RESUMO
Neuroimaging studies of the psychedelic state offer a unique window onto the neural basis of conscious perception and selfhood. Despite well understood pharmacological mechanisms of action, the large-scale changes in neural dynamics induced by psychedelic compounds remain poorly understood. Using source-localised, steady-state MEG recordings, we describe changes in functional connectivity following the controlled administration of LSD, psilocybin and low-dose ketamine, as well as, for comparison, the (non-psychedelic) anticonvulsant drug tiagabine. We compare both undirected and directed measures of functional connectivity between placebo and drug conditions. We observe a general decrease in directed functional connectivity for all three psychedelics, as measured by Granger causality, throughout the brain. These data support the view that the psychedelic state involves a breakdown in patterns of functional organisation or information flow in the brain. In the case of LSD, the decrease in directed functional connectivity is coupled with an increase in undirected functional connectivity, which we measure using correlation and coherence. This surprising opposite movement of directed and undirected measures is of more general interest for functional connectivity analyses, which we interpret using analytical modelling. Overall, our results uncover the neural dynamics of information flow in the psychedelic state, and highlight the importance of comparing multiple measures of functional connectivity when analysing time-resolved neuroimaging data.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Conectoma , Alucinógenos/farmacologia , Ketamina/farmacologia , Dietilamida do Ácido Lisérgico/farmacologia , Magnetoencefalografia/efeitos dos fármacos , Rede Nervosa/efeitos dos fármacos , Psilocibina/farmacologia , Adulto , Anticonvulsivantes/farmacologia , Córtex Cerebral/fisiologia , Feminino , Alucinógenos/administração & dosagem , Humanos , Ketamina/administração & dosagem , Dietilamida do Ácido Lisérgico/administração & dosagem , Masculino , Rede Nervosa/fisiologia , Psilocibina/administração & dosagem , Tiagabina/farmacologia , Adulto JovemRESUMO
BACKGROUND: Investigations of the electrophysiology of gaseous anesthetics xenon and nitrous oxide are limited revealing inconsistent frequency-dependent alterations in spectral power and functional connectivity. Here, the authors describe the effects of sedative, equivalent, stepwise levels of xenon and nitrous oxide administration on oscillatory source power using a crossover design to investigate shared and disparate mechanisms of gaseous xenon and nitrous oxide anesthesia. METHODS: Twenty-one healthy males underwent simultaneous magnetoencephalography and electroencephalography recordings. In separate sessions, sedative, equivalent subanesthetic doses of gaseous anesthetic agents nitrous oxide and xenon (0.25, 0.50, and 0.75 equivalent minimum alveolar concentration-awake [MACawake]) and 1.30 MACawake xenon (for loss of responsiveness) were administered. Source power in various frequency bands were computed and statistically assessed relative to a conscious/pre-gas baseline. RESULTS: Observed changes in spectral-band power (P < 0.005) were found to depend not only on the gas delivered, but also on the recording modality. While xenon was found to increase low-frequency band power only at loss of responsiveness in both source-reconstructed magnetoencephalographic (delta, 208.3%, 95% CI [135.7, 281.0%]; theta, 107.4%, 95% CI [63.5, 151.4%]) and electroencephalographic recordings (delta, 260.3%, 95% CI [225.7, 294.9%]; theta, 116.3%, 95% CI [72.6, 160.0%]), nitrous oxide only produced significant magnetoencephalographic high-frequency band increases (low gamma, 46.3%, 95% CI [34.6, 57.9%]; high gamma, 45.7%, 95% CI [34.5, 56.8%]). Nitrous oxide-not xenon-produced consistent topologic (frontal) magnetoencephalographic reductions in alpha power at 0.75 MACawake doses (44.4%; 95% CI [-50.1, -38.6%]), whereas electroencephalographically nitrous oxide produced maximal reductions in alpha power at submaximal levels (0.50 MACawake, -44.0%; 95% CI [-48.1,-40.0%]). CONCLUSIONS: Electromagnetic source-level imaging revealed widespread power changes in xenon and nitrous oxide anesthesia, but failed to reveal clear universal features of action for these two gaseous anesthetics. Magnetoencephalographic and electroencephalographic power changes showed notable differences which will need to be taken into account to ensure the accurate monitoring of brain state during anaesthesia.
Assuntos
Anestésicos Inalatórios/administração & dosagem , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/diagnóstico por imagem , Estado de Consciência/efeitos dos fármacos , Óxido Nitroso/administração & dosagem , Xenônio/administração & dosagem , Adulto , Córtex Cerebral/fisiologia , Estado de Consciência/fisiologia , Estudos Cross-Over , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/métodos , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética/métodos , Magnetoencefalografia/efeitos dos fármacos , Magnetoencefalografia/métodos , Masculino , Método Simples-Cego , Adulto JovemRESUMO
Neurophysiological recordings are dominated by arhythmical activity whose spectra can be characterised by power-law functions, and on this basis are often referred to as reflecting scale-free brain dynamics (1/fß). Relatively little is known regarding the neural generators and temporal dynamics of this arhythmical behaviour compared to rhythmical behaviour. Here we used Irregularly Resampled AutoSpectral Analysis (IRASA) to quantify ß, in both the high (5-100â¯Hz, ßhf) and low frequency bands (0.1-2.5â¯Hz, ßlf) in MEG/EEG/ECoG recordings and to separate arhythmical from rhythmical modes of activity, such as, alpha rhythms. In MEG/EEG/ECoG data, we demonstrate that oscillatory alpha power dynamically correlates over time with ßhf and similarly, participants with higher rhythmical alpha power have higher ßhf. In a series of pharmaco-MEG investigations using the GABA reuptake inhibitor tiagabine, the glutamatergic AMPA receptor antagonist perampanel, the NMDA receptor antagonist ketamine and the mixed partial serotonergic agonist LSD, a variety of effects on both ßhf and ßlf were observed. Additionally, strong modulations of ßhf were seen in monkey ECoG data during general anaesthesia using propofol and ketamine. We develop and test a unifying model which can explain, the 1/f nature of electrophysiological spectra, their dynamic interaction with oscillatory rhythms as well as the sensitivity of 1/f activity to drug interventions by considering electrophysiological spectra as being generated by a collection of stochastically perturbed damped oscillators having a distribution of relaxation rates.
Assuntos
Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Modelos Neurológicos , Adulto , Animais , Mapeamento Encefálico/métodos , Eletrocorticografia/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Feminino , Inibidores da Captação de GABA/farmacologia , Haplorrinos , Humanos , Hipnóticos e Sedativos/farmacologia , Ketamina/farmacologia , Dietilamida do Ácido Lisérgico/farmacologia , Magnetoencefalografia/efeitos dos fármacos , Masculino , Nitrilas , Propofol/farmacologia , Piridonas/farmacologia , Receptores de AMPA/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Antagonistas da Serotonina/farmacologia , Tiagabina/farmacologia , Adulto JovemRESUMO
BACKGROUND: In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation. METHODS: Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale. RESULTS: Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150 ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy. CONCLUSIONS: The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success.
Assuntos
Antidepressivos/uso terapêutico , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/metabolismo , Emoções/fisiologia , Magnetoencefalografia/métodos , Adulto , Antidepressivos/farmacologia , Estudos de Casos e Controles , Transtorno Depressivo Maior/diagnóstico , Emoções/efeitos dos fármacos , Feminino , Seguimentos , Humanos , Magnetoencefalografia/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Pain is a complex subjective phenomenon that so far cannot be objectively quantified by any standardized procedure. This fact renders it also difficult to measure the efficacy of analgesic drugs. In recent years the application of functional magnetic resonance imaging (fMRI) has significantly increased our current knowledge about the brain physiological correlates of pain in humans. The technique is non-invasive and detects the increased blood flow into neuronally active brain regions based on the so-called BOLD (blood oxygenation level dependent) effect of T2-weighted MRI. This paper gives an overview of the application of pharmacological fMRI (phfMRI) as an approach to evaluate the efficacy of analgesics. In contrast to EEG- and MEG-based methods phfMRI allows more flexibility in the design of experimental paradigms and stimulus protocols to account for the diversity of clinical pain types (inflammatory pain, tactile allodynia etc.) or their dependence upon psychological circumstances (anxiety, depression, stress) in which pain occurs. However, in order to specifically refer results from phfMRI to the neuronal processes underlying pain, future research needs to increase the understanding of the mechanisms underlying the neurovascular coupling reaction represented by the BOLD technique. The same applies for the influence of cerebrovascular diseases on the BOLD response.
Assuntos
Analgésicos/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Oxigênio/sangue , Dor/tratamento farmacológico , Dor/fisiopatologia , Encéfalo/irrigação sanguínea , Mapeamento Encefálico , Eletroencefalografia/efeitos dos fármacos , Humanos , Magnetoencefalografia/efeitos dos fármacos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Resultado do TratamentoRESUMO
BACKGROUND: Magnetoencephalography (MEG) is increasingly used in the presurgical evaluation of pediatric seizure patients. Many pediatric patients require sedation or anesthesia to tolerate these exams. However, the available literature on anesthetic management in this population is very limited. METHODS: We retrospectively reviewed the records of all patients who underwent MEG scanning at our institution with regard to the interaction of anesthetic management and quality of scan data. RESULTS: High-dose propofol infusions (> or =200 microg.kg(-1).min(-1)) were associated with high frequency artifacts that interfered with the identification of epileptiform discharges. Lower-dose propofol infusions (< or =100 microg.kg(-1).min(-1)) did not produce artifacts but required co-administration of fentanyl to prevent patient motion. Dexmedetomidine infusions were not associated with signal artifacts and prevented patient motion very well in our initial patients and became our standard technique. CONCLUSION: In our experience, dexmedetomidine infusions are preferable to propofol-based techniques for pediatric MEG scans due to the absence of adverse effect on interictal activity.
Assuntos
Anestesia/métodos , Dexmedetomidina/farmacologia , Magnetoencefalografia/efeitos dos fármacos , Cuidados Pré-Operatórios/métodos , Propofol/farmacologia , Adolescente , Analgésicos não Narcóticos/farmacologia , Anestésicos Intravenosos/farmacologia , Artefatos , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Epilepsia/diagnóstico , Epilepsia/cirurgia , Feminino , Fentanila/administração & dosagem , Humanos , Magnetoencefalografia/métodos , Masculino , Estudos RetrospectivosRESUMO
Preclinical and clinical evidence has demonstrated that ketamine has rapid antidepressant effects. Studies using pre-treatment with an AMPA inhibitor suggest that enhancing AMPA throughput is crucial to ketamine's effects, including increases in both basal and evoked gamma power. This study sought to replicate previous findings of increased gamma response to a somatosensory stimulus at 230 min and Day 1 in ketamine responders versus non-responders in 31 depressed subjects and 25 healthy controls. A significant difference in peak gamma power was seen in the depressed ketamine responders versus non-responders. These results implicate AMPA throughput in ketamine's mechanism of antidepressant action.
Assuntos
Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Ketamina/uso terapêutico , Magnetoencefalografia/efeitos dos fármacos , Potenciais Sinápticos/efeitos dos fármacos , Adulto , Anestésicos Dissociativos/farmacologia , Anestésicos Dissociativos/uso terapêutico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Estudos Cross-Over , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Resistente a Tratamento/diagnóstico por imagem , Método Duplo-Cego , Feminino , Humanos , Ketamina/farmacologia , Magnetoencefalografia/métodos , Masculino , Potenciais Sinápticos/fisiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: The psychomotor stimulant methylphenidate (MPH) has been shown to improve attentional processes, reflected in behavioural measures such as vigilance, reaction time and visual attention tasks. The neural mechanisms of MPH action on sensory information processing, however, remain poorly understood. To the authors' knowledge, this present study is the first to investigate whether a single dose of MPH affects neural substrates of passive attention in healthy adults studied with simultaneous whole-head magnetoencephalography (MEG) and electroencephalography (EEG). METHODS: Monaural left-ear auditory stimuli were presented in an oddball paradigm with infrequent deviant tones differing in frequency and duration. Neuronal activity was recorded with simultaneous whole-head MEG and EEG in 13 healthy subjects (five females; aged 27 +/- 5 years) after oral administration of 40 mg MPH or placebo in a randomised, double-blind, cross-over design. We analysed both electric and magnetic N100, P200 and mismatch negativity (MMN) components. RESULTS: MPH increased arousal levels in visual analogue scales. MPH had no effect on the dipole strength of MMN or MMNm in either frequency or duration deviations. MPH did, however, reduce P200 amplitudes in EEG. CONCLUSIONS: The lack of effect of MPH on either MMN or MMNm suggests no association between catecholaminergic activities and MMN generation. However, our findings imply that MPH may change the neural bases of auditory information processing such as the early stimulus evaluation reflected in the P200 component. Dopamine and noradrenaline neurotransmitter systems could be responsible for the modulation of these processes. The exclusive effect of MPH on the P200 component could have a clinical application.
Assuntos
Atenção/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Eletroencefalografia/efeitos dos fármacos , Magnetoencefalografia/efeitos dos fármacos , Metilfenidato/farmacologia , Discriminação da Altura Tonal/efeitos dos fármacos , Percepção do Tempo/efeitos dos fármacos , Estimulação Acústica , Adulto , Nível de Alerta/efeitos dos fármacos , Mapeamento Encefálico , Córtex Cerebral/efeitos dos fármacos , Variação Contingente Negativa/efeitos dos fármacos , Dominância Cerebral/fisiologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Feminino , Humanos , Masculino , Tempo de Reação/efeitos dos fármacosRESUMO
OBJECTIVE: With MEG and EEG the effect of perinatal dioxin load of 38 healthy 7- to 12-year-old children was studied to assess possible disturbances of visual development. METHODS: Latencies and amplitudes of the motion (N2 with subcomponents) and oddball responses (N200 and P3b) were analysed after age correction. RESULTS: With increasing load, latencies increased and the amplitudes of the oddball components tended to be reduced. The latency increase between the high- and low-loaded children was about 13 ms (P<0.004) and the oddball response showed an amplitude decrease of 12% (P=0.009). CONCLUSIONS: It may be concluded that, during the end-80s/early-90s, exposure to background levels in industrialized regions seems to have resulted in small underdevelopment or damage to visual motion processing and visual cognition. SIGNIFICANCE: Since dioxin pollution by incinerators still exists in many regions in developing countries and also still, although at a smaller scale, in the industrialized world, perinatal loads of similar magnitude and possibly more as measured in this study may occur and as a consequence might affect the developing brain.
Assuntos
Deficiências do Desenvolvimento/induzido quimicamente , Deficiências do Desenvolvimento/prevenção & controle , Dioxinas/toxicidade , Eletroencefalografia/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Magnetoencefalografia/efeitos dos fármacos , Percepção de Movimento/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/psicologia , Desempenho Psicomotor/efeitos dos fármacos , Percepção Visual/efeitos dos fármacos , Tecido Adiposo/química , Envelhecimento/psicologia , Criança , Depressão Química , Dioxinas/análise , Relação Dose-Resposta a Droga , Poluentes Ambientais/análise , Potenciais Evocados Visuais/efeitos dos fármacos , Feminino , Humanos , Recém-Nascido , Modelos Lineares , Masculino , Países Baixos , Estimulação Luminosa , Gravidez , Valores de Referência , Visão Binocular/efeitos dos fármacosRESUMO
Disturbances in integrative function have been consistentLy described in psychotic disorder; for instance, prepulse inhibition of the startle reflex (startle-PPI) which is a marker of sensory gating, is deficient in persons with schizophrenia. The N-methyl-D-aspartate antagonist ketamine produces in control subjects a spectrum of neurobehavioural symptoms like encountered in schizophrenia, and disrupts startle-PPI in animals. In the present study, we investigated in 12 healthy subjects whether ketamine would reduce sensory-gating in auditory responses at doses which produce psychotic symptoms. In a double-blind, crossover design loading doses of 0.024, 0.081 and 0.27 mg/kg or saline were employed, followed by maintenance infusion for 120 min. A passive paradigm has been developed which consisted in tone bursts, preceded or not by a (near-threshold) click at intervals of 100 ms or 500 ms. Brain electromagnetic activity imaging of the responses to sound stimuli has been carried out by way of a 148-channel magnetoencephalography-system. Actual evoked response amplitudes and underlying equivalent current dipole strengths have been compared to multi-electrode evoked potentials from the scalp. A click stimulus is capable to inhibit test responses under placebo at the 100 ms interval. During maintenance infusion of ketamine at steady-state (for >30 min) after 0.27 mg/kg, no such amplitude changes were observed anymore (p <0.05) and under these circumstances significant increases in Brief Psychiatric Rating scale and Scale for the Assessment of Negative Symptoms scores were evidenced (p < 0.001). Intermediate effects have been observed when the dose was lowered to 0.081 mg/kg. The present results have shown that ketamine may induce a psychotic-like clinical state associated with gating deficits in healthy subjects.
Assuntos
Percepção Auditiva/efeitos dos fármacos , Eletroencefalografia/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Magnetoencefalografia/efeitos dos fármacos , Psicoses Induzidas por Substâncias/psicologia , Estimulação Acústica , Adulto , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A magnetoencephalography (MEG) study requires the patient to lie still for a prolonged period of time. In children and uncooperative adults with epilepsy, general anesthesia or sedation may be required to insure a good quality study. As general anesthetics have anticonvulsant and proconvulsant properties, we investigated whether the use of anesthesia reduced the successful detection of interictal epilepsy activity. METHODS: MEG testing was performed on 41 epilepsy patients (10 women, 31 men; 1-48 yr) while anesthetized. To determine the impact of anesthesia on the identification of epileptiform activity, the anesthesia group of patients was compared with all other patients with epilepsy who were recorded in our laboratory without anesthesia, as well as with a subgroup of children with epilepsy who were able to be recorded without the need for anesthesia. RESULTS: Propofol was used in 38 patients, etomidate in two, and one received sevoflurane. Twenty-nine (71%) were found to have interictal epileptiform activity in their MEG results. The percentage of MEG studies with a positive yield for interictal epileptiform activity is comparable with the percentage (63%) found in the patients with epilepsy undergoing MEG without anesthesia. In the 38 children younger than 18 yr, 28 (74%) had interictal epileptiform activity compared with 80% done without anesthesia. CONCLUSION: We conclude that levels of anesthesia needed to provide unconsciousness and immobility during MEG studies do not significantly alter the likelihood of recording interictal epileptiform spike activity with MEG.
Assuntos
Anestésicos Gerais/farmacologia , Epilepsia/fisiopatologia , Magnetoencefalografia/efeitos dos fármacos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
INTRODUCTION: Chronic alcohol abuse is associated with neurophysiological changes in brain activity; however, these changes are not well localized in humans. Non-human primate models of alcohol abuse enable control over many potential confounding variables associated with human studies. The present study utilized high-resolution magnetoencephalography (MEG) to quantify the effects of chronic EtOH self-administration on resting state (RS) brain function in vervet monkeys. METHODS: Adolescent male vervet monkeys were trained to self-administer ethanol (n=7) or an isocaloric malto-dextrin solution (n=3). Following training, animals received 12 months of free access to ethanol. Animals then underwent RS magnetoencephalography (MEG) and subsequent power spectral analysis of brain activity at 32 bilateral regions of interest associated with the chronic effects of alcohol use. RESULTS: demonstrate localized changes in brain activity in chronic heavy drinkers, including reduced power in the anterior cingulate cortex, hippocampus, and amygdala as well as increased power in the right medial orbital and parietal areas. DISCUSSION: The current study is the first demonstration of whole-head MEG acquisition in vervet monkeys. Changes in brain activity were consistent with human electroencephalographic studies; however, MEG was able to extend these findings by localizing the observed changes in power to specific brain regions. These regions are consistent with those previously found to exhibit volume loss following chronic heavy alcohol use. The ability to use MEG to evaluate changes in brain activity following chronic ethanol exposure provides a potentially powerful tool to better understand both the acute and chronic effects of alcohol on brain function.
Assuntos
Consumo de Bebidas Alcoólicas/fisiopatologia , Consumo de Bebidas Alcoólicas/tendências , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Etanol/administração & dosagem , Intoxicação Alcoólica/fisiopatologia , Animais , Chlorocebus aethiops , Eletroencefalografia/efeitos dos fármacos , Eletroencefalografia/tendências , Magnetoencefalografia/efeitos dos fármacos , Magnetoencefalografia/tendências , Masculino , Primatas , AutoadministraçãoRESUMO
The ionotropic N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors of the glutamatergic neurotransmitter system are of fundamental importance to healthy brain function. Neuroimaging studies in humans have previously been conducted using various drugs that interact with N-methyl-D-aspartate glutamate receptors, but no such studies have investigated AMPA receptor signalling. The recent approval of perampanel (Fycompa) for use in humans provides a means to specifically study the role of AMPA receptors in the pharmacological basis of neuroimaging signals. Twenty male subjects participated in this placebo-controlled crossover study that consisted of two study days separated by a minimum two-week washout period. On one occasion participants ingested a 6 mg dose of perampanel, and on the other a placebo. Ten minutes of wakeful rest was recorded before and after each dose using magnetoencephalography. Subjective ratings of intoxication were significantly higher following drug than placebo. Cluster-based randomisation testing of sensor-level magnetoencephalography data showed significant drug-induced increases in low frequency power (1-4 Hz, 4-8 Hz, 8-13 Hz, 13-30 Hz), along with a significant decrease in the high gamma range (50-90 Hz). We also observed selective increases in functional connectivity in the alpha and beta bands. The findings are consistent with preclinical work and are similar to the spectral profile of other anti-epileptic drugs.
Assuntos
Ondas Encefálicas/efeitos dos fármacos , Magnetoencefalografia/efeitos dos fármacos , Piridonas/farmacologia , Receptores de AMPA/antagonistas & inibidores , Adolescente , Adulto , Anticonvulsivantes/farmacologia , Estudos Cross-Over , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas , Adulto JovemRESUMO
OBJECTIVES: Deep brain stimulation (DBS) and dopaminergic medication effectively alleviate the motor symptoms in Parkinson's disease (PD) patients, but their effects on the sensory symptoms of PD are still not well understood. To explore early somatosensory processing in PD, we recorded magnetoencephalography (MEG) from thirteen DBS-treated PD patients and ten healthy controls during median nerve stimulation. METHODS: PD patients were measured during DBS-treated, untreated and dopaminergic-medicated states. We focused on early cortical somatosensory processing as indexed by N20m, induced gamma augmentation (31-45Hz and 55-100Hz) and induced beta suppression (13-30Hz). PD patients' motor symptoms were assessed by UPDRS-III. RESULTS: Using Bayesian statistics, we found positive evidence for differentiated effects of treatments on the induced gamma augmentation (31-45Hz) with highest gamma in the dopaminergic-medicated state and lowest in the DBS-treated and untreated states. In contrast, UPDRS-III scores showed beneficial effects of both DBS and dopaminergic medication on the patients' motor symptoms. Furthermore, treatments did not affect the amplitude of N20m. CONCLUSIONS: Our results suggest differentiated effects of DBS and dopaminergic medication on cortical somatosensory processing in PD patients despite consistent ameliorating effects of both treatments on PD motor symptoms. SIGNIFICANCE: The differentiated effect suggests differences in the effect mechanisms of the two treatments.
Assuntos
Antiparkinsonianos/uso terapêutico , Estimulação Encefálica Profunda/métodos , Potenciais Somatossensoriais Evocados/fisiologia , Magnetoencefalografia/métodos , Doença de Parkinson/fisiopatologia , Córtex Somatossensorial/fisiopatologia , Antiparkinsonianos/farmacologia , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Feminino , Humanos , Magnetoencefalografia/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/terapia , Córtex Somatossensorial/efeitos dos fármacosRESUMO
Paroxysmal kinesigenic dyskinesia (PKD) is a rare group of hyperkinetic movement disorders characterized by brief attacks of choreoathetosis or dystonia. To clarify the alterations of the functional connectivity within the somatosensory network in PKD patients, magnetoencephalographic (MEG) responses to paired median-nerve electrical stimulation were recorded in 10 PKD patients treated by carbamazepine or oxcarbamazepine and 22 age-matched controls. In patients, MEG recordings were obtained during drug-on and -off periods. Source-based functional connectivity analysis was performed between contralateral primary (cSI) and secondary (cSII), and ipsilateral secondary (iSII) somatosensory areas. During drug-off periods, patients with PKD demonstrated decreased cSI-iSII and increased cSII-iSII somatosensory connectivity at theta band. Drug-on periods lowered the functional connectivity in cSI-cSII at alpha and beta bands and in cSII-iSII at theta band compared with the drug-off periods. We suggest that altered theta functional connectivity in cSI-iSII and cSII-iSII could be the neurophysiological signatures in PKD.
Assuntos
Ondas Encefálicas/efeitos dos fármacos , Sincronização Cortical/efeitos dos fármacos , Distonia/tratamento farmacológico , Distonia/fisiopatologia , Magnetoencefalografia/métodos , Córtex Somatossensorial/efeitos dos fármacos , Córtex Somatossensorial/fisiopatologia , Adolescente , Anticonvulsivantes/uso terapêutico , Mapeamento Encefálico/métodos , Criança , Feminino , Humanos , Magnetoencefalografia/efeitos dos fármacos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To investigate whether effects of the glutamatergic N-methyl-d-aspartate (NMDA) receptor antagonist ketamine on the mismatch negativity (MMN) vary between duration and frequency deviants, as suggested by clinical studies on schizophrenia patients. METHODS: Our meta-analysis included previous studies that used ketamine in order to induce psychotic experiences in healthy participants and that recorded the MMN either by electroencephalography or magnetoencephalography. RESULTS: The analysis revealed systematic MMN amplitude decreases and, with a lower effect size, latency increases after ketamine administration. However, the observed amplitude and latency effects did not vary between duration and frequency deviants. CONCLUSION: Across studies, there is no evidence that ketamine effects on the MMN are larger for duration than frequency deviants. SIGNIFICANCE: Our findings tentatively suggest that, in addition to an NMDA receptor hypofunction, other factors might contribute to the sometimes observed pattern of impaired MMN responses to duration deviants, but unimpaired MMN responses to frequency deviants in schizophrenia.
Assuntos
Eletroencefalografia/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Ketamina/farmacologia , Magnetoencefalografia/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Percepção Auditiva/efeitos dos fármacos , Percepção Auditiva/fisiologia , Eletroencefalografia/métodos , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Humanos , Magnetoencefalografia/métodosRESUMO
RATIONALE: Alcohol has been shown to impair involuntary attention studied by event-related potentials using mismatch negativity (MMN) and P3a. OBJECTIVES: However, no studies have investigated whether alcohol affects the magnetic counterparts of N1 (N1m), MMN (MMNm) and P3a (P3am). METHODS: Auditory evoked potentials and magnetic fields elicited by infrequent deviant tones differing in frequency (5% and 20% change) and novel sounds were recorded with whole-head magnetoencephalography (MEG) and electroencephalography (EEG). Stimuli were presented separately to the left and right ear. Eleven right-handed subjects were studied in a double-blind, placebo-controlled (0.8 g/kg ethanol or juice), cross-over design. N1m, MMNm, and P3am were calculated from the channel pair at the temporal cortex showing the strongest responses in the hemisphere contralateral to the stimulation. N1, MMN and P3a were analyzed from 12 electrodes at the midline frontocentral area. RESULTS: Alcohol reduced bilaterally N1, N1m, MMN and MMNm amplitudes. P3a amplitudes, but not P3am amplitudes were also significantly decreased. No effects of alcohol on the latencies of N1, MMN and P3a or their magnetic counterparts were observed. CONCLUSIONS: Alcohol impairs the processing of tones, frequency change and novel sounds at different phases of auditory processing similarly in both hemispheres. MEG provides us with additional information unobtainable with EEG about the effects of alcohol on the neural correlates of cognition.
Assuntos
Percepção Auditiva/efeitos dos fármacos , Depressores do Sistema Nervoso Central/farmacologia , Eletroencefalografia/efeitos dos fármacos , Etanol/farmacologia , Magnetoencefalografia/efeitos dos fármacos , Percepção da Altura Sonora/efeitos dos fármacos , Estimulação Acústica , Adulto , Algoritmos , Atenção/efeitos dos fármacos , Estudos Cross-Over , Interpretação Estatística de Dados , Método Duplo-Cego , Potenciais Evocados Auditivos/efeitos dos fármacos , Feminino , Humanos , MasculinoRESUMO
OBJECTIVE: This study aimed to investigate previously observed side effects, i.e. increased epileptic activity during clonidine medication. The safety and effectiveness of clonidine as spike inducing agent compared to sleep deprivation were tested. METHODS: Patients suffering from drug-resistant localization related epilepsy took part in 3 magnetoencephalography (MEG) sessions. One session was recorded without any activating measures. The other two sessions were either performed after sleep deprivation or after medication with clonidine. Target parameter was the number of spikes or sharp-waves during a 30 min recording period. RESULTS: About 67% of the patients showed increased spike activity after clonidine, whereas sleep deprivation increased the number of spikes in 33%, and 29% of the patients did not show any activation at all. Clonidine was most effective in temporal lobe epilepsy, when the focus was located in the right hemisphere, and when clonidine serum concentrations were ranging between 0.6 and 1.0 ng/ml. CONCLUSIONS: This study showed for the first time that clonidine can be considered an effective spike or sharp-wave inducing drug that is superior to the potency of sleep deprivation. SIGNIFICANCE: The administration of clonidine increases the probability of recording ictal and interictal epileptic activity during limited acquisition time.
Assuntos
Potenciais de Ação/efeitos dos fármacos , Clonidina/farmacologia , Magnetoencefalografia/efeitos dos fármacos , Privação do Sono/fisiopatologia , Potenciais de Ação/fisiologia , Adolescente , Adulto , Clonidina/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Feminino , Humanos , Magnetoencefalografia/métodos , Masculino , Pessoa de Meia-Idade , Estatísticas não ParamétricasRESUMO
Electroencephalography (EEG) and magnetoencephalography (MEG) can detect different aspects of alcohol effects on auditory processing measured with event-related potentials and magnetic fields. The present study aimed to detect alcohol-induced changes in spontaneous neuronal oscillations with combined EEG and MEG techniques. The effects of alcohol on spontaneous neuronal rhythms were studied in 12 healthy subjects after 0.8 g/kg alcohol or juice in a double-blind, placebo-controlled, cross-over design using simultaneous high-resolution MEG and EEG in eyes-open and eyes-closed conditions. The data were analyzed with a power spectral density analysis. MEG recording showed that alcohol significantly increased the relative power of alpha rhythm (8-10 Hz) and reduced the relative power of beta activity (17-25 Hz) in both left and right hemispheres, but only in the eyes-closed condition. These effects did not depend on gender. No analogous statistically significant changes were observed in EEG rhythms. However, the power of alpha and beta rhythms was positively correlated in MEG and EEG recordings, indicating that MEG and EEG reflect similar processes. A distinct sensitivity of MEG and EEG to the sources of cortical oscillations, a better signal-to-noise ratio of MEG, as well as strong spatial blurring of potentials in EEG are most likely the reasons for the observed differences in the effects of alcohol on spontaneous oscillations as detected with two methods.
Assuntos
Depressores do Sistema Nervoso Central/farmacologia , Eletroencefalografia/efeitos dos fármacos , Etanol/farmacologia , Magnetoencefalografia/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Adulto , Depressores do Sistema Nervoso Central/sangue , Estudos Cross-Over , Método Duplo-Cego , Etanol/sangue , Feminino , Lateralidade Funcional/fisiologia , Humanos , Masculino , Caracteres SexuaisRESUMO
BACKGROUND: The present study was dedicated to investigate the influence of Methylphenidate (MPH) on cortical processing of children who were diagnosed with different subtypes of Attention Deficit Hyperactivity Disorder (ADHD). As all of the previous studies investigating power differences in different frequency bands have been using EEG, mostly with a relatively small number of electrodes our aim was to obtain new aspects using high density magnetoencephalography (MEG). METHODS: 35 children (6 female, 29 male) participated in this study. Mean age was 11.7 years (+/- 1.92 years). 17 children were diagnosed of having an Attention-Deficit/Hyperactivity Disorder of the combined type (ADHDcom, DSM IV code 314.01); the other 18 were diagnosed for ADHD of the predominantly inattentive type (ADHDin, DSM IV code 314.0). We measured the MEG during a 5 minute resting period with a 148-channel magnetometer system (MAGNES 2500 WH, 4D Neuroimaging, San Diego, USA). Power values were averaged for 5 bands: Delta (D, 1.5-3.5 Hz), Theta (T, 3.5-7.5 Hz), Alpha (A, 7.5-12.5 Hz), Beta (B, 12.5-25 Hz) and Global (GL, 1.5-25 Hz).). Additionally, attention was measured behaviourally using the D2 test of attention with and without medication. RESULTS: The global power of the frequency band from 1.5 to 25 Hz increased with MPH. Relative Theta was found to be higher in the left hemisphere after administration of MPH than before. A positive correlation was found between D2 test improvement and MPH-induced power changes in the Theta band over the left frontal region. A linear regression was computed and confirmed that the larger the improvement in D2 test performance, the larger the increase in Theta after MPH application. CONCLUSION: Main effects induced by medication were found in frontal regions. Theta band activity increased over the left hemisphere after MPH application. This finding contradicts EEG results of several groups who found lower levels of Theta power after MPH application. As relative Theta correlates with D2 test improvement we conclude that MEG provide complementary and therefore important new insights to ADHD.