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1.
Int J Psychophysiol ; 134: 30-43, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30253197

RESUMO

In this study we present the test-retest reliability of pre-intervention EEG/ERP (electroencephalogram/event-related potentials) data across four recording intervals separated by a washout period (18-22 days). POz-recording-reference EEG/ERP (28 sites, average reference) were recorded from thirty-two healthy male participants. Participants were randomly allocated into different intervention sequences, each with four intervention regimens: 10 mg vortioxetine, 20 mg vortioxetine, 15 mg escitalopram and Placebo. We report classical EEG spectra: δ (1-4 Hz), θ (4-8 Hz), α (8-12 Hz), ß (12-30 Hz), γ1 (30-45 Hz) and γ2 (45-80 Hz) of resting state and vigilance-controlled, and of auditory steady state response, as well as ERP components N100, P200 and P300 in auditory oddball task and error related negativity (ERN) and error positivity (Pe) in hybrid flanker task. Reliability was quantified using intra-class correlation coefficient (ICC). We found that θ, α and ß of continuous EEG were highly reliable (ICCs ≥ 0.84). Evoked power of other tasks demonstrated larger variability and less reliability compared to the absolute power of continuous EEG. Furthermore, reliabilities of ERP measures were lower compared to those of the EEG spectra. We saw fair to excellent reliability of the amplitude of the components such as Pe (0.60-0.82) and P300 (0.55-0.80). Moreover, blood tests confirmed that there was no measurable drug carry-over from the previous intervention. The results support that EEG/ERP is reliable across four recording intervals, thus it can be used to assess the effect of different doses and types of drugs with CNS effects.


Assuntos
Citalopram/farmacologia , Eletroencefalografia/normas , Potenciais Evocados/fisiologia , Inibidores de Captação de Serotonina/farmacologia , Vortioxetina/farmacologia , Adulto , Ondas Encefálicas/efeitos dos fármacos , Ondas Encefálicas/fisiologia , Citalopram/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Eletroencefalografia/efeitos dos fármacos , Potencial Evocado P300/efeitos dos fármacos , Potencial Evocado P300/fisiologia , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Humanos , Masculino , Reprodutibilidade dos Testes , Inibidores de Captação de Serotonina/administração & dosagem , Fatores de Tempo , Vortioxetina/administração & dosagem , Adulto Jovem
2.
J Neurosci Methods ; 235: 262-76, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25088694

RESUMO

BACKGROUND: Manual scoring of sleep relies on identifying certain characteristics in polysomnograph (PSG) signals. However, these characteristics are disrupted in patients with neurodegenerative diseases. NEW METHOD: This study evaluates sleep using a topic modeling and unsupervised learning approach to identify sleep topics directly from electroencephalography (EEG) and electrooculography (EOG). PSG data from control subjects were used to develop an EOG and an EEG topic model. The models were applied to PSG data from 23 control subjects, 25 patients with periodic leg movements (PLMs), 31 patients with idiopathic REM sleep behavior disorder (iRBD) and 36 patients with Parkinson's disease (PD). The data were divided into training and validation datasets and features reflecting EEG and EOG characteristics based on topics were computed. The most discriminative feature subset for separating iRBD/PD and PLM/controls was estimated using a Lasso-regularized regression model. RESULTS: The features with highest discriminability were the number and stability of EEG topics linked to REM and N3, respectively. Validation of the model indicated a sensitivity of 91.4% and a specificity of 68.8% when classifying iRBD/PD patients. COMPARISON WITH EXISTING METHOD: The topics showed visual accordance with the manually scored sleep stages, and the features revealed sleep characteristics containing information indicative of neurodegeneration. CONCLUSIONS: This study suggests that the amount of N3 and the ability to maintain NREM and REM sleep have potential as early PD biomarkers. Data-driven analysis of sleep may contribute to the evaluation of neurodegenerative patients.


Assuntos
Inteligência Artificial , Eletroencefalografia/métodos , Eletroculografia/métodos , Doença de Parkinson/diagnóstico , Doença de Parkinson/fisiopatologia , Polissonografia/métodos , Idoso , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Síndrome da Mioclonia Noturna/diagnóstico , Síndrome da Mioclonia Noturna/fisiopatologia , Análise de Regressão , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador , Fases do Sono/fisiologia
3.
J Neurosci Methods ; 235: 130-7, 2014 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-25016288

RESUMO

BACKGROUND: The golden standard for sleep classification uses manual scoring of polysomnography despite points of criticism such as oversimplification, low inter-rater reliability and the standard being designed on young and healthy subjects. NEW METHOD: To meet the criticism and reveal the latent sleep states, this study developed a general and automatic sleep classifier using a data-driven approach. Spectral EEG and EOG measures and eye correlation in 1s windows were calculated and each sleep epoch was expressed as a mixture of probabilities of latent sleep states by using the topic model Latent Dirichlet Allocation. Model application was tested on control subjects and patients with periodic leg movements (PLM) representing a non-neurodegenerative group, and patients with idiopathic REM sleep behavior disorder (iRBD) and Parkinson's Disease (PD) representing a neurodegenerative group. The model was optimized using 50 subjects and validated on 76 subjects. RESULTS: The optimized sleep model used six topics, and the topic probabilities changed smoothly during transitions. According to the manual scorings, the model scored an overall subject-specific accuracy of 68.3 ± 7.44 (% µ ± σ) and group specific accuracies of 69.0 ± 4.62 (control), 70.1 ± 5.10 (PLM), 67.2 ± 8.30 (iRBD) and 67.7 ± 9.07 (PD). COMPARISON WITH EXISTING METHOD: Statistics of the latent sleep state content showed accordances to the sleep stages defined in the golden standard. However, this study indicates that sleep contains six diverse latent sleep states and that state transitions are continuous processes. CONCLUSIONS: The model is generally applicable and may contribute to the research in neurodegenerative diseases and sleep disorders.


Assuntos
Eletroencefalografia/métodos , Eletroculografia/métodos , Reconhecimento Automatizado de Padrão/métodos , Polissonografia/métodos , Sono/fisiologia , Idoso , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Olho/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome da Mioclonia Noturna/fisiopatologia , Fenômenos Fisiológicos Oculares , Doença de Parkinson/fisiopatologia , Probabilidade , Transtorno do Comportamento do Sono REM/fisiopatologia , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador
4.
Clin Neurophysiol ; 125(3): 512-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24125856

RESUMO

OBJECTIVE: To determine whether sleep spindles (SS) are potentially a biomarker for Parkinson's disease (PD). METHODS: Fifteen PD patients with REM sleep behavior disorder (PD+RBD), 15 PD patients without RBD (PD-RBD), 15 idiopathic RBD (iRBD) patients and 15 age-matched controls underwent polysomnography (PSG). SS were scored in an extract of data from control subjects. An automatic SS detector using a Matching Pursuit (MP) algorithm and a Support Vector Machine (SVM) was developed and applied to the PSG recordings. The SS densities in N1, N2, N3, all NREM combined and REM sleep were obtained and evaluated across the groups. RESULTS: The SS detector achieved a sensitivity of 84.7% and a specificity of 84.5%. At a significance level of α=1%, the iRBD and PD+RBD patients had a significantly lower SS density than the control group in N2, N3 and all NREM stages combined. At a significance level of α=5%, PD-RBD had a significantly lower SS density in N2 and all NREM stages combined. CONCLUSIONS: The lower SS density suggests involvement in pre-thalamic fibers involved in SS generation. SS density is a potential early PD biomarker. SIGNIFICANCE: It is likely that an automatic SS detector could be a supportive diagnostic tool in the evaluation of iRBD and PD patients.


Assuntos
Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Transtorno do Comportamento do Sono REM/etiologia , Transtorno do Comportamento do Sono REM/fisiopatologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Sensibilidade e Especificidade , Sono REM/fisiologia , Tálamo/fisiopatologia
5.
Drug Discov Today ; 19(3): 282-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23954252

RESUMO

Pharmaco-electroencephalography has significant yet unrealised promise as a translatable intermediate biomarker of central pharmacodynamic activity that could help reduce Phase 2 attrition in the development of central nervous system drugs. In an effort to understand its true potential, a framework for decision-making was proposed and the utility of pharmaco-electroencephalography was assessed through several case studies. A key finding was that lack of standardisation reduces the value of data pooling and meta-analyses and renders assessment of translatability difficult, limiting utility in all but simple cases. Pre-competitive collaboration is essential both to improving understanding of translation and developing modern signal processing techniques.


Assuntos
Fármacos do Sistema Nervoso Central/farmacologia , Desenho de Drogas , Eletroencefalografia/métodos , Animais , Biomarcadores , Comportamento Cooperativo , Tomada de Decisões , Humanos , Pesquisa Médica Translacional/métodos
6.
Artigo em Inglês | MEDLINE | ID: mdl-24109718

RESUMO

Patients suffering from the sleep disorder idiopathic rapid-eye-movement sleep behavior disorder (iRBD) have been observed to be in high risk of developing Parkinson's disease (PD). This makes it essential to analyze them in the search for PD biomarkers. This study aims at classifying patients suffering from iRBD or PD based on features reflecting eye movements (EMs) during sleep. A Latent Dirichlet Allocation (LDA) topic model was developed based on features extracted from two electrooculographic (EOG) signals measured as parts in full night polysomnographic (PSG) recordings from ten control subjects. The trained model was tested on ten other control subjects, ten iRBD patients and ten PD patients, obtaining a EM topic mixture diagram for each subject in the test dataset. Three features were extracted from the topic mixture diagrams, reflecting "certainty", "fragmentation" and "stability" in the timely distribution of the EM topics. Using a Naive Bayes (NB) classifier and the features "certainty" and "stability" yielded the best classification result and the subjects were classified with a sensitivity of 95 %, a specificity of 80% and an accuracy of 90 %. This study demonstrates in a data-driven approach, that iRBD and PD patients may exhibit abnorm form and/or timely distribution of EMs during sleep.


Assuntos
Movimentos Oculares , Doença de Parkinson/fisiopatologia , Transtorno do Comportamento do Sono REM/diagnóstico , Transtorno do Comportamento do Sono REM/fisiopatologia , Processamento de Sinais Assistido por Computador , Sono , Idoso , Artefatos , Teorema de Bayes , Estudos de Casos e Controles , Eletroculografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/classificação , Polissonografia , Transtorno do Comportamento do Sono REM/classificação , Sensibilidade e Especificidade
7.
Conf Proc IEEE Eng Med Biol Soc ; 2013: 4275-8, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24110677

RESUMO

Sleep analysis is an important diagnostic tool for sleep disorders. However, the current manual sleep scoring is time-consuming as it is a crude discretization in time and stages. This study changes Esbroeck and Westover's [1] latent sleep staging model into a global model. The proposed data-driven method trained a topic mixture model on 10 control subjects and was applied on 10 other control subjects, 10 iRBD patients and 10 Parkinson's patients. In that way 30 topic mixture diagrams were obtained from which features reflecting distinct sleep architectures between control subjects and patients were extracted. Two features calculated on basis of two latent sleep states classified subjects as "control" or "patient" by a simple clustering algorithm. The mean sleep staging accuracy compared to classical AASM scoring was 72.4% for control subjects and a clustering of the derived features resulted in a sensitivity of 95% and a specificity of 80 %. This study demonstrates that frequency analysis of sleep EEG can be used for data-driven global sleep classification and that topic features separates iRBD and Parkinson's patients from control subjects.


Assuntos
Eletroencefalografia/métodos , Modelos Biológicos , Doença de Parkinson/fisiopatologia , Transtorno do Comportamento do Sono REM/fisiopatologia , Fases do Sono/fisiologia , Algoritmos , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia
8.
Conf Proc IEEE Eng Med Biol Soc ; 2012: 2941-4, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23366541

RESUMO

In this study, polysomnographic left side EOG signals from ten control subjects, ten iRBD patients and ten Parkinson's patients were decomposed in time and frequency using wavelet transformation. A total of 28 features were computed as the means and standard deviations in energy measures from different reconstructed detail subbands across all sleep epochs during a whole night of sleep. A subset of features was chosen based on a cross validated Shrunken Centroids Regularized Discriminant Analysis, where the controls were treated as one group and the patients as another. Classification of the subjects was done by a leave-one-out validation approach using same method, and reached a sensitivity of 95%, a specificity of 70% and an accuracy of 86.7%. It was found that in the optimal subset of features, two hold lower frequencies reflecting the rapid eye movements and two hold higher frequencies reflecting EMG activity. This study demonstrates that both analysis of eye movements during sleep as well as EMG activity measured at the EOG channel hold potential of being biomarkers for Parkinson's disease.


Assuntos
Eletroculografia/métodos , Doença de Parkinson/fisiopatologia , Algoritmos , Eletroencefalografia , Eletromiografia , Humanos , Polissonografia , Análise de Componente Principal , Fases do Sono/fisiologia , Sono REM
9.
PLoS Comput Biol ; 5(3): e1000314, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19300473

RESUMO

Self-organized criticality is an attractive model for human brain dynamics, but there has been little direct evidence for its existence in large-scale systems measured by neuroimaging. In general, critical systems are associated with fractal or power law scaling, long-range correlations in space and time, and rapid reconfiguration in response to external inputs. Here, we consider two measures of phase synchronization: the phase-lock interval, or duration of coupling between a pair of (neurophysiological) processes, and the lability of global synchronization of a (brain functional) network. Using computational simulations of two mechanistically distinct systems displaying complex dynamics, the Ising model and the Kuramoto model, we show that both synchronization metrics have power law probability distributions specifically when these systems are in a critical state. We then demonstrate power law scaling of both pairwise and global synchronization metrics in functional MRI and magnetoencephalographic data recorded from normal volunteers under resting conditions. These results strongly suggest that human brain functional systems exist in an endogenous state of dynamical criticality, characterized by a greater than random probability of both prolonged periods of phase-locking and occurrence of large rapid changes in the state of global synchronization, analogous to the neuronal "avalanches" previously described in cellular systems. Moreover, evidence for critical dynamics was identified consistently in neurophysiological systems operating at frequency intervals ranging from 0.05-0.11 to 62.5-125 Hz, confirming that criticality is a property of human brain functional network organization at all frequency intervals in the brain's physiological bandwidth.


Assuntos
Potenciais de Ação/fisiologia , Relógios Biológicos/fisiologia , Encéfalo/fisiologia , Sincronização Cortical , Modelos Neurológicos , Rede Nervosa/fisiologia , Transmissão Sináptica/fisiologia , Animais , Simulação por Computador , Humanos , Neurônios/fisiologia
10.
J Neurosci ; 27(32): 8643-53, 2007 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-17687042

RESUMO

The hyperpolarization-activated cation current I(h) exhibits a steep gradient of channel density in dendrites of pyramidal neurons, which is associated with location independence of temporal summation of EPSPs at the soma. In striking contrast, here we show by using dendritic patch-clamp recordings that in cerebellar Purkinje cells, the principal neurons of the cerebellar cortex, I(h) exhibits a uniform dendritic density, while location independence of EPSP summation is observed. Using compartmental modeling in realistic and simplified dendritic geometries, we demonstrate that the dendritic distribution of I(h) only weakly affects the degree of temporal summation at the soma, while having an impact at the dendritic input location. We further analyze the effect of I(h) on temporal summation using cable theory and derive bounds for temporal summation for any spatial distribution of I(h). We show that the total number of I(h) channels, not their distribution, governs the degree of temporal summation of EPSPs. Our findings explain the effect of I(h) on EPSP shape and temporal summation, and suggest that neurons are provided with two independent degrees of freedom for different functions: the total amount of I(h) (controlling the degree of temporal summation of dendritic inputs at the soma) and the dendritic spatial distribution of I(h) (regulating local dendritic processing).


Assuntos
Dendritos/fisiologia , Canais de Potássio/fisiologia , Animais , Animais Recém-Nascidos , Canais de Cátion Regulados por Nucleotídeos Cíclicos , Dendritos/química , Potenciais Pós-Sinápticos Excitadores/fisiologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Neurônios/química , Neurônios/fisiologia , Canais de Potássio/análise , Ratos , Ratos Sprague-Dawley
11.
J Physiol ; 539(Pt 2): 469-83, 2002 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-11882679

RESUMO

We investigated the role of the hyperpolarization-activated mixed cation current, I(H), in the control of spontaneous action potential firing of rat cerebellar Purkinje neurons in brain slices. Extracellular recordings revealed that the continual action potential firing of Purkinje neurons was disrupted by the pharmacological blockade of I(H). Blockade of I(H) revealed spontaneous transitions between periods of tonic action potential firing and quiescence, without effects on the frequency or variance of action potential generation. Whole-cell recordings revealed that blockade of I(H) unmasked a form of membrane potential bistability, where transitions between tonic firing and quiescent states (separated by approximately 20 mV) were evoked by excitatory and inhibitory postsynaptic potentials, or by the delivery of brief (20 ms) somatic or dendritic positive and negative current pulses. The stable upper state of tonic action potential firing was maintained by the recruitment of axo-somatic voltage-activated sodium, but not calcium, channels. Negative modulation of I(H) by serotonin unmasked bistability, indicating that bistability of Purkinje neurons is likely to occur under physiological conditions. These data indicate that I(H) acts as a 'safety net', maintaining the membrane potential of Purkinje neurons within the range necessary for the generation of tonic action potential firing. Following the downregulation of I(H), synaptic inhibition can generate long periods (seconds) of quiescence, the duration of which can be controlled by climbing fibre activation and by the underlying 'tone' of parallel fibre activity.


Assuntos
Canais Iônicos/fisiologia , Células de Purkinje/fisiologia , Potenciais de Ação/fisiologia , Animais , Canais de Cátion Regulados por Nucleotídeos Cíclicos , Dendritos/efeitos dos fármacos , Dendritos/metabolismo , Regulação para Baixo/efeitos dos fármacos , Estimulação Elétrica , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Técnicas In Vitro , Masculino , Potenciais da Membrana/fisiologia , Canais de Potássio , Ratos , Ratos Wistar , Serotonina/farmacologia , Sinapses/efeitos dos fármacos
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