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This publisher's note contains a correction to [Opt. Express30, 28805 (2022)10.1364/OE.462775].
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Microscale 3D printing technologies have been of increasing interest in industry and research for several years. Unfortunately, the fabricated structures always deviate from the respective expectations, often caused by the physico-chemical properties during and after the printing process. Here, we show first steps towards a simple, fast and easy to implement algorithm to predict the final structure topography for multi-photon lithography - also known as Direct Laser Writing (DLW). The three main steps of DLW, (i) exposure of a photo resin, (ii) cross-linking of the resin, and (iii) subsequent shrinkage are approximated by mathematical operations, showing promising results in coincidence with experimental observations. For example, the root-mean-square error (rmse) between the unmodified 3D print of a radial-symmetrically chirped topography and our predicted topography is only 0.46 µm, whereas the rmse between this 3D print and its target is 1.49 µm. Thus, our robust predictions can be used prior to the printing process to minimize undesired deviations between the target structure and the final 3D printed structure. Using a Downhill-Simplex algorithm for identifying the optimal prediction parameters, we were able to reduce the rmse from 4.04 µm to 0.33 µm by only two correction loops in our best-case scenario (rmse = 0.72 µm after one loop). Consequently, this approach can eliminate the need for many structural optimization loops to produce highly conformal and high quality micro structures in the future.
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We present I=1/2 D^{*}π scattering amplitudes from lattice QCD and determine two low-lying J^{P}=1^{+} axial-vector D_{1} states and a J^{P}=2^{+} tensor D_{2}^{*}. Computing finite-volume spectra at a light-quark mass corresponding to m_{π}≈391 MeV, for the first time, we are able to constrain coupled J^{P}=1^{+} D^{*}π amplitudes with ^{2S+1}â_{J}=^{3}S_{1} and ^{3}D_{1} as well as coupled J^{P}=2^{+} Dπ(^{1}D_{2}} and D^{*}π(^{3}D_{2}} amplitudes via Lüscher's quantization condition. Analyzing the scattering amplitudes for poles we find a near-threshold bound state, producing a broad feature in D^{*}π{^{3}S_{1}}. A narrow bump occurs in D^{*}π{^{3}D_{1}} due to a D_{1} resonance. A single resonance is found in J^{P}=2^{+} coupled to Dπ and D^{*}π. A relatively low mass and large coupling are found for the lightest D_{1}, suggestive of a state that will evolve into a broad resonance as the light-quark mass is reduced. An earlier calculation of the scalar D_{0}^{*} using the same light-quark mass enables comparisons to the heavy-quark limit.
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OBJECTIVE: To investigate the initial termination rate of status epilepticus (SE) in a large observational study and explore associated variables. METHODS: Data of adults treated for SE were collected prospectively in centers in Germany, Austria, and Switzerland, during 4.5 years. Incident episodes of 1,049 patients were analyzed using uni- and multivariate statistics to determine factors predicting cessation of SE within 1 hour (for generalized convulsive SE [GCSE]) and 12 hours (for non-GCSE) of initiating treatment. RESULTS: Median age at SE onset was 70 years; most frequent etiologies were remote (32%) and acute (31%). GCSE was documented in 43%. Median latency between SE onset and first treatment was 30 minutes in GCSE and 150 minutes in non-GCSE. The first intravenous compound was a benzodiazepine in 86% in GCSE and 73% in non-GCSE. Bolus doses of the first treatment step were lower than recommended by current guidelines in 76% of GCSE patients and 78% of non-GCSE patients. In 319 GCSE patients (70%), SE was ongoing 1 hour after initiating treatment and in 342 non-GCSE patients (58%) 12 hours after initiating treatment. Multivariate Cox regression demonstrated that use of benzodiazepines as first treatment step and a higher cumulative dose of anticonvulsants within the first period of treatment were associated with shorter time to cessation of SE for both groups. INTERPRETATION: In clinical practice, treatment guidelines were not followed in a substantial proportion of patients. This underdosing correlated with lack of cessation of SE. Our data suggest that sufficiently dosed benzodiazepines should be used as a first treatment step. ANN NEUROL 2019;85:421-432.
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Anticonvulsivantes/uso terapêutico , Benzodiazepinas/uso terapêutico , Estado Epiléptico/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Relação Dose-Resposta a Droga , Feminino , Alemanha , Fidelidade a Diretrizes , Humanos , Levetiracetam/uso terapêutico , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Guias de Prática Clínica como Assunto , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Sistema de Registros , Suíça , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Status epilepticus (SE) is an important neurological emergency lacking adequate evidence for efficacy and safety of treatment beyond the application of benzodiazepines as first treatment step. To bridge the gap between the few pivotal trials and retrospective uncontrolled case series, we established a prospective multicenter registry recruiting patients in experienced centers in German-speaking countries. We could document 1179 episodes of 1049 patients over a period of 5â¯years. First data analysis showed that in the majority of the episodes, established treatment guidelines were not followed. Latency between status onset and different treatment steps were longer, and bolus doses lower than recommended. Moreover, a relevant proportion of the patients did not receive a benzodiazepine but levetiracetam as first treatment step. Although SE could be controlled in more than 90% of the episodes, lower bolus dose and longer treatment latency were associated with refractoriness of the SE in multivariate analysis. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.
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Anticonvulsivantes/uso terapêutico , Estado Epiléptico/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/efeitos adversos , Áustria , Benzodiazepinas/administração & dosagem , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Feminino , Alemanha , Humanos , Levetiracetam/administração & dosagem , Levetiracetam/efeitos adversos , Levetiracetam/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sistema de Registros , Estado Epiléptico/tratamento farmacológico , Suíça , Adulto JovemRESUMO
Evidence is scarce regarding the treatment of status epilepticus (SE). Only a few large randomized controlled trials have been published. Therefore, we set up a multicenter registry to prospectively document treatment practice in several different large hospitals in German-speaking countries. Over a period of more than 4 years, we were able to document 1179 episodes of 1049 patients who were treated for SE in 1 of the 8 participating centers in Germany, Austria, and Switzerland. Median age was 70 years. The most frequent etiology was remote (32%), followed by acute (31%), or a mixture of acute and remote factors (10%). Semiology was generalized convulsive in 44%, focal motor in 27%, and nonconvulsive in 30%. Only a few patients did not have relevant comorbidities. Median latency between SE onset and first treatment was 1 hour (median). Three hundred ninety-three (32%) of the patients were treated within 30 minutes after onset. The first treatment step consisted of benzodiazepines in more than 80%, and in levetiracetam in 15%. Five hundred eleven patients (49%) were refractory (defined as ongoing SE after application of benzodiazepine and 1 intravenous anticonvulsant). Further analysis of these registry data may be important for hypothesis generation and trial design for treatment of status epilepticus.
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Anticonvulsivantes/uso terapêutico , Sistema de Registros , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria , Estudos de Coortes , Feminino , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
BACKGROUND: Evidence regarding the different treatment options of status epilepticus (SE) in adults is scarce. Large randomized trials cover only one treatment at early stage and suggest the superiority of benzodiazepines over placebo, of intravenous lorazepam over intravenous diazepam or over intravenous phenytoin alone, and of intramuscular midazolam over intravenous lorazepam. However, many patients will not be treated successfully with the first treatment step. A large randomized trial covering the treatment of established status (ESETT) has just been funded recently by the NIH and will not start before 2015, with expected results in 2018; a trial on the treatment of refractory status with general anesthetics was terminated early due to insufficient recruitment. Therefore, a prospective multicenter observational registry was set up; this may help in clinical decision-making until results from randomized trials are available. METHODS/DESIGN: SENSE is a prospective, multicenter registry for patients treated for SE. The primary objective is to document patient characteristics, treatment modalities and in-house outcome of consecutive adults admitted for SE treatment in each of the participating centres and to identify predictors of outcome. Pre-treatment, treatment-related and outcome variables are documented systematically. To allow for meaningful multivariate analysis in the patient subgroups with refractory SE, a cohort size of 1000 patients is targeted. DISCUSSION: The results of the study will provide information about risks and benefits of specific treatment steps in different patient groups with SE at different points of time. Thus, it will support clinical decision-making and, furthermore, it will be helpful in the planning of treatment trials. TRIAL REGISTRATION: DRKS00000725.
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Anticonvulsivantes/uso terapêutico , Sistema de Registros , Estado Epiléptico/tratamento farmacológico , Adulto , Idoso , Diazepam/uso terapêutico , Feminino , Humanos , Lorazepam/uso terapêutico , Masculino , Midazolam/uso terapêutico , Pessoa de Meia-Idade , Fenitoína/uso terapêutico , Estudos ProspectivosRESUMO
Nicotine improves cognitive functions by modulating neuroplasticity and cortical excitability in nonsmoking subjects. As shown recently, the positive effect of nicotine on cognition might at least partially be caused by a focusing effect of nicotine on neuroplasticity in these subjects. Concordant to this, smokers under nicotine withdrawal show reduced cognitive abilities, which are at least partially restituted by nicotine consumption. We aimed to explore the neurophysiological foundation of these effects by exploring nonfocal and focal plasticity-inducing protocols in human smokers under nicotine withdrawal and exposition. Focal, synapse-specific plasticity was induced by paired associative stimulation (PAS), while nonfocal plasticity was induced by transcranial direct current stimulation (tDCS). Each subject (12) received placebo and nicotine patches combined with one of the stimulation protocols to the primary motor cortex. Corticospinal excitability was monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. In smokers during nicotine withdrawal, facilitatory plasticity induced by tDCS and PAS was abolished, but restituted by nicotine. In contrast, excitability-diminishing plasticity was not affected by nicotine withdrawal. Under nicotine, the inhibitory aftereffects of PAS were delayed and prolonged, while the tDCS-generated excitability reduction was abolished. Thus, absent facilitatory plasticity in smokers during nicotine withdrawal is restituted by nicotine, favoring the deficit-compensating hypothesis of nicotine consumption. These results might shed further light on the proposed mechanism of nicotine on cognition and attention, which might be connected to nicotine addiction and probability of relapse in smokers.
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Potencial Evocado Motor/efeitos dos fármacos , Córtex Motor/fisiopatologia , Plasticidade Neuronal/efeitos dos fármacos , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Fumar/patologia , Adulto , Análise de Variância , Método Duplo-Cego , Estimulação Elétrica , Eletromiografia , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Córtex Motor/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Fumar/terapia , Dispositivos para o Abandono do Uso de Tabaco , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
Our knowledge about the mechanisms of human motor cortex facilitation induced by repetitive transcranial magnetic stimulation (rTMS) is still incomplete. Here we used pharmacological conditioning with carbamazepine, dextrometorphan, lorazepam, and placebo to elucidate the type of plasticity underlying this facilitation, and to probe if mechanisms reminiscent of long-term potentiation are involved. Over the primary motor cortex of 10 healthy subjects, we applied biphasic rTMS pulses of effective posterior current direction in the brain. We used six blocks of 200 pulses at 5-Hz frequency and 90% active motor threshold intensity and controlled for corticospinal excitability changes using motor-evoked potential (MEP) amplitudes and latencies elicited by suprathreshold pulses before, in between, and after rTMS. Target muscle was the dominant abductor digiti minimi muscle; we coregistered the dominant extensor carpi radialis muscle. We found a lasting facilitation induced by this type of rTMS. The GABAergic medication lorazepam and to a lesser extent the ion channel blocker carbamazepine reduced the MEP facilitation after biphasic effective posteriorly oriented rTMS, whereas the N-methyl-d-aspartate receptor-antagonist dextrometorphan had no effect. Our main conclusion is that the mechanism of the facilitation induced by biphasic effective posterior rTMS is more likely posttetanic potentiation than long-term potentiation. Additional findings were prolonged MEP latency under carbamazepine, consistent with sodium channel blockade, and larger MEP amplitudes from extensor carpi radialis under lorazepam, suggesting GABAergic involvement in the center-surround balance of excitability.
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Potencial Evocado Motor , Potenciação de Longa Duração , Córtex Motor/fisiologia , Limiar Sensorial , Estimulação Magnética Transcraniana , Adulto , Carbamazepina/farmacologia , Feminino , Moduladores GABAérgicos/farmacologia , Humanos , Lorazepam/farmacologia , Masculino , Córtex Motor/efeitos dos fármacos , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Pirenzepina/análogos & derivados , Pirenzepina/farmacologia , Tempo de Reação , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Bloqueadores dos Canais de Sódio/farmacologiaRESUMO
Circadian rhythms exert powerful influence on various aspects of human physiology and behavior. Here, we tested changes of human cerebral cortex excitability over the course of the day with transcranial magnetic stimulation (TMS). At different times of the day, intracortical and corticospinal excitability of the primary motor cortex (M1) was evaluated in 15 healthy subjects by TMS of left M1. While motor thresholds, short-interval intracortical inhibition and facilitation and input/output curves remained unchanged, we found that a specific form of γ-aminobutyric acid (GABA)-mediated intracortical inhibition, revealed by long-interval intracortical inhibition and cortical silent periods, progressively decreased during the course of the day. Additional experiments demonstrated that morning inhibition persisted irrespective of previous sleep or sleep deprivation. Corticotropin-releasing hormone (CRH) infusions in the evening lead to morning cortisol levels but did not restore levels of morning inhibition, whereas suppression of endogenous CRH release by repeated oral dexamethasone intake over 24 h prevented morning inhibition. The findings suggest a specific modulation of GABAergic motor cortex inhibition within the circadian cycle, possibly linked to the CRH system, and may indicate a neurobiological basis for variable neuroplasticity over the course of the day.
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Ritmo Circadiano/fisiologia , Córtex Motor/fisiologia , Inibição Neural/fisiologia , Ácido gama-Aminobutírico/fisiologia , Adulto , Feminino , Humanos , Masculino , Polissonografia/métodos , Estimulação Magnética Transcraniana/métodos , Adulto JovemRESUMO
Transcranial direct current stimulation (tDCS) of the human cerebral cortex modulates cortical excitability noninvasively in a polarity-specific manner: anodal tDCS leads to lasting facilitation and cathodal tDCS to inhibition of motor cortex excitability. To further elucidate the underlying physiological mechanisms, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation of the primary motor cortex before and after a 5-min period of anodal or cathodal tDCS in eight conscious patients who had electrodes implanted in the cervical epidural space for the control of pain. The effects of anodal tDCS were evaluated in six subjects and the effects of cathodal tDCS in five subjects. Three subjects were studied with both polarities. Anodal tDCS increased the excitability of cortical circuits generating I waves in the corticospinal system, including the earliest wave (I1 wave), whereas cathodal tDCS suppressed later I waves. The motor evoked potential (MEP) amplitude changes immediately following tDCS periods were in agreement with the effects produced on intracortical circuitry. The results deliver additional evidence that tDCS changes the excitability of cortical neurons.
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Potencial Evocado Motor/fisiologia , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana , Adulto , Feminino , Lateralidade Funcional , Humanos , Masculino , Pessoa de Meia-Idade , Tratos Piramidais/fisiologia , Tempo de Reação/fisiologia , Fatores de TempoRESUMO
BACKGROUND: The purpose of this study was to determine whether transcranial direct current stimulation (tDCS) can be an effective prophylactic therapy for migraine and migraine-associated pain. METHOD: This painless and non-invasive method was applied for 6 weeks over the visual cortex (V1), delivered three times per week. Thirty patients were assigned to cathodal or to sham stimulation, and 26 patients participated in the final analyses (cathodal: n = 13, sham: n = 13). During the first 3 weeks both groups received only placebo stimulation. Measures of attack frequency and duration, intensity of pain and number of migraine-related days were recorded 2 months before, during and 2 months post-treatment. RESULTS: Patients treated by cathodal tDCS showed a significant reduction in the duration of attacks, the intensity of pain and the number of migraine-related days post-treatment as compared to the baseline period, but not in the frequency of the attacks. However, compared to the sham group, only the intensity of the pain was significantly reduced post-stimulation. No patients experienced severe adverse effects. CONCLUSION: Our results suggest that the application of cathodal stimulation over the V1 might be an effective prophylactic therapy in migraine, at least with regard to pain control.
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Transtornos de Enxaqueca/prevenção & controle , Estimulação Magnética Transcraniana/métodos , Córtex Visual/fisiologia , Adulto , Eletrodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND: Cortical excitability changes as well as imbalances in excitatory and inhibitory circuits play a distinct pathophysiological role in chronic tinnitus. Repetitive transcranial magnetic stimulation (rTMS) over the temporoparietal cortex was recently introduced to modulate tinnitus perception. In the current study, the effect of theta-burst stimulation (TBS), a novel rTMS paradigm was investigated in chronic tinnitus. Twenty patients with chronic tinnitus completed the study. Tinnitus severity and loudness were monitored using a tinnitus questionnaire (TQ) and a visual analogue scale (VAS) before each session. Patients received 600 pulses of continuous TBS (cTBS), intermittent TBS (iTBS) and intermediate TBS (imTBS) over left inferior temporal cortex with an intensity of 80% of the individual active or resting motor threshold. Changes in subjective tinnitus perception were measured with a numerical rating scale (NRS). RESULTS: TBS applied to inferior temporal cortex appeared to be safe. Although half of the patients reported a slight attenuation of tinnitus perception, group analysis resulted in no significant difference when comparing the three specific types of TBS. Converting the NRS into the VAS allowed us to compare the time-course of aftereffects. Only cTBS resulted in a significant short-lasting improvement of the symptoms. In addition there was no significant difference when comparing the responder and non-responder groups regarding their anamnestic and audiological data. The TQ score correlated significantly with the VAS, lower loudness indicating less tinnitus distress. CONCLUSION: TBS does not offer a promising outcome for patients with tinnitus in the presented study.
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Potencial Evocado Motor/fisiologia , Percepção/fisiologia , Lobo Temporal/fisiopatologia , Zumbido/patologia , Zumbido/fisiopatologia , Adulto , Estudos Cross-Over , Estimulação Elétrica/métodos , Eletroencefalografia/métodos , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Psicofísica , Método Simples-Cego , Inquéritos e Questionários , Fatores de Tempo , Estimulação Magnética Transcraniana/métodosRESUMO
Preconditioning of the human primary motor cortex (M1) with transcranial direct current stimulation (tDCS) can shape the magnitude and direction of excitability changes induced by a subsequent session of repetitive transcranial magnetic stimulation (rTMS). Here, we examined this form of metaplasticity in migraine patients with visual aura and healthy controls. In both groups, facilitatory preconditioning of left M1 with anodal tDCS increased the mean amplitudes of motor-evoked potentials (MEPs) elicited in the contralateral hand, whereas inhibitory preconditioning with cathodal tDCS produced a decrease in amplitude. Following cathodal tDCS, a short train of low-intensity 5-Hz rTMS antagonized the suppression of the mean MEP amplitude in both groups. In contrast, the homeostatic effects of 5-Hz rTMS differed between groups when rTMS was given after anodal tDCS. In controls 5-Hz rTMS induced a marked decrease in MEP amplitudes, whereas in migraineurs rTMS induced only a modest decrease in MEP amplitudes, which were still facilitated after rTMS when compared with baseline amplitudes. These findings indicate that short-term homeostatic plasticity is altered in patients with visual aura between the attacks.
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Potencial Evocado Motor/fisiologia , Enxaqueca com Aura/fisiopatologia , Córtex Motor/fisiologia , Plasticidade Neuronal/fisiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibição Neural/fisiologia , Estimulação Magnética Transcraniana , Adulto JovemRESUMO
Associative neuroplasticity, which encompasses the modification of synaptic strength by coactivation of two synaptic inputs, has been linked to learning processes. Because unlimited plasticity destabilizes neuronal networks, homeostatic rules were proposed and experimentally proven that control for the amount and direction of plasticity dependent on background network activity. Accordingly, low background activity would enhance facilitatory plasticity, whereas high background activity would inhibit it. However, the impact of background excitability on associative plasticity has not been studied so far in humans. Facilitatory associative plasticity was induced by paired associative stimulation (PAS) in the human motor cortex, whereas background activity was enhanced or diminished by transcranial direct current stimulation (tDCS). When applied before PAS, excitability-enhancing tDCS also boosted the efficacy of PAS, whereas excitability-diminishing tDCS turned it into inhibition. Thus, previous background activity does not influence associative plasticity homeostatically. When tDCS and PAS were applied simultaneously, now in accordance with homeostatic rules of neuroplasticity, reduced background activity resulted in a prolonged excitability enhancement by PAS, whereas enhanced background activity turned it into inhibition. We conclude that background network activity can influence associative plasticity homeostatically. However, only simultaneous modulation of both parameters is in accordance with homeostatic concepts. These findings might be of importance for the development of plasticity-inducing stimulation protocols supporting information processing in humans.
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Potencial Evocado Motor/fisiologia , Córtex Motor/fisiologia , Rede Nervosa/fisiologia , Plasticidade Neuronal/fisiologia , Tempo de Reação , Adulto , Feminino , Homeostase/fisiologia , Humanos , MasculinoRESUMO
It has been suggested that the left dorsolateral premotor cortex (dPMC) controls timing abilities of either hand. To further clarify its functional significance for movement timing, low-frequency repetitive transcranial magnetic stimulation (rTMS) was applied over the left and right dPMC, respectively, while subjects performed an auditorily paced finger-tapping task with each hand. rTMS over the left dPMC decreased tapping accuracy of both hands, whereas no behavioural effects occurred following right dPMC stimulation. To elucidate the time window in which left dPMC TMS disturbs synchronization abilities, pairs of TMS pulses were applied over the left dPMC and the left anterior parietal cortex serving as control condition. TMS pulses were applied randomly at 40 ms, 80 ms, 120 ms, 160 ms, 200 ms and 240 ms before pacer onset, as taps precede the pacing signal for about 20-60 ms. Again, the analysis revealed that TMS over the left dPMC disturbed synchronization abilities of either hand; however, this effect was shown at different times suggesting that the left dPMC affects the right M1 via at least one additional relay station. The present data support the hypothesis that the left dPMC is crucial for accurate timing of either hand. Additionally, they reveal a piece of evidence that the left dPMC affects the left hand not via a direct left dPMC-right M1 connection.
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Lateralidade Funcional/fisiologia , Mãos/fisiologia , Córtex Motor/fisiologia , Movimento/fisiologia , Percepção do Tempo/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Mapeamento Encefálico , Corpo Caloso/fisiologia , Potencial Evocado Motor/fisiologia , Mãos/inervação , Humanos , Masculino , Córtex Motor/anatomia & histologia , Destreza Motora/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Tempo de Reação/fisiologia , Fatores de TempoRESUMO
Neuroplasticity is the adaptive modification of network connectivity in response to environmental demands and has been identified as a major physiological correlate of learning. Since unrestricted neuroplastic modifications of network connectivity will result in a de-stabilization of the system, metaplastic modification rules have been proposed for keeping plastic connectivity changes within a useful dynamic range. In this connection, the modification threshold to achieve synaptic strengthening is thought to correlate negatively with the history of activity of the respective neurons, i.e. high previous activity enhances the threshold for synaptic strengthening and vice versa. However, the relevance of metaplasticity for actual learning processes has not been tested so far. We reduced or enhanced motor cortex excitability before performance of the serial reaction time task (SRTT), a sequential motor learning paradigm, and a reaction time task (RTT) by transcranial direct current stimulation (tDCS). If homeostatic rules apply, excitability-diminishing cathodal tDCS should improve subsequent motor learning, especially if combined with the partial NMDA receptor-agonist d-cycloserine, which selectively enhances efficacy of active receptors, while excitability-enhancing anodal tDCS should reduce it. Only the results for anodal tDCS, when combined with d-cycloserine, were in accordance with the rules of homeostatic plasticity. We conclude that homeostatic plasticity, as tested here, has a limited influence on implicit sequential motor learning.
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Potencial Evocado Motor/fisiologia , Aprendizagem/fisiologia , Córtex Motor/fisiologia , Plasticidade Neuronal/fisiologia , Tempo de Reação/fisiologia , Adulto , Análise de Variância , Antimetabólitos/farmacologia , Ciclosserina/farmacologia , Estimulação Elétrica/métodos , Potencial Evocado Motor/efeitos dos fármacos , Potencial Evocado Motor/efeitos da radiação , Feminino , Humanos , Aprendizagem/efeitos dos fármacos , Aprendizagem/efeitos da radiação , Masculino , Córtex Motor/efeitos dos fármacos , Córtex Motor/efeitos da radiação , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/efeitos da radiação , Desempenho Psicomotor/efeitos dos fármacos , Desempenho Psicomotor/fisiologia , Desempenho Psicomotor/efeitos da radiação , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/efeitos da radiação , Estimulação Magnética TranscranianaRESUMO
Motor skills, once learned, are often retained over a long period of time. However, such learning first undergoes a period of consolidation after practice. During this time, the motor memory is susceptible to being disrupted by the performance of another motor-learning task. Recently, it was shown that repetitive transcranial magnetic stimulation (rTMS) over the primary motor cortex could disrupt the retention of a newly learned ballistic task in which subjects had to oppose their index finger and thumb as rapidly as possible. Here we investigate whether the motor cortex is similarly involved during the consolidation that follows learning novel dynamics. We applied rTMS to primary motor cortex shortly after subjects had either learned to compensate for a dynamic force field applied to their index finger or learned a ballistic finger abduction task. rTMS severely degraded the retention of the learning for the ballistic task but had no effect on retention of the dynamic force-field learning. This suggests that, unlike learning of simple ballistic skills, learning of dynamics may be stored in a more distributed manner, possibly outside the primary motor cortex.
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Aprendizagem/fisiologia , Córtex Motor/fisiologia , Destreza Motora/fisiologia , Desempenho Psicomotor/fisiologia , Adulto , Feminino , Dedos/fisiologia , Humanos , Magnetismo , MasculinoRESUMO
PURPOSE: In the motor cortex (M1), transcranial direct current stimulation (tDCS) can effectively prime excitability changes that are evoked by a subsequent train of repetitive transcranial magnetic stimulation (rTMS). The authors examined whether tDCS can also prime the cortical response to rTMS in the human visual cortex. METHODS: In nine healthy subjects, the authors applied tDCS (10 minutes; +/-1 mA) to the occipital cortex. After tDCS, they applied a 20-second train of 5 Hz rTMS at 90% of phosphene threshold (PT) intensity. A similar rTMS protocol had previously demonstrated a strong priming effect of tDCS on rTMS-induced excitability changes in M1. PTs were determined with single-pulse TMS before and immediately after tDCS and twice after rTMS. RESULTS: Anodal tDCS led to a transient decrease in PT, and subsequent 5 Hz rTMS induced an earlier return of the PT back to baseline. Cathodal tDCS produced a short-lasting increase in PT, but 5 Hz rTMS did not influence the tDCS-induced increase in PT. In a control experiment on four subjects, a 20-second train of occipital 5 Hz rTMS left the PT unchanged, whereas a 60-second train produced a similar decrease in PT as anodal tDCS alone. CONCLUSIONS: Compared with previous work on the M1, tDCS and rTMS of the visual cortex only produce short-lasting changes in cortical excitability. Moreover, the priming effects of tDCS on subsequent rTMS conditioning are relatively modest. These discrepancies point to substantial differences in the modifiability of human motor and visual cortex.
Assuntos
Estimulação Elétrica , Estimulação Magnética Transcraniana , Córtex Visual/fisiologia , Adulto , Potencial Evocado Motor/fisiologia , Feminino , Humanos , Masculino , Fosfenos/fisiologia , Vias Visuais/fisiologiaRESUMO
OBJECTIVE: Low-frequency repetitive transcranial magnetic stimulation (rTMS) can reduce cortical excitability. Here we examined whether inhibitory after effects of low-frequency rTMS are influenced by stimulus intensity, the type of TMS coil and re-afferent sensory stimulation. METHODS: In fifteen healthy volunteers, we applied 900 biphasic pulses of 1Hz rTMS to the left primary motor cortex (M1) at an intensity that was 10% below or 15% above resting motor threshold. For rTMS, we used two different figure-of-eight shaped coils (Magstim or Medtronic coil) attached to the same stimulator. We recorded motor evoked potentials (MEPs) evoked with the same set-up used for rTMS (MEP-rTMS) before and twice after rTMS. Using a different TMS setup, we also applied monophasic pulses to the M1 in order to assess the effects of rTMS on corticospinal excitability, intracortical paired-pulse excitability and the duration of the cortical silent period (CSP). In a control experiment, the same measurements were performed after 15min of 1Hz repetitive electrical nerve stimulation (rENS) of the right ulnar nerve. RESULTS: Analysis of variance revealed an interaction between intensity, coil and time of measurement (p<0.035), indicating that the effect of 1Hz rTMS on MEP-rTMS amplitude depended on the intensity and the type of coil used for rTMS. Suppression of corticospinal excitability was strongest after suprathreshold 1Hz rTMS with the Medtronic coil (p<0.01 for both post-rTMS measurements relative to pre-intervention baseline). Regardless of the type of coil, suprathreshold but not subthreshold rTMS transiently prolonged the CSP and attenuated paired-pulse facilitation. Suprathreshold 1Hz rENS also induced a short-lasting inhibition of MEP-rTMS. CONCLUSIONS: Both the stimulation intensity and the type of TMS coil have an impact on the after effects of 1Hz rTMS. Re-afferent feedback activation may at least in part account for the stronger suppression of corticospinal excitability by suprathreshold 1Hz rTMS. SIGNIFICANCE: These data should be considered when rTMS is used as a therapeutic means.