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1.
J Vis Exp ; (168)2021 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-33682857

RESUMO

The use of electrocorticographic (ECoG) recordings in rodents is relevant to sleep research and to the study of a wide range of neurological conditions. Adeno-associated viruses (AAVs) are increasingly used to improve understanding of brain circuits and their functions. The AAV-mediated manipulation of specific cell populations and/or of precise molecular components has been tremendously useful to identify new sleep regulatory circuits/molecules and key proteins contributing to the adverse effects of sleep loss. For instance, inhibiting activity of the filamentous actin-severing protein cofilin using AAV prevents sleep deprivation-induced memory impairment. Here, a protocol is described that combines the manipulation of cofilin function in a cerebral cortex area with the recording of ECoG activity to examine whether cortical cofilin modulates the wakefulness and sleep ECoG signals. AAV injection is performed during the same surgical procedure as the implantation of ECoG and electromyographic (EMG) electrodes in adult male and female mice. Mice are anesthetized, and their heads are shaved. After skin cleaning and incision, stereotaxic coordinates of the motor cortex are determined, and the skull is pierced at this location. A cannula prefilled with an AAV expressing cofilinS3D, an inactive form of cofilin, is slowly positioned in the cortical tissue. After AAV infusion, gold-covered screws (ECoG electrodes) are screwed through the skull and cemented to the skull with gold wires inserted in the neck muscles (EMG electrodes). The animals are allowed three weeks to recover and to ensure sufficient expression of cofilinS3D. The infected area and cell type are verified using immunohistochemistry, and the ECoG is analyzed using visual identification of vigilance states and spectral analysis. In summary, this combined methodological approach allows the investigation of the precise contribution of molecular components regulating neuronal morphology and connectivity to the regulation of synchronized cerebral cortex activity during wakefulness and sleep.


Assuntos
Fatores de Despolimerização de Actina/metabolismo , Córtex Cerebral/diagnóstico por imagem , Dependovirus/metabolismo , Eletrocorticografia , Animais , Eletrodos , Eletromiografia , Feminino , Injeções , Masculino , Camundongos Endogâmicos C57BL , Sono/fisiologia , Vigília/fisiologia
2.
Nat Neurosci ; 24(4): 554-564, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33686299

RESUMO

In humans, brain oscillations support critical features of memory formation. However, understanding the molecular mechanisms underlying this activity remains a major challenge. Here, we measured memory-sensitive oscillations using intracranial electroencephalography recordings from the temporal cortex of patients performing an episodic memory task. When these patients subsequently underwent resection, we employed transcriptomics on the temporal cortex to link gene expression with brain oscillations and identified genes correlated with oscillatory signatures of memory formation across six frequency bands. A co-expression analysis isolated oscillatory signature-specific modules associated with neuropsychiatric disorders and ion channel activity, with highly correlated genes exhibiting strong connectivity within these modules. Using single-nucleus transcriptomics, we further revealed that these modules are enriched for specific classes of both excitatory and inhibitory neurons, and immunohistochemistry confirmed expression of highly correlated genes. This unprecedented dataset of patient-specific brain oscillations coupled to genomics unlocks new insights into the genetic mechanisms that support memory encoding.


Assuntos
Memória Episódica , Lobo Temporal/fisiologia , Transcriptoma , Epilepsia Resistente a Medicamentos/cirurgia , Eletrocorticografia , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino
3.
Epilepsia ; 62(2): 481-491, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33332586

RESUMO

OBJECTIVE: This study was undertaken to evaluate the influence that subject-specific factors have on intracranial interictal epileptiform discharge (IED) rates in persons with refractory epilepsy. METHODS: One hundred fifty subjects with intracranial electrodes performed multiple sessions of a free recall memory task; this standardized task controlled for subject attention levels. We utilized a dominance analysis to rank the importance of subject-specific factors based on their relative influence on IED rates. Linear mixed-effects models were employed to comprehensively examine factors with highly ranked importance. RESULTS: Antiseizure medication (ASM) status, time of testing, and seizure onset zone (SOZ) location were the highest-ranking factors in terms of their impact on IED rates. The average IED rate of electrodes in SOZs was 34% higher than the average IED rate of electrodes outside of SOZs (non-SOZ; p < .001). However, non-SOZ electrodes had similar IED rates regardless of the subject's SOZ location (p = .99). Subjects on older generation (p < .001) and combined generation (p < .001) ASM regimens had significantly lower IED rates relative to the group taking no ASMs; newer generation ASM regimens demonstrated a nonsignificant association with IED rates (p = .13). Of the ASMs included in this study, the following ASMs were associated with significant reductions in IED rates: levetiracetam (p < .001), carbamazepine (p < .001), lacosamide (p = .03), zonisamide (p = .01), lamotrigine (p = .03), phenytoin (p = .03), and topiramate (p = .01). We observed a nonsignificant association between time of testing and IED rates (morning-afternoon p = .15, morning-evening p = .85, afternoon-evening p = .26). SIGNIFICANCE: The current study ranks the relative influence that subject-specific factors have on IED rates and highlights the importance of considering certain factors, such as SOZ location and ASM status, when analyzing IEDs for clinical or research purposes.


Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/fisiopatologia , Adulto , Atenção , Carbamazepina/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Eletrocorticografia , Feminino , Humanos , Lacosamida/uso terapêutico , Lamotrigina/uso terapêutico , Levetiracetam/uso terapêutico , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Fenitoína/uso terapêutico , Fatores de Tempo , Topiramato/uso terapêutico , Zonisamida/uso terapêutico
4.
Epilepsia ; 62(2): 371-382, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33377501

RESUMO

OBJECTIVE: Most seizure forecasting algorithms have relied on features specific to electroencephalographic recordings. Environmental and physiological factors, such as weather and sleep, have long been suspected to affect brain activity and seizure occurrence but have not been fully explored as prior information for seizure forecasts in a patient-specific analysis. The study aimed to quantify whether sleep, weather, and temporal factors (time of day, day of week, and lunar phase) can provide predictive prior probabilities that may be used to improve seizure forecasts. METHODS: This study performed post hoc analysis on data from eight patients with a total of 12.2 years of continuous intracranial electroencephalographic recordings (average = 1.5 years, range = 1.0-2.1 years), originally collected in a prospective trial. Patients also had sleep scoring and location-specific weather data. Histograms of future seizure likelihood were generated for each feature. The predictive utility of individual features was measured using a Bayesian approach to combine different features into an overall forecast of seizure likelihood. Performance of different feature combinations was compared using the area under the receiver operating curve. Performance evaluation was pseudoprospective. RESULTS: For the eight patients studied, seizures could be predicted above chance accuracy using sleep (five patients), weather (two patients), and temporal features (six patients). Forecasts using combined features performed significantly better than chance in six patients. For four of these patients, combined forecasts outperformed any individual feature. SIGNIFICANCE: Environmental and physiological data, including sleep, weather, and temporal features, provide significant predictive information on upcoming seizures. Although forecasts did not perform as well as algorithms that use invasive intracranial electroencephalography, the results were significantly above chance. Complementary signal features derived from an individual's historic seizure records may provide useful prior information to augment traditional seizure detection or forecasting algorithms. Importantly, many predictive features used in this study can be measured noninvasively.


Assuntos
Epilepsia/fisiopatologia , Convulsões/epidemiologia , Sono , Fatores de Tempo , Tempo (Meteorologia) , Adulto , Teorema de Bayes , Eletrocorticografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco
5.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 629-632, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018066

RESUMO

Studying the neural correlates of sleep can lead to revelations in our understanding of sleep and its interplay with different neurological disorders. Sleep research relies on manual annotation of sleep stages based on rules developed for healthy adults. Automating sleep stage annotation can expedite sleep research and enable us to better understand atypical sleep patterns. Our goal was to create a fully unsupervised approach to label sleep and wake states in human electro-corticography (ECoG) data from epilepsy patients. Here, we demonstrate that with continuous data from a single ECoG electrode, hidden semi-Markov models (HSMM) perform best in classifying sleep/wake states without excessive transitions, with a mean accuracy (n=4) of 85.2% compared to using K-means clustering (72.2%) and hidden Markov models (81.5%). Our results confirm that HSMMs produce meaningful labels for ECoG data and establish the groundwork to apply this model to cluster sleep stages and potentially other behavioral states.


Assuntos
Eletrocorticografia , Vigília , Adulto , Humanos , Polissonografia , Sono , Fases do Sono
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2524-2527, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018520

RESUMO

Surgical resection of the seizure onset zone (SOZ) could potentially lead to seizure-freedom in medically refractory epilepsy patients. However, localizing the SOZ can be a time consuming and tedious process involving visual inspection of intracranial electroencephalographic (iEEG) recordings captured during passive patient monitoring. Single pulse electrical stimulation (SPES) is currently performed on patients undergoing invasive EEG monitoring for the main purposes of mapping functional brain networks such as language and motor networks. We hypothesize that evoked responses from SPES can also be used to localize the SOZ as they may express the natural frequencies and connectivity of the iEEG network. To test our hypothesis, we construct patient specific single-input multi-output transfer function models from the evoked responses recorded from five epilepsy patients that underwent SPES evaluation and iEEG monitoring. Our preliminary results suggest that the stimulation electrodes that produced the highest gain transfer functions, as measured by the ${\mathcal{H}_\infty }$ norm, correspond to those electrodes clinically defined in the SOZ in successfully treated patients.Clinical Relevance- This study creates an innovative tool that allows clinicians to identify the seizure onset zone in medically refractory epilepsy patients using quantitative metrics thereby increasing surgical success outcomes, mitigating patient risks, and decreasing costs.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Epilepsia Resistente a Medicamentos/terapia , Estimulação Elétrica , Eletrocorticografia , Epilepsia/terapia , Humanos , Convulsões/terapia
7.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2528-2531, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018521

RESUMO

Surgical removal of the seizure onset zone (SOZ) in epilepsy patients is a potentially curative treatment, but the process heavily relies on accurate localization of the SOZ via visual inspection. SPES (Single-pulse electrical stimulation) is a method recently used to explore inter-areal connectivity in vivo to probe functional brain networks such as language and motor networks, and to a much lesser degree, seizure networks. We hypothesized that a dynamical quantification of the connectivity networks derived from the evoked responses induced by SPES could also be used to localize the SOZ. To test our hypothesis, we used an intracranial EEG (iEEG) data set in which five epilepsy patients underwent extensive SPES evaluation. For each patient, and for each dataset that stimulated a different pair of electrodes, we constructed a state-space model from the patient's data. Specifically, we simultaneously estimated model parameters under an exogenous pulse input to a dynamical system whose state vector consisted of the response iEEG signals. Then, the size of the reachable state space, as quantified by the maximum singular value of the reachability matrix, σmax(R), was computed and denoted as the "largest" network response possible when stimulating the given pair. Our results suggest high agreement between σmax(R) and clinically annotated SOZ for patients with localizable SOZs.Clinical Relevance- Our study applies dynamical systems theory to identify epileptogenic brain regions, creating a novel tool that clinicians may use in surgical planning for medically-refractory epilepsy patients.


Assuntos
Epilepsia Resistente a Medicamentos , Convulsões , Animais , Encéfalo , Eletrocorticografia , Potenciais Evocados , Humanos
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3066-3069, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018652

RESUMO

The goal of this study is to estimate the thermal impact of a titanium skull unit (SU) implanted on the exterior aspect of the human skull. We envision this unit to house the front-end of a fully implantable electrocorticogram (ECoG)-based bi-directional (BD) brain-computer interface (BCI). Starting from the bio-heat transfer equation with physiologically and anatomically constrained tissue parameters, we used the finite element method (FEM) implemented in COMSOL to build a computational model of the SU's thermal impact. Based on our simulations, we predicted that the SU could consume up to 75 mW of power without raising the temperature of surrounding tissues above the safe limits (increase in temperature of 1°C). This power budget by far exceeds the power consumption of our front-end prototypes, suggesting that this design can sustain the SU's ability to record ECoG signals and deliver cortical stimulation. These predictions will be used to further refine the existing SU design and inform the design of future SU prototypes.


Assuntos
Interfaces Cérebro-Computador , Eletrocorticografia , Temperatura Alta , Humanos , Próteses e Implantes , Crânio
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 3493-3496, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018756

RESUMO

Electrocorticography (ECoG)-based bi-directional (BD) brain-computer interfaces (BCIs) are a forthcoming technology promising to help restore function to those with motor and sensory deficits. A major problem with this paradigm is that the cortical stimulation necessary to elicit artificial sensation creates strong electrical artifacts that can disrupt BCI operation by saturating recording amplifiers or obscuring useful neural signal. Even with state-of-the-art hardware artifact suppression methods, robust signal processing techniques are still required to suppress residual artifacts that are present at the digital back-end. Herein we demonstrate the effectiveness of a pre-whitening and null projection artifact suppression method using ECoG data recorded during a clinical neurostimulation procedure. Our method achieved a maximum artifact suppression of 21.49 dB and significantly increased the number of artifact-free frequencies in the frequency domain. This performance surpasses that of a more traditional independent component analysis methodology, while retaining a reduced complexity and increased computational efficiency.


Assuntos
Interfaces Cérebro-Computador , Eletrocorticografia , Artefatos , Projeção , Processamento de Sinais Assistido por Computador
10.
Nat Commun ; 11(1): 4014, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782303

RESUMO

Perception reflects not only sensory inputs, but also the endogenous state when these inputs enter the brain. Prior studies show that endogenous neural states influence stimulus processing through non-specific, global mechanisms, such as spontaneous fluctuations of arousal. It is unclear if endogenous activity influences circuit and stimulus-specific processing and behavior as well. Here we use intracranial recordings from 30 pre-surgical epilepsy patients to show that patterns of endogenous activity are related to the strength of trial-by-trial neural tuning in different visual category-selective neural circuits. The same aspects of the endogenous activity that relate to tuning in a particular neural circuit also correlate to behavioral reaction times only for stimuli from the category that circuit is selective for. These results suggest that endogenous activity can modulate neural tuning and influence behavior in a circuit- and stimulus-specific manner, reflecting a potential mechanism by which endogenous neural states facilitate and bias perception.


Assuntos
Rede Nervosa/fisiologia , Córtex Visual/fisiologia , Percepção Visual/fisiologia , Adulto , Eletrocorticografia , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Neurológicos , Reconhecimento Visual de Modelos/fisiologia , Estimulação Luminosa , Tempo de Reação/fisiologia
11.
Nat Hum Behav ; 4(10): 1039-1052, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32632334

RESUMO

Intracranial electrical stimulation (iES) of the human brain has long been known to elicit a remarkable variety of perceptual, motor and cognitive effects, but the functional-anatomical basis of this heterogeneity remains poorly understood. We conducted a whole-brain mapping of iES-elicited effects, collecting first-person reports following iES at 1,537 cortical sites in 67 participants implanted with intracranial electrodes. We found that intrinsic network membership and the principal gradient of functional connectivity strongly predicted the type and frequency of iES-elicited effects in a given brain region. While iES in unimodal brain networks at the base of the cortical hierarchy elicited frequent and simple effects, effects became increasingly rare, heterogeneous and complex in heteromodal and transmodal networks higher in the hierarchy. Our study provides a comprehensive exploration of the relationship between the hierarchical organization of intrinsic functional networks and the causal modulation of human behaviour and experience with iES.


Assuntos
Mapeamento Encefálico/métodos , Córtex Cerebral/fisiologia , Estimulação Elétrica/métodos , Eletrocorticografia/métodos , Lateralidade Funcional/fisiologia , Rede Nervosa/fisiologia , Adulto , Conectoma/métodos , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsias Parciais/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
PLoS Comput Biol ; 16(7): e1007992, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32614826

RESUMO

Understanding how the human brain processes auditory input remains a challenge. Traditionally, a distinction between lower- and higher-level sound features is made, but their definition depends on a specific theoretical framework and might not match the neural representation of sound. Here, we postulate that constructing a data-driven neural model of auditory perception, with a minimum of theoretical assumptions about the relevant sound features, could provide an alternative approach and possibly a better match to the neural responses. We collected electrocorticography recordings from six patients who watched a long-duration feature film. The raw movie soundtrack was used to train an artificial neural network model to predict the associated neural responses. The model achieved high prediction accuracy and generalized well to a second dataset, where new participants watched a different film. The extracted bottom-up features captured acoustic properties that were specific to the type of sound and were associated with various response latency profiles and distinct cortical distributions. Specifically, several features encoded speech-related acoustic properties with some features exhibiting shorter latency profiles (associated with responses in posterior perisylvian cortex) and others exhibiting longer latency profiles (associated with responses in anterior perisylvian cortex). Our results support and extend the current view on speech perception by demonstrating the presence of temporal hierarchies in the perisylvian cortex and involvement of cortical sites outside of this region during audiovisual speech perception.


Assuntos
Córtex Auditivo/fisiologia , Percepção Auditiva , Modelos Neurológicos , Redes Neurais de Computação , Som , Adolescente , Adulto , Mapeamento Encefálico/métodos , Eletrocorticografia , Feminino , Humanos , Masculino , Filmes Cinematográficos , Fonética , Processamento de Sinais Assistido por Computador , Fala/fisiologia , Percepção da Fala , Fatores de Tempo , Adulto Jovem
13.
World Neurosurg ; 139: 750-761, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32689696

RESUMO

The diagnostic and surgical management of epilepsy has made enormous strides over the past 3 decades, concomitant with advances in technology and electrophysiologic understanding of neuronal connectivity. Distinct zones have been identified within this network that each communicate and play a role in the genesis of seizures. Invasive and noninvasive modalities for defining the epileptogenic lesion or region have been able to more accurately determine which patients are optimal candidates for treatment when their seizures are refractory to conventional conservative management. Ablative, palliative, and disconnecting procedures have been developed as alternatives for traditional open resection techniques, and in recent studies, they have shown excellent seizure control and mitigation of complications. In this review, we discuss the evolution of these advancements in the management of epilepsy and provide an overview of current and future neurosurgical therapeutic modalities.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Procedimentos Neurocirúrgicos/métodos , Implantação de Prótese , Técnicas de Ablação , Lobectomia Temporal Anterior , Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/terapia , Eletrocorticografia , Eletroencefalografia , Neuroimagem Funcional , Ablação por Ultrassom Focalizado de Alta Intensidade , Humanos , Neuroestimuladores Implantáveis , Terapia a Laser , Imagem por Ressonância Magnética , Magnetoencefalografia , Tomografia por Emissão de Pósitrons , Radiocirurgia , Procedimento de Encéfalo Dividido , Tomografia Computadorizada de Emissão de Fóton Único , Estimulação do Nervo Vago
14.
World Neurosurg ; 139: 775-788, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32689698

RESUMO

Technical limitations and clinical challenges have historically limited the diagnostic tools and treatment methods available for surgical approaches to the management of epilepsy. By contrast, recent technological innovations in several areas hold significant promise in improving outcomes and decreasing morbidity. We review innovations in the neurosurgical management of epilepsy in several areas, including wireless recording and stimulation systems (particularly responsive neurostimulation [NeuroPace]), conformal electrodes for high-resolution electrocorticography, robot-assisted stereotactic surgery, optogenetics and optical imaging methods, novel positron emission tomography ligands, and new applications of focused ultrasonography. Investigation into genetic causes of and susceptibilities to epilepsy has introduced a new era of precision medicine, enabling the understanding of cell signaling mechanisms underlying epileptic activity as well as patient-specific molecularly targeted treatment options. We discuss the emerging path to individualized treatment plans, predicted outcomes, and improved selection of effective interventions, on the basis of these developments.


Assuntos
Epilepsia Resistente a Medicamentos/cirurgia , Invenções , Procedimentos Neurocirúrgicos , Epilepsia Resistente a Medicamentos/diagnóstico , Epilepsia Resistente a Medicamentos/terapia , Eletrocorticografia , Ablação por Ultrassom Focalizado de Alta Intensidade , Humanos , Neuroestimuladores Implantáveis , Imagem Óptica , Optogenética , Tomografia por Emissão de Pósitrons , Medicina de Precisão , Implantação de Prótese , Procedimentos Cirúrgicos Robóticos , Técnicas Estereotáxicas , Tecnologia sem Fio
15.
Sci Data ; 7(1): 179, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32546753

RESUMO

EEG signal processing is a fundamental method for neurophysiology research and clinical neurology practice. Historically the classification of EEG into physiological, pathological, or artifacts has been performed by expert visual review of the recordings. However, the size of EEG data recordings is rapidly increasing with a trend for higher channel counts, greater sampling frequency, and longer recording duration and complete reliance on visual data review is not sustainable. In this study, we publicly share annotated intracranial EEG data clips from two institutions: Mayo Clinic, MN, USA and St. Anne's University Hospital Brno, Czech Republic. The dataset contains intracranial EEG that are labeled into three groups: physiological activity, pathological/epileptic activity, and artifactual signals. The dataset published here should support and facilitate training of generalized machine learning and digital signal processing methods for intracranial EEG and promote research reproducibility. Along with the data, we also propose a statistical method that is recommended for comparison of candidate classifier performance utilizing out-of-institution/out-of-patient testing.


Assuntos
Artefatos , Encéfalo , Eletrocorticografia , Encéfalo/fisiologia , Encéfalo/fisiopatologia , República Tcheca , Epilepsia/fisiopatologia , Humanos , Aprendizado de Máquina , Minnesota , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador
16.
Epilepsia ; 61(6): e54-e59, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32359085

RESUMO

Organophosphate (OP) compounds constitute a class of highly toxic molecules, characterized by irreversible cholinesterase (ChE) inhibition. Being either pesticides or chemical warfare agents, they present a major health issue in some countries, as well as a terrorist or military threat. Prompted by the need for suitable animal models to test novel medical countermeasures, we developed a new convulsive mouse model of OP poisoning using diisopropylfluorophosphate (DFP). Using electrocorticography (ECoG), we analyzed seizure and status epilepticus (SE) occurrences, as well as relative power of ECoG frequency band modifications after DFP injection in male Swiss mice. Next, we investigated DFP effect on ChE inhibition. Histological changes on neuronal activity and neuronal damage were examined by c-Fos immunolabeling and Fluoro-Jade C staining. We showed that mice exposed to DFP presented electrocorticographic seizures that rapidly progressed to SE within 20 minutes. Lasting >8 hours, DFP-induced SE was associated with major power spectrum modifications in seizing DFP animals compared to control animals. Seizures and SE development were concomitant with profound ChE inhibition and induced massive neuronal degeneration. Presenting all hallmarks of convulsive OP poisoning, we showed that our mouse model is valuable for studying pathophysiological mechanisms and preclinical testing of newly available therapeutic molecules.


Assuntos
Lesões Encefálicas/induzido quimicamente , Modelos Animais de Doenças , Isoflurofato/toxicidade , Organofosfatos/toxicidade , Convulsões/induzido quimicamente , Estado Epiléptico/induzido quimicamente , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/fisiopatologia , Lesões Encefálicas/fisiopatologia , Inibidores da Colinesterase/toxicidade , Eletrocorticografia/efeitos dos fármacos , Eletrocorticografia/métodos , Masculino , Camundongos , Convulsões/fisiopatologia , Estado Epiléptico/fisiopatologia
17.
Proc Natl Acad Sci U S A ; 117(21): 11770-11780, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32398367

RESUMO

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.


Assuntos
Anestesia , Córtex Auditivo , Potenciais Evocados Auditivos , Inconsciência/induzido quimicamente , Anestésicos Intravenosos/farmacologia , Córtex Auditivo/efeitos dos fármacos , Córtex Auditivo/fisiologia , Eletrocorticografia , Potenciais Evocados Auditivos/efeitos dos fármacos , Potenciais Evocados Auditivos/fisiologia , Feminino , Humanos , Masculino , Propofol/farmacologia , Vigília/fisiologia
18.
Proc Natl Acad Sci U S A ; 117(20): 11118-11125, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32358198

RESUMO

Cortical network functioning critically depends on finely tuned interactions to afford neuronal activity propagation over long distances while avoiding runaway excitation. This importance is highlighted by the pathological consequences and impaired performance resulting from aberrant network excitability in psychiatric and neurological diseases, such as epilepsy. Theory and experiment suggest that the control of activity propagation by network interactions can be adequately described by a branching process. This hypothesis is partially supported by strong evidence for balanced spatiotemporal dynamics observed in the cerebral cortex; however, evidence of a causal relationship between network interactions and cortex activity, as predicted by a branching process, is missing in humans. Here this cause-effect relationship is tested by monitoring cortex activity under systematic pharmacological reduction of cortical network interactions with antiepileptic drugs. This study reports that cortical activity cascades, presented by the propagating patterns of epileptic spikes, as well as temporal correlations decline precisely as predicted for a branching process. The results provide a missing link to the branching process theory of cortical network function with implications for understanding the foundations of cortical excitability and its monitoring in conditions like epilepsy.


Assuntos
Anticonvulsivantes/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Rede Nervosa/efeitos dos fármacos , Rede Nervosa/metabolismo , Eletrocorticografia , Epilepsia , Humanos , Redes Neurais de Computação , Neurônios/fisiologia
19.
Nat Commun ; 11(1): 2172, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32358560

RESUMO

The human brain has the capacity to rapidly change state, and in epilepsy these state changes can be catastrophic, resulting in loss of consciousness, injury and even death. Theoretical interpretations considering the brain as a dynamical system suggest that prior to a seizure, recorded brain signals may exhibit critical slowing down, a warning signal preceding many critical transitions in dynamical systems. Using long-term intracranial electroencephalography (iEEG) recordings from fourteen patients with focal epilepsy, we monitored key signatures of critical slowing down prior to seizures. The metrics used to detect critical slowing down fluctuated over temporally long scales (hours to days), longer than would be detectable in standard clinical evaluation settings. Seizure risk was associated with a combination of these signals together with epileptiform discharges. These results provide strong validation of theoretical models and demonstrate that critical slowing down is a reliable indicator that could be used in seizure forecasting algorithms.


Assuntos
Encéfalo/fisiopatologia , Epilepsias Parciais/diagnóstico , Convulsões/diagnóstico , Algoritmos , Biomarcadores , Eletrocorticografia , Humanos , Modelos Neurológicos , Fatores de Risco
20.
PLoS One ; 15(5): e0232530, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32384091

RESUMO

BACKGROUND: Clinical and animal studies have found that anxiety and depression are significantly more common after acute myocardial infarction (AMI). The medial prefrontal cortex (PFC) has a dual role: in higher brain functions and in cardiovascular control, making it a logical candidate for explaining the perceived bidirectional heart-brain connection. We used parallel Electrocardiography (ECG) and Electrocorticography (ECoG) registration to investigate AMI-induced changes in medial PFC bioelectrical activity in a rat model of AMI. MATERIALS AND METHODS: Adult male Wistar albino rats were used in the study. Gold-plated recording electrodes were implanted over the frontal cortex for ECoG recording. ECG was recorded via two holter electrodes attached on the skin of the back fixed in place by a jacket. Induction of AMI was performed by isoprenaline (150 mg/kg, i.p.). ECoG and ECG signals were registered at baseline, during 3 hours after isoprenaline administration and at 24 hours after isoprenaline administration. RESULTS: Significant increases of theta, alpha, and beta electroencephalographic (EEG) band power were observed in different time intervals after isoprenaline administration. Significant increase of theta band peak frequency was also observed during the first hour after isoprenaline administration. No statistically significant differences in band-power activity were found between the pre-isoprenaline measurements and 24 hours after administration. CONCLUSION: Our results demonstrate significant increases in EEG band power of alpha beta and theta bands during isoprenaline-induced AMI model. These are the first findings to connect heart damage during isoprenaline- induced AMI to disturbances in the cortical bioelectrical activity.


Assuntos
Isoproterenol/farmacologia , Infarto do Miocárdio/fisiopatologia , Córtex Pré-Frontal/fisiopatologia , Animais , Ondas Encefálicas/fisiologia , Modelos Animais de Doenças , Eletrocardiografia , Eletrocorticografia , Eletroencefalografia , Masculino , Infarto do Miocárdio/induzido quimicamente , Ratos , Ratos Wistar
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