maximal and submaximal KE contractions. Race distance correlated with KE MVC (ρ = -0.556) and twitch (ρ = -0.521) torque decreases (p ≤ .003). KE twitch torque decreased more in LONG (-28 ± 14%) than SHORT (-14 ± 10%, p = .005); however, KE MVC time × distance interaction was not significant (p = .073). No differences between LONG and SHORT for PF MVC or twitch torque were observed. Maximal voluntary activation decreased similarly in LONG and SHORT in both muscle groups (p ≥ .637). TMS-elicited silent period decreased in LONG (p = .021) but not SHORT (p = .912). Greater muscle contractile property impairment in longer races, not central perturbations, contributed to the correlation between KE MVC loss and race distance. Conversely, PF fatigability was unaffected by race distance.


Assuntos
Potencial Evocado Motor/fisiologia , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Corrida/fisiologia , Adulto , Desempenho Atlético/fisiologia , Proteína C-Reativa/análise , Creatina Quinase/sangue , Estimulação Elétrica , Eletromiografia , Nervo Femoral/fisiologia , Humanos , Contagem de Leucócitos , Masculino , Fadiga Muscular/fisiologia , Resistência Física/fisiologia , Nervo Tibial/fisiologia , Fatores de Tempo , Torque , Estimulação Magnética Transcraniana
5.
Clin Neurophysiol ; 132(7): 1499-1504, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34023629

RESUMO

OBJECTIVE: Increased Motor Evoked Potential (MEP) polyphasia was recently described in idiopathic/genetic generalized epilepsy (IGE). Here, we studied the association of MEP polyphasia with treatment response and other clinical characteristics in patients with IGE. METHODS: MEPs were recorded from the biceps brachii, flexor carpi radialis and interosseus dorsalis muscles bilaterally during tonic contraction in IGE patients (n = 72) and historical controls (n = 54) after single pulse transcranial magnetic stimulation. Detailed clinical data was available for all IGE patients; predefined endpoint was the association of MEP polyphasia with treatment response. RESULTS: The mean number of phases was higher in the interosseus dorsalis muscle (2.33 vs. 2.13, p = 0.002) in IGE patients as compared to normal controls, as was the proportion of MEPs with more than two phases in at least one test (59.4% vs. 30%, p < 0.002). MEP polyphasia did not differ between IGE patients and controls in the biceps brachii or the flexor carpi radialis muscles and was not associated with treatment response. Extensive exploratory analyses unveiled fewer phases under valproic acid treatment (p = 0.04) but no additional associations of MEP polyphasia in the interosseous muscle with other clinical characteristics. CONCLUSION: MEP polyphasia is a subclinical symptom of IGE patients but is not associated with treatment response or other routinely assessed clinical characteristics. SIGNIFICANCE: MEP polyphasia is a fixed feature of IGE not modified by clinical variables.


Assuntos
Endofenótipos , Epilepsia Generalizada/diagnóstico , Epilepsia Generalizada/fisiopatologia , Potencial Evocado Motor/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
6.
Clin Neurophysiol ; 132(7): 1462-1480, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34030051

RESUMO

Transcranial magnetic stimulation (TMS) paired with nerve stimulation evokes short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI), which are non-invasive assessments of the excitability of the sensorimotor system. SAI and LAI are abnormally reduced in various special populations in comparison to healthy controls. However, the relationship between afferent inhibition and human behavior remains unclear. The purpose of this review is to survey the current literature and synthesize observations and patterns that affect the interpretation of SAI and LAI in the context of human behavior. We discuss human behaviour across the motor and cognitive domains, and in special and control populations. Further, we discuss future considerations for research in this field and the potential for clinical applications. By understanding how human behavior is mediated by changes in SAI and LAI, this can allow us to better understand the neurophysiological underpinnings of human motor control.


Assuntos
Comportamento/fisiologia , Potencial Evocado Motor/fisiologia , Córtex Motor/fisiologia , Inibição Neural/fisiologia , Plasticidade Neuronal/fisiologia , Estimulação Magnética Transcraniana/métodos , Vias Aferentes/fisiologia , Humanos
7.
Clin Neurophysiol ; 132(7): 1612-1621, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34030058

RESUMO

OBJECTIVE: Navigated transcranial magnetic stimulation (nTMS) is targeted at different cortical sites for diagnostic, therapeutic, and neuroscientific purposes. Correct identification of the cortical target areas is important for achieving desired effects, but it is challenging when no direct responses arise upon target area stimulation. We aimed at utilizing atlas-based marking of cortical areas for nTMS targeting to present a convenient, rater-independent method for overlaying the individual target sites with brain anatomy. METHODS: We developed a pipeline, which fits a brain atlas to the individual brain and enables visualization of the target areas during the nTMS session. We applied the pipeline to our previous nTMS data, focusing on depression and schizophrenia patients. Furthermore, we included examples of Tourette syndrome and tinnitus therapies, as well as neurosurgical and motor mappings. RESULTS: In depression and schizophrenia patients, the visually selected dorsolateral prefrontal cortex (DLPFC) targets were close to the border between atlas areas A9/46 and A8. In the other areas, the atlas-based areas were in agreement with the treatment targets. CONCLUSIONS: The atlas-based target areas agreed well with the cortical targets selected by experts during the treatments. SIGNIFICANCE: Overlaying atlas information over the navigation view is a convenient and useful add-on for improving nTMS targeting.


Assuntos
Atlas como Assunto , Biologia Computacional/métodos , Imageamento por Ressonância Magnética/métodos , Neuronavegação/métodos , Córtex Pré-Frontal/diagnóstico por imagem , Estimulação Magnética Transcraniana/métodos , Adolescente , Adulto , Idoso , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/fisiologia , Adulto Jovem
8.
Clin Neurophysiol ; 132(7): 1647-1662, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34030059

RESUMO

OBJECTIVE: To test whether change in motor evoked potential (ΔMEP) induced by continuous theta-burst stimulation (cTBS) of motor cortex (M1) distinguishes adults with autism spectrum disorder (ASD) from neurotypicals, and to explore the contribution of two common polymorphisms related to neuroplasticity. METHODS: 44 adult neurotypical (NT) participants (age 21-65, 34 males) and 19 adults with ASD (age 21-58, 17 males) prospectively underwent M1 cTBS. Their data were combined with previously obtained results from 35 NT and 35 ASD adults. RESULTS: ΔMEP at 15 minutes post-cTBS (T15) was a significant predictor of diagnosis (p = 0.04) in the present sample (n=63). T15 remained a significant predictor in a larger sample (n=91) and when partially imputed based on T10-T20 from a yet-greater sample (N=133). T15 also remained a significant predictor of diagnosis among brain-derived neurotrophic factor (BDNF) Met+ and apolipoprotein E (APOE) ε4- subjects (p's < 0.05), but not among Met- or ε4+ subjects (p's > 0.19). CONCLUSIONS: ΔMEP at T15 post-cTBS is a significant biomarker for adults with ASD, and its utility is modulated by BDNF and APOE polymorphisms. SIGNIFICANCE: M1 cTBS response is a physiologic biomarker for adults with ASD in large samples, and controlling for BDNF and APOE polymorphisms can improve its diagnostic utility.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/fisiopatologia , Excitabilidade Cortical/fisiologia , Potencial Evocado Motor/fisiologia , Córtex Motor/fisiopatologia , Ritmo Teta/fisiologia , Adulto , Idoso , Transtorno do Espectro Autista/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Adulto Jovem
9.
Best Pract Res Clin Anaesthesiol ; 35(2): 221-229, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34030806

RESUMO

Dexmedetomidine can be used for sedation and analgesia and has been approved for this use by the European Medicines Agency since 2017. It causes an arousable state of sedation, which is beneficial during neurosurgical procedures that require the patient to cooperate with neurological tests (i.e. tumor surgery or implantation of deep brain stimulators). During procedures where monitoring of somatosensory evoked potentials and/or motor evoked potentials is required, dexmedetomidine can be used as an adjunct to general anesthesia with GABAergic drugs to decrease the dose of the latter when these drugs impair the monitoring signals. The use of dexmedetomidine has also been associated with neuroprotective effects and a decreased incidence of delirium, but studies confirming these effects in the peri-operative (neuro-)surgical setting are lacking. Although dexmedetomidine does not cause respiratory depression, its hemodynamic effects are complex and careful patient selection, choice of dose, and monitoring must be performed.


Assuntos
Dexmedetomidina/administração & dosagem , Potencial Evocado Motor/efeitos dos fármacos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Hipnóticos e Sedativos/administração & dosagem , Procedimentos Neurocirúrgicos/métodos , Dexmedetomidina/efeitos adversos , Potencial Evocado Motor/fisiologia , Potenciais Somatossensoriais Evocados/fisiologia , Humanos , Insuficiência Respiratória/induzido quimicamente , Insuficiência Respiratória/fisiopatologia , Insuficiência Respiratória/prevenção & controle
10.
J Clin Neurophysiol ; 38(3): 166-170, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33958566

RESUMO

SUMMARY: Motor-evoked potentials (MEPs) can be used to assess the integrity of the descending corticospinal tract in the laboratory. Evoked potentials (EPs) have been widely used in the past for the diagnosis of multiple sclerosis (MS), but they are now becoming more useful in assessing the prognosis of the disease. Motor-evoked potentials have been included in EP scales that have demonstrated good correlations with clinical disability. Soon after the onset of MS, it is possible to detect an ongoing process of neurodegeneration and axonal loss. Axonal loss is probably responsible for the disability and disease progression that occurs in MS. Given the good correlations of EPs in detecting disease progression in MS, they have been used to monitor the effects of drugs used to treat the disease. Several clinical trials used MEPs as part of their EP evaluation, but MEPs have never been used as a measure of efficacy in clinical trials testing neuroprotective agents, although MEPs could be a very promising tool to measure neuroprotection and remyelination resulting from these drugs. To be used in multicenter clinical trials, MEP readings should be comparable between centers. Standardized multicenter EP assessment with central reading has been demonstrated to be feasible and reliable. Although MEP measurements have been correlated with clinical scores and other measures of neurodegeneration, further validation of MEP amplitude measurements is needed regarding their validity, reliability, and sensitivity before they can be routinely used in clinical drug trials in MS.


Assuntos
Potencial Evocado Motor/fisiologia , Esclerose Múltipla , Adulto , Ensaios Clínicos como Assunto , Progressão da Doença , Fenômenos Eletrofisiológicos , Eletrofisiologia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/diagnóstico , Esclerose Múltipla/fisiopatologia , Tratos Piramidais/fisiopatologia , Reprodutibilidade dos Testes
11.
Muscle Nerve ; 64(2): 215-219, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34008857

RESUMO

INTRODUCTION/AIMS: Cortical hyperexcitability is a feature of amyotrophic lateral sclerosis (ALS) and cortical excitability can be measured using transcranial magnetic stimulation (TMS). Resting motor threshold (MT) is a measure of cortical excitability, largely driven by glutamate. Perampanel, a glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor blocker, is predicted to increase the cortical excitability threshold. This study aimed to evaluate TMS to functionally assess target engagement in a study of perampanel in ALS. METHOD: We studied the MT of ALS patients randomized to a single dose of perampanel or placebo 5:1 hourly for 4 h. Twelve patients participated at 4 mg and 7 returned for dosing and retesting at 8 mg. The study was terminated in April 2020 due to coronavirus disease 2019-related restrictions, after 7 out of 12 planned patients had received the 8 mg dose. Serum concentrations were also measured. RESULTS: Ten patients received the 4 mg dose (2 received placebo) and 5 received the 8 mg dose (2 received placebo). Motor Threshold increased at 2 h after dosing in the combined treatment group +7% of maximal stimulator output (P < .01). Change could be detected in the larger 4 mg group (P = .02), but not in the smaller 8 mg dose group (P = .1). No side effects were reported after single dose exposure. DISCUSSION: This study shows that perampanel effects the physiology of upper motor neurons. Studies aiming at gauging the effect of perampanel on ALS disease progression are already ongoing. Motor threshold may serve as a marker of biological target engagement.


Assuntos
Esclerose Amiotrófica Lateral/tratamento farmacológico , Excitabilidade Cortical/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Piridonas/administração & dosagem , Receptores de AMPA/antagonistas & inibidores , Idoso , Esclerose Amiotrófica Lateral/sangue , Esclerose Amiotrófica Lateral/diagnóstico , Excitabilidade Cortical/fisiologia , Método Duplo-Cego , Potencial Evocado Motor/efeitos dos fármacos , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios Motores/fisiologia , Projetos Piloto , Piridonas/sangue , Receptores de AMPA/fisiologia , Estimulação Magnética Transcraniana/métodos
12.
J Neuroeng Rehabil ; 18(1): 76, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33957937

RESUMO

BACKGROUND: A novel electromechanical robotic-exoskeleton was designed in-house for the rehabilitation of wrist joint and Metacarpophalangeal (MCP) joint. OBJECTIVE: The objective was to compare the rehabilitation effectiveness (clinical-scales and neurophysiological-measures) of robotic-therapy training sessions with dose-matched conventional therapy in patients with stroke. METHODS: A pilot prospective parallel randomized controlled study at clinical settings was designed for patients with stroke within 2 years of chronicity. Patients were randomly assigned to receive an intervention of 20 sessions of 45 min each, five days a week for four weeks, in Robotic-therapy Group (RG) (n = 12) and conventional upper-limb rehabilitation in Control-Group (CG) (n = 11). We intended to evaluate the effects of a novel exoskeleton based therapy on the functional rehabilitation outcomes of upper-limb and cortical-excitability in patients with stroke as compared to the conventional-rehabilitation. Clinical-scales- Modified Ashworth Scale, Active Range of Motion, Barthel-Index, Brunnstrom-stage and Fugl-Meyer (FM) scale and neurophysiological measures of cortical-excitability (using Transcranial Magnetic Stimulation) -Motor Evoked Potential and Resting Motor threshold, were acquired pre- and post-therapy. RESULTS: No side effects were noticed in any of the patients. Both RG and CG showed significant (p < 0.05) improvement in all clinical motor-outcomes except Modified Ashworth Scale in CG. RG showed significantly (p < 0.05) higher improvement over CG in Modified Ashworth Scale, Active Range of Motion and Fugl-Meyer scale and FM Wrist-/Hand component. An increase in cortical-excitability in ipsilesional-hemisphere was found to be statistically significant (p < 0.05) in RG over CG, as indexed by a decrease in Resting Motor Threshold and increase in the amplitude of Motor Evoked Potential. No significant changes were shown by the contralesional-hemisphere. Interhemispheric RMT-asymmetry evidenced significant (p < 0.05) changes in RG over CG indicating increased cortical-excitability in ipsilesional-hemisphere along with interhemispheric changes. CONCLUSION: Robotic-exoskeleton training showed improvement in motor outcomes and cortical-excitability in patients with stroke. Neurophysiological changes in RG could most likely be a consequence of plastic reorganization and use-dependent plasticity. Trial registry number: ISRCTN95291802.


Assuntos
Potencial Evocado Motor/fisiologia , Exoesqueleto Energizado , Córtex Motor/fisiopatologia , Plasticidade Neuronal/fisiologia , Reabilitação do Acidente Vascular Cerebral , Adulto , Idoso , Feminino , Mãos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Modalidades de Fisioterapia , Estudos Prospectivos , Robótica/instrumentação , Robótica/métodos , Acidente Vascular Cerebral/fisiopatologia , Reabilitação do Acidente Vascular Cerebral/instrumentação , Reabilitação do Acidente Vascular Cerebral/métodos , Estimulação Magnética Transcraniana , Resultado do Tratamento , Punho/fisiopatologia
13.
J Neuroeng Rehabil ; 18(1): 89, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-34039346

RESUMO

BACKGROUND: Cerebellar electrical stimulation has shown promise in improving motor recovery post-stroke in both rodent and human studies. Past studies have used motor evoked potentials (MEPs) to evaluate how cerebellar stimulation modulates ongoing activity in the cortex, but the underlying mechanisms are incompletely understood. Here we used invasive electrophysiological recordings from the intact and stroke-injured rodent primary motor cortex (M1) to assess how epidural cerebellar stimulation modulates neural dynamics at the level of single neurons as well as at the level of mesoscale dynamics. METHODS: We recorded single unit spiking and local field potentials (LFPs) in both the intact and acutely stroke-injured M1 contralateral to the stimulated cerebellum in adult Long-Evans rats under anesthesia. We analyzed changes in the firing rates of single units, the extent of synchronous spiking and power spectral density (PSD) changes in LFPs during and post-stimulation. RESULTS: Our results show that post-stimulation, the firing rates of a majority of M1 neurons changed significantly with respect to their baseline rates. These firing rate changes were diverse in character, as the firing rate of some neurons increased while others decreased. Additionally, these changes started to set in during stimulation. Furthermore, cross-correlation analysis showed a significant increase in coincident firing amongst neuronal pairs. Interestingly, this increase in synchrony was unrelated to the direction of firing rate change. We also found that neuronal ensembles derived through principal component analysis were more active post-stimulation. Lastly, these changes occurred without a significant change in the overall spectral power of LFPs post-stimulation. CONCLUSIONS: Our results show that cerebellar stimulation caused significant, long-lasting changes in the activity patterns of M1 neurons by altering firing rates, boosting neural synchrony and increasing neuronal assemblies' activation strength. Our study provides evidence that cerebellar stimulation can directly modulate cortical dynamics. Since these results are present in the perilesional cortex, our data might also help explain the facilitatory effects of cerebellar stimulation post-stroke.


Assuntos
Cerebelo/fisiopatologia , Estimulação Elétrica/métodos , Neurônios/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Eletrocorticografia , Potencial Evocado Motor/fisiologia , Masculino , Ratos , Ratos Long-Evans
14.
Spine (Phila Pa 1976) ; 46(12): E694-E700, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34027929

RESUMO

STUDY DESIGN: Prospective multicenter observational study. OBJECTIVE: To evaluate transcranial motor-evoked potentials (Tc-MEPs) baseline characteristics of lower limb muscles and to determine the accuracy of Tc-MEPs monitoring based on preoperative motor status in surgery for high-risk spinal disease. SUMMARY OF BACKGROUND DATA: Neurological complications are potentially serious side effects in surgery for high-risk spine disease. Intraoperative spinal neuromonitoring (IONM) using Tc-MEPs waveforms can be used to identify neurologic deterioration, but cases with preoperative motor deficit tend to have poor waveform derivation. METHODS: IONM was performed using Tc-MEPs for 949 patients in high-risk spinal surgery. A total of 4454 muscles in the lower extremities were chosen for monitoring. The baseline Tc-MEPs was recorded immediately after exposure of the spine. The derivation rate was defined as muscles detected/muscles prepared for monitoring. A preoperative neurological grade was assigned using the manual muscle test (MMT) score. RESULTS: The 949 patients (mean age 52.5 ±â€Š23.3 yrs, 409 males [43%]) had cervical, thoracic, thoracolumbar, and lumbar lesions at rates of 32%, 40%, 26%, and 13%, respectively. Preoperative severe motor deficit (MMT ≤3) was present in 105 patients (11%), and thoracic ossification of the posterior longitudinal ligament (OPLL) was the most common disease in these patients. There were 32 patients (3%) with no detectable waveform in any muscles, and these cases had mostly thoracic lesions. Baseline Tc-MEPs responses were obtained from 3653/4454 muscles (82%). Specificity was significantly lower in the severe motor deficit group. Distal muscles had a higher waveform derivation rate, and the abductor hallucis (AH) muscle had the highest derivation rate, including in cases with preoperative severe motor deficit. CONCLUSION: In high-risk spinal surgery, Tc-MEPs collected with multi-channel monitoring had significantly lower specificity in cases with preoperative severe motor deficit. Distal muscles had a higher waveform derivation rate and the AH muscle had the highest rate, regardless of the severity of motor deficit preoperatively.Level of Evidence: 3.


Assuntos
Potencial Evocado Motor/fisiologia , Monitorização Neurofisiológica Intraoperatória , Doenças da Coluna Vertebral/cirurgia , Adulto , Idoso , Feminino , Humanos , Extremidade Inferior/inervação , Extremidade Inferior/fisiologia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Período Pré-Operatório , Estudos Prospectivos
15.
Clin Neurophysiol ; 132(6): 1195-1199, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33895054

RESUMO

OBJECTIVE: The intraoperative monitoring of cranial nerve function records evoked responses at latencies of a few milliseconds. Unfortunately, these responses may be masked by the electrical artifact of the stimulation pulse. In electrical stimulation, the return discharge of the stimulation pulse significantly contributes to the width of the electrical artifact. METHODS: We have generated stimulation pulses with an ISIS Neurostimulator (inomed Medizintechnik GmbH) providing a novel stimulation artifact reduction technique. It delays the return discharge of the stimulating pulse beyond the latency of the expected physiological response. This delayed return discharge is controlled such that no unintended physiological response is evoked. RESULTS: In 21 neurosurgical interventions with motor evoked potentials of the facial nerve (FNMEP), the stimulation method generated a stimulation pulse artifact with reduced tail duration. Compared to conventional stimulation with immediate return discharge, the signal-to-noise ratio of the physiological response may improve with the novel stimulation method. In some surgeries, only the novel stimulation method generated clearly identifiable response signals. CONCLUSIONS: The reduced width of the stimulation artifact extends the toolbox of intraoperative monitoring modalities by rendering the interpretation of cranial nerve evoked potentials more reliable. SIGNIFICANCE: The novel technique enhances the number of patients for whom intraoperative monitoring may aid in cranial neurosurgery.


Assuntos
Potencial Evocado Motor/fisiologia , Nervo Facial/fisiologia , Adulto , Idoso , Estimulação Elétrica , Eletromiografia , Feminino , Humanos , Monitorização Neurofisiológica Intraoperatória , Masculino , Pessoa de Meia-Idade
16.
Sci Rep ; 11(1): 6322, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737659

RESUMO

During voluntary contractions, corticomuscular coherence (CMC) is thought to reflect a mutual interaction between cortical and muscle oscillatory activities, respectively measured by electroencephalography (EEG) and electromyography (EMG). However, it remains unclear whether CMC modulation would depend on the contribution of neural mechanisms acting at the spinal level. To this purpose, modulations of CMC were compared during submaximal isometric, shortening and lengthening contractions of the soleus (SOL) and the medial gastrocnemius (MG) with a concurrent analysis of changes in spinal excitability that may be reduced during lengthening contractions. Submaximal contractions intensity was set at 50% of the maximal SOL EMG activity. CMC was computed in the time-frequency domain between the Cz EEG electrode signal and the unrectified SOL or MG EMG signal. Spinal excitability was quantified through normalized Hoffmann (H) reflex amplitude. The results indicate that beta-band CMC and normalized H-reflex were significantly lower in SOL during lengthening compared with isometric contractions, but were similar in MG for all three muscle contraction types. Collectively, these results highlight an effect of contraction type on beta-band CMC, although it may differ between agonist synergist muscles. These novel findings also provide new evidence that beta-band CMC modulation may involve spinal regulatory mechanisms.


Assuntos
Córtex Motor/fisiologia , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Medula Espinal/fisiologia , Adulto , Estimulação Elétrica , Eletroencefalografia , Eletromiografia , Potencial Evocado Motor/fisiologia , Potencial Evocado Motor/efeitos da radiação , Feminino , Reflexo H/fisiologia , Reflexo H/efeitos da radiação , Humanos , Contração Isométrica/fisiologia , Contração Isométrica/efeitos da radiação , Masculino , Córtex Motor/diagnóstico por imagem , Córtex Motor/efeitos da radiação , Contração Muscular/efeitos da radiação , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/efeitos da radiação , Torque
17.
Exp Neurol ; 340: 113679, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33662380

RESUMO

The receptor-type protein tyrosine phosphatase sigma (PTPRσ) regulates axonal regeneration/sprouting as a molecular switch in response to glycan ligands. Cell surface heparan sulfate oligomerizes PTPRσ and inactivates its enzymatic activity, which in turn promotes axonal growth. In contrast, matrix-associated chondroitin sulfate monomerizes PTPRσ and activates it. This leads to dephosphorylation of its specific substrates, such as cortactin, resulting in a failure of axonal regeneration after injury. However, this molecular switch model has never been challenged in a clinical situation. In this study, we demonstrated that enoxaparin, a globally approved anticoagulant consisting of heparin oligosaccharides with an average molecular weight of 45 kDa, induced clustering and inactivated PTPRσ in vitro. Enoxaparin induced PTPRσ clustering, and counteracted PTPRσ-mediated dephosphorylation of cortactin, which was shown to be important for inhibition of axonal regeneration. Systemic administration of enoxaparin promoted anatomical recovery after both optic nerve and spinal cord injuries in rats at clinically tolerated doses. Moreover, enoxaparin promoted recovery of motor function without obvious hemorrhage. Collectively, our data provide a new strategy for the treatment of traumatic axonal injury.


Assuntos
Anticoagulantes/uso terapêutico , Enoxaparina/uso terapêutico , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/antagonistas & inibidores , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Anticoagulantes/farmacologia , Enoxaparina/farmacologia , Potencial Evocado Motor/efeitos dos fármacos , Potencial Evocado Motor/fisiologia , Feminino , Células HEK293 , Humanos , Ratos , Ratos Sprague-Dawley , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Recuperação de Função Fisiológica/fisiologia , Traumatismos da Medula Espinal/metabolismo , Vértebras Torácicas/lesões
18.
Bone Joint J ; 103-B(3): 547-552, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33641421

RESUMO

AIMS: Spinal deformity surgery carries the risk of neurological injury. Neurophysiological monitoring allows early identification of intraoperative cord injury which enables early intervention resulting in a better prognosis. Although multimodal monitoring is the ideal, resource constraints make surgeon-directed intraoperative transcranial motor evoked potential (TcMEP) monitoring a useful compromise. Our experience using surgeon-directed TcMEP is presented in terms of viability, safety, and efficacy. METHODS: We carried out a retrospective review of a single surgeon's prospectively maintained database of cases in which TcMEP monitoring had been used between 2010 and 2017. The upper limbs were used as the control. A true alert was recorded when there was a 50% or more loss of amplitude from the lower limbs with maintained upper limb signals. Patients with true alerts were identified and their case history analyzed. RESULTS: Of the 299 cases reviewed, 279 (93.3%) had acceptable traces throughout and awoke with normal clinical neurological function. No patient with normal traces had a postoperative clinical neurological deficit. True alerts occurred in 20 cases (6.7%). The diagnoses of the alert group included nine cases of adolescent idiopathic scoliosis (AIS) (45%) and six of congenital scoliosis (30%). The incidence of deterioration based on diagnosis was 9/153 (6%) for AIS, 6/30 (20%) for congenital scoliosis, and 2/16 (12.5%) for spinal tuberculosis. Deterioration was much more common in congenital scoliosis than in AIS (p = 0.020). Overall, 65% of alerts occurred during rod instrumentation: 15% occurred during decompression of the internal apex in vertebral column resection surgery. Four alert cases (20%) awoke with clinically detectable neurological compromise. CONCLUSION: Surgeon-directed TcMEP monitoring has a 100% negative predictive value and allows early identification of physiological cord distress, thereby enabling immediate intervention. In resource constrained environments, surgeon-directed TcMEP is a viable and effective method of intraoperative spinal cord monitoring. Level of evidence: III Cite this article: Bone Joint J 2021;103-B(3):547-552.


Assuntos
Potencial Evocado Motor/fisiologia , Monitorização Neurofisiológica Intraoperatória/métodos , Procedimentos Neurocirúrgicos , Traumatismos da Medula Espinal/prevenção & controle , Doenças da Coluna Vertebral/cirurgia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos
19.
J Back Musculoskelet Rehabil ; 34(4): 631-637, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33646142

RESUMO

BACKGROUND: Rotator cuff muscles are structurally and functionally different from other upper-limb muscles because they are responsible for glenohumeral joint stability. Neuromuscular electrical stimulation (NMES) induces excitability changes (increase or decrease) of the corticospinal tract (CST) in the peripheral muscles, such as those of the finger. However, it remains unclear whether similar results are obtained when targeting the infraspinatus muscle, which has properties that differ from other muscles, in healthy subjects. OBJECTIVE: We investigated the immediate effects of NMES on the corticospinal excitability of the infraspinatus muscle, a rotator cuff muscle, in healthy subjects. METHODS: Thirteen healthy right-handed men (mean age: 26.77 ± 2.08 years) participated in this study. The motor evoked potentials (MEPs) and the maximum compound muscle action potential (Mmax) were recorded before NMES to the right infraspinatus and within 15 minutes after the end of the NMES. RESULTS: NMES on the infraspinatus muscle significantly increased its MEP amplitude (Pre: 0.45 mV [0.33-0.48]; Post: 0.54 mV [0.46-0.60] (median [lower quartile to higher quartile]); p= 0.005) but had no effect on Mmax (Pre: 2.95 mV [2.59-4.71]; Post: 3.35 mV [2.76-4.72]; p= 0.753). CONCLUSIONS: NMES application to the infraspinatus muscle increases CST excitability without producing immediate changes in the neuromuscular junction or muscle hypertrophy.


Assuntos
Potencial Evocado Motor/fisiologia , Músculo Esquelético/fisiologia , Tratos Piramidais/fisiologia , Manguito Rotador/fisiologia , Potenciais de Ação/fisiologia , Adulto , Estimulação Elétrica/métodos , Eletromiografia , Humanos , Masculino , Adulto Jovem
20.
J Neurosci ; 41(14): 3163-3179, 2021 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-33653698

RESUMO

The primary motor cortex hand area (M1HAND) and adjacent dorsal premotor cortex (PMd) form the so-called motor hand knob in the precentral gyrus. M1HAND and PMd are critical for dexterous hand use and are densely interconnected via corticocortical axons, lacking a sharp demarcating border. In 24 young right-handed volunteers, we performed multimodal mapping to delineate the relationship between structure and function in the right motor hand knob. Quantitative structural magnetic resonance imaging (MRI) at 3 tesla yielded regional R1 maps as a proxy of cortical myelin content. Participants also underwent functional MRI (fMRI). We mapped task-related activation and temporal precision, while they performed a visuomotor synchronization task requiring visually cued abduction movements with the left index or little finger. We also performed sulcus-aligned transcranial magnetic stimulation of the motor hand knob to localize the optimal site (hotspot) for evoking a motor evoked potential (MEP) in two intrinsic hand muscles. Individual motor hotspot locations varied along the rostrocaudal axis. The more rostral the motor hotspot location in the precentral crown, the longer were corticomotor MEP latencies. "Hotspot rostrality" was associated with the regional myelin content in the precentral hand knob. Cortical myelin content also correlated positively with task-related activation of the precentral crown and temporal precision during the visuomotor synchronization task. Together, our results suggest a link among cortical myelination, the spatial cortical representation, and temporal precision of finger movements. We hypothesize that the myelination of cortical axons facilitates neuronal integration in PMd and M1HAND and, hereby, promotes the precise timing of movements.SIGNIFICANCE STATEMENT Here we used magnetic resonance imaging and transcranial magnetic stimulation of the precentral motor hand knob to test for a link among cortical myelin content, functional corticomotor representations, and manual motor control. A higher myelin content of the precentral motor hand knob was associated with more rostral corticomotor presentations, with stronger task-related activation and a higher precision of movement timing during a visuomotor synchronization task. We propose that a high precentral myelin content enables fast and precise neuronal integration in M1 (primary motor cortex) and dorsal premotor cortex, resulting in higher temporal precision during dexterous hand use. Our results identify the degree of myelination as an important structural feature of the neocortex that is tightly linked to the function and behavior supported by the cortical area.


Assuntos
Mapeamento Encefálico/métodos , Dedos/fisiologia , Individualidade , Córtex Motor/fisiologia , Bainha de Mielina/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Potencial Evocado Motor/fisiologia , Feminino , Mãos/fisiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Córtex Motor/diagnóstico por imagem , Estimulação Magnética Transcraniana/métodos , Adulto Jovem
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