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1.
Sci Rep ; 12(1): 20011, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414694

RESUMO

CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47-0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity.


Assuntos
Neoplasias Hematológicas , Síndromes Neurotóxicas , Receptores de Antígenos Quiméricos , Humanos , Recidiva Local de Neoplasia , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Eletroencefalografia , Biomarcadores
2.
J Neurosci ; 42(25): 5007-5020, 2022 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-35589391

RESUMO

Consolidation of memory is believed to involve offline replay of neural activity. While amply demonstrated in rodents, evidence for replay in humans, particularly regarding motor memory, is less compelling. To determine whether replay occurs after motor learning, we sought to record from motor cortex during a novel motor task and subsequent overnight sleep. A 36-year-old man with tetraplegia secondary to cervical spinal cord injury enrolled in the ongoing BrainGate brain-computer interface pilot clinical trial had two 96-channel intracortical microelectrode arrays placed chronically into left precentral gyrus. Single- and multi-unit activity was recorded while he played a color/sound sequence matching memory game. Intended movements were decoded from motor cortical neuronal activity by a real-time steady-state Kalman filter that allowed the participant to control a neurally driven cursor on the screen. Intracortical neural activity from precentral gyrus and 2-lead scalp EEG were recorded overnight as he slept. When decoded using the same steady-state Kalman filter parameters, intracortical neural signals recorded overnight replayed the target sequence from the memory game at intervals throughout at a frequency significantly greater than expected by chance. Replay events occurred at speeds ranging from 1 to 4 times as fast as initial task execution and were most frequently observed during slow-wave sleep. These results demonstrate that recent visuomotor skill acquisition in humans may be accompanied by replay of the corresponding motor cortex neural activity during sleep.SIGNIFICANCE STATEMENT Within cortex, the acquisition of information is often followed by the offline recapitulation of specific sequences of neural firing. Replay of recent activity is enriched during sleep and may support the consolidation of learning and memory. Using an intracortical brain-computer interface, we recorded and decoded activity from motor cortex as a human research participant performed a novel motor task. By decoding neural activity throughout subsequent sleep, we find that neural sequences underlying the recently practiced motor task are repeated throughout the night, providing direct evidence of replay in human motor cortex during sleep. This approach, using an optimized brain-computer interface decoder to characterize neural activity during sleep, provides a framework for future studies exploring replay, learning, and memory.


Assuntos
Aprendizagem/fisiologia , Córtex Motor/fisiologia , Sono/fisiologia , Adulto , Interfaces Cérebro-Computador , Vértebras Cervicais , Eletroencefalografia/métodos , Humanos , Masculino , Projetos Piloto , Quadriplegia/etiologia , Quadriplegia/fisiopatologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia
3.
Crit Care Explor ; 4(1): e0611, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35072078

RESUMO

To develop a physiologic grading system for the severity of acute encephalopathy manifesting as delirium or coma, based on EEG, and to investigate its association with clinical outcomes. DESIGN: This prospective, single-center, observational cohort study was conducted from August 2015 to December 2016 and October 2018 to December 2019. SETTING: Academic medical center, all inpatient wards. PATIENTS/SUBJECTS: Adult inpatients undergoing a clinical EEG recording; excluded if deaf, severely aphasic, developmentally delayed, non-English speaking (if noncomatose), or if goals of care focused primarily on comfort measures. Four-hundred six subjects were assessed; two were excluded due to technical EEG difficulties. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A machine learning model, with visually coded EEG features as inputs, was developed to produce scores that correlate with behavioral assessments of delirium severity (Confusion Assessment Method-Severity [CAM-S] Long Form [LF] scores) or coma; evaluated using Spearman R correlation; area under the receiver operating characteristic curve (AUC); and calibration curves. Associations of Visual EEG Confusion Assessment Method Severity (VE-CAM-S) were measured for three outcomes: functional status at discharge (via Glasgow Outcome Score [GOS]), inhospital mortality, and 3-month mortality. Four-hundred four subjects were analyzed (mean [sd] age, 59.8 yr [17.6 yr]; 232 [57%] male; 320 [79%] White; 339 [84%] non-Hispanic); 132 (33%) without delirium or coma, 143 (35%) with delirium, and 129 (32%) with coma. VE-CAM-S scores correlated strongly with CAM-S scores (Spearman correlation 0.67 [0.62-0.73]; p < 0.001) and showed excellent discrimination between levels of delirium (CAM-S LF = 0 vs ≥ 4, AUC 0.85 [0.78-0.92], calibration slope of 1.04 [0.87-1.19] for CAM-S LF ≤ 4 vs ≥ 5). VE-CAM-S scores were strongly associated with important clinical outcomes including inhospital mortality (AUC 0.79 [0.72-0.84]), 3-month mortality (AUC 0.78 [0.71-0.83]), and GOS at discharge (0.76 [0.69-0.82]). CONCLUSIONS: VE-CAM-S is a physiologic grading scale for the severity of symptoms in the setting of delirium and coma, based on visually assessed electroencephalography features. VE-CAM-S scores are strongly associated with clinical outcomes.

4.
Crit Care Med ; 50(1): e11-e19, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34582420

RESUMO

OBJECTIVES: Delirium is a common and frequently underdiagnosed complication in acutely hospitalized patients, and its severity is associated with worse clinical outcomes. We propose a physiologically based method to quantify delirium severity as a tool that can help close this diagnostic gap: the Electroencephalographic Confusion Assessment Method Severity Score (E-CAM-S). DESIGN: Retrospective cohort study. SETTING: Single-center tertiary academic medical center. PATIENTS: Three-hundred seventy-three adult patients undergoing electroencephalography to evaluate altered mental status between August 2015 and December 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We developed the E-CAM-S based on a learning-to-rank machine learning model of forehead electroencephalography signals. Clinical delirium severity was assessed using the Confusion Assessment Method Severity (CAM-S). We compared associations of E-CAM-S and CAM-S with hospital length of stay and inhospital mortality. E-CAM-S correlated with clinical CAM-S (R = 0.67; p < 0.0001). For the overall cohort, E-CAM-S and CAM-S were similar in their strength of association with hospital length of stay (correlation = 0.31 vs 0.41, respectively; p = 0.082) and inhospital mortality (area under the curve = 0.77 vs 0.81; p = 0.310). Even when restricted to noncomatose patients, E-CAM-S remained statistically similar to CAM-S in its association with length of stay (correlation = 0.37 vs 0.42, respectively; p = 0.188) and inhospital mortality (area under the curve = 0.83 vs 0.74; p = 0.112). In addition to previously appreciated spectral features, the machine learning framework identified variability in multiple measures over time as important features in electroencephalography-based prediction of delirium severity. CONCLUSIONS: The E-CAM-S is an automated, physiologic measure of delirium severity that predicts clinical outcomes with a level of performance comparable to conventional interview-based clinical assessment.


Assuntos
Confusão/diagnóstico , Delírio/diagnóstico , Eletroencefalografia/métodos , Processamento de Imagem Assistida por Computador/métodos , Aprendizado de Máquina , Centros Médicos Acadêmicos/estatística & dados numéricos , Adulto , Idoso , Comorbidade , Feminino , Mortalidade Hospitalar/tendências , Hospitais/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença
5.
J Stroke Cerebrovasc Dis ; 31(3): 106270, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34954599

RESUMO

OBJECTIVES: Delirium is common among patients with acute stroke and associated with worse outcomes. However, it is unclear which stroke locations or types are most associated with delirium. MATERIALS AND METHODS: We systematically reviewed studies of patients with acute stroke that reported stroke locations and types by delirium status. We included papers in any language, through a combined search from January 2010 to June 2021. Case studies with less than 20 patients, case-control studies, and randomized controlled trials were excluded. MEDLINE, EMBASE, PsycINFO, CINAHL, and Alois databases were searched. Pooled relative risks were calculated using bivariate random effects models or network meta-analysis. Methodological quality was assessed across 8 factors. RESULTS: 31 patient samples representing 8329 patients were included. Delirium was more common in patients with supratentorial lesions than infratentorial (RR [Relative Risk] 2.01, CI [Confidence Interval] 1.49-2.72); anterior circulation lesions than posterior (RR 1.41, CI 1.13-1.78); and cortical lesions than subcortical (RR 1.54, CI 1.25-1.89). Stroke side was not associated with delirium (right vs. left: RR 0.99, CI 0.77-1.28). Delirium was more common in patients with hemorrhagic strokes than ischemic (RR 1.74, CI 1.42-2.11) and patients with preexisting qualitative atrophy (RR 1.66, CI 1.21-2.27). CONCLUSION: Several brain localizations and types of strokes were associated with delirium. Conclusions were in part limited by the heterogeneity of studies and broad or qualitative lesion descriptions. These results may assist in anticipating the risk of delirium in acute stroke and highlight brain networks and pathologies that may be involved in the pathophysiology of delirium.


Assuntos
Delírio , Acidente Vascular Cerebral , Delírio/epidemiologia , Humanos , Metanálise em Rede , Risco , Acidente Vascular Cerebral/epidemiologia
6.
PLoS One ; 16(12): e0259840, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34855749

RESUMO

BACKGROUND: We investigated the effect of delirium burden in mechanically ventilated patients, beginning in the ICU and continuing throughout hospitalization, on functional neurologic outcomes up to 2.5 years following critical illness. METHODS: Prospective cohort study of enrolling 178 consecutive mechanically ventilated adult medical and surgical ICU patients between October 2013 and May 2016. Altogether, patients were assessed daily for delirium 2941days using the Confusion Assessment Method for the ICU (CAM-ICU). Hospitalization delirium burden (DB) was quantified as number of hospital days with delirium divided by total days at risk. Survival status up to 2.5 years and neurologic outcomes using the Glasgow Outcome Scale were recorded at discharge 3, 6, and 12 months post-discharge. RESULTS: Of 178 patients, 19 (10.7%) were excluded from outcome analyses due to persistent coma. Among the remaining 159, 123 (77.4%) experienced delirium. DB was independently associated with >4-fold increased mortality at 2.5 years following ICU admission (adjusted hazard ratio [aHR], 4.77; 95% CI, 2.10-10.83; P < .001), and worse neurologic outcome at discharge (adjusted odds ratio [aOR], 0.02; 0.01-0.09; P < .001), 3 (aOR, 0.11; 0.04-0.31; P < .001), 6 (aOR, 0.10; 0.04-0.29; P < .001), and 12 months (aOR, 0.19; 0.07-0.52; P = .001). DB in the ICU alone was not associated with mortality (HR, 1.79; 0.93-3.44; P = .082) and predicted neurologic outcome less strongly than entire hospital stay DB. Similarly, the number of delirium days in the ICU and for whole hospitalization were not associated with mortality (HR, 1.00; 0.93-1.08; P = .917 and HR, 0.98; 0.94-1.03, P = .535) nor with neurological outcomes, except for the association between ICU delirium days and neurological outcome at discharge (OR, 0.90; 0.81-0.99, P = .038). CONCLUSIONS: Delirium burden throughout hospitalization independently predicts long term neurologic outcomes and death up to 2.5 years after critical illness, and is more predictive than delirium burden in the ICU alone and number of delirium days.


Assuntos
Delírio/mortalidade , Delírio/fisiopatologia , Unidades de Terapia Intensiva , Idoso , Analgésicos/uso terapêutico , Coma/mortalidade , Coma/fisiopatologia , Estado Terminal/mortalidade , Feminino , Seguimentos , Humanos , Hipnóticos e Sedativos/uso terapêutico , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/etiologia , Prevalência , Estudos Prospectivos , Respiração Artificial
7.
Elife ; 102021 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821218

RESUMO

Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its rostrocaudal axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from rostral and caudal BFCNs over a 1-month period of variable reinforcement learning in mice. BFCNs in both regions showed equivalently weak responses to unconditioned visual stimuli and anticipated rewards. Rostral BFCNs in the horizontal limb of the diagonal band were more responsive to reward omission, more accurately classified behavioral outcomes, and more closely tracked fluctuations in pupil-indexed global brain state. Caudal tail BFCNs in globus pallidus and substantia innominata were more responsive to unconditioned auditory stimuli, orofacial movements, aversive reinforcement, and showed robust associative plasticity for punishment-predicting cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.


Assuntos
Prosencéfalo Basal/fisiologia , Neurônios Colinérgicos/fisiologia , Condicionamento Clássico/fisiologia , Sinais (Psicologia) , Camundongos/fisiologia , Animais , Feminino , Masculino , Reforço Psicológico
8.
Semin Neurol ; 41(5): 572-587, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34619782

RESUMO

Delirium, sometimes referred to as encephalopathy, is an acute confusional state that is both common in hospitalized patients and associated with poor outcomes. For patients, families, and caregivers, delirium can be a traumatic experience. While delirium is one of the most common diagnoses encountered by the consulting neurologist, the majority of the time it will have been previously unrecognized as such by the care team. Neurologic syndromes such as dementia or aphasia can either be misdiagnosed as delirium or may coexist with it, necessitating careful neurologic assessment. Once the diagnosis of delirium has been established, a careful evaluation for predisposing and precipitating factors can help uncover modifiable contributors, which should be addressed as part of a multicomponent, primarily nonpharmacologic intervention. Importantly, delirium management, which begins with comprehensive prevention, should emphasize the humanity of the delirious patient and the challenges of caring for this vulnerable population. When considered, delirium represents an important opportunity for the neurologist to substantially enhance patient care.


Assuntos
Delírio , Delírio/diagnóstico , Delírio/terapia , Humanos
9.
Neurohospitalist ; 11(3): 204-213, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34163546

RESUMO

BACKGROUND AND PURPOSE: Reports have suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes neurologic manifestations including encephalopathy and seizures. However, there has been relatively limited electrophysiology data to contextualize these specific concerns and to understand their associated clinical factors. Our objective was to identify EEG abnormalities present in patients with SARS-CoV-2, and to determine whether they reflect new or preexisting brain pathology. METHODS: We studied a consecutive series of hospitalized patients with SARS-CoV-2 who received an EEG, obtained using tailored safety protocols. Data from EEG reports and clinical records were analyzed to identify EEG abnormalities and possible clinical associations, including neurologic symptoms, new or preexisting brain pathology, and sedation practices. RESULTS: We identified 37 patients with SARS-CoV-2 who underwent EEG, of whom 14 had epileptiform findings (38%). Patients with epileptiform findings were more likely to have preexisting brain pathology (6/14, 43%) than patients without epileptiform findings (2/23, 9%; p = 0.042). There were no clear differences in rates of acute brain pathology. One case of nonconvulsive status epilepticus was captured, but was not clearly a direct consequence of SARS-CoV-2. Abnormalities of background rhythms were common, as may be seen in systemic illness, and in part associated with recent sedation (p = 0.022). CONCLUSIONS: Epileptiform abnormalities were common in patients with SARS-CoV-2 referred for EEG, but particularly in the context of preexisting brain pathology and sedation. These findings suggest that neurologic manifestations during SARS-CoV-2 infection may not solely relate to the infection itself, but rather may also reflect patients' broader, preexisting neurologic vulnerabilities.

10.
Ann Neurol ; 89(5): 872-883, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33704826

RESUMO

OBJECTIVE: The aim was to determine the prevalence and risk factors for electrographic seizures and other electroencephalographic (EEG) patterns in patients with Coronavirus disease 2019 (COVID-19) undergoing clinically indicated continuous electroencephalogram (cEEG) monitoring and to assess whether EEG findings are associated with outcomes. METHODS: We identified 197 patients with COVID-19 referred for cEEG at 9 participating centers. Medical records and EEG reports were reviewed retrospectively to determine the incidence of and clinical risk factors for seizures and other epileptiform patterns. Multivariate Cox proportional hazards analysis assessed the relationship between EEG patterns and clinical outcomes. RESULTS: Electrographic seizures were detected in 19 (9.6%) patients, including nonconvulsive status epilepticus (NCSE) in 11 (5.6%). Epileptiform abnormalities (either ictal or interictal) were present in 96 (48.7%). Preceding clinical seizures during hospitalization were associated with both electrographic seizures (36.4% in those with vs 8.1% in those without prior clinical seizures, odds ratio [OR] 6.51, p = 0.01) and NCSE (27.3% vs 4.3%, OR 8.34, p = 0.01). A pre-existing intracranial lesion on neuroimaging was associated with NCSE (14.3% vs 3.7%; OR 4.33, p = 0.02). In multivariate analysis of outcomes, electrographic seizures were an independent predictor of in-hospital mortality (hazard ratio [HR] 4.07 [1.44-11.51], p < 0.01). In competing risks analysis, hospital length of stay increased in the presence of NCSE (30 day proportion discharged with vs without NCSE: HR 0.21 [0.03-0.33] vs 0.43 [0.36-0.49]). INTERPRETATION: This multicenter retrospective cohort study demonstrates that seizures and other epileptiform abnormalities are common in patients with COVID-19 undergoing clinically indicated cEEG and are associated with adverse clinical outcomes. ANN NEUROL 2021;89:872-883.


Assuntos
COVID-19/epidemiologia , COVID-19/fisiopatologia , Eletroencefalografia/tendências , Convulsões/epidemiologia , Convulsões/fisiopatologia , Idoso , COVID-19/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Convulsões/diagnóstico , Resultado do Tratamento
12.
eNeuro ; 7(5)2020.
Artigo em Inglês | MEDLINE | ID: mdl-33060183

RESUMO

In vivo electrophysiology experiments require the collection of data from multiple subjects, often for extended periods. Studying multiple subjects for extended periods can be made more efficient through simultaneous recordings, but scaling up recordings to accommodate larger numbers of subjects simultaneously requires coordination and consideration of costs and flexibility. To facilitate this process, we have developed OpBox, an open source set of tools to acquire electroencephalography (EEG) and electromyography (EMG) flexibly from multiple rodent subjects simultaneously. OpBox combines open source hardware and software with off-the-shelf components to create a system that costs less than commercial solutions ($500 per subject), and can be easily deployed for multiple subjects. Coded in MATLAB, OpBox scripts can simultaneously and flexibly collect and display multiple analog and digital data streams, for instance real-time EEG and EMG, event triggers from a behavioral system, and rotary encoder data. OpBox also calculates and displays real-time spectral representations and event-related potentials (ERPs). To verify the performance of our system, we compare our amplifiers with two other commercial amplifiers, a Grass P55 AC preamplifier and an Intan RHD2000-series amplifier. The OpBox amplifier performs comparably to commercial amplifiers for signal-to-noise ratios (SNRs), noise floors, and common mode rejection. We also demonstrate that our acquisition system can reliably record multichannel data from multiple subjects, and has been successfully tested with 12 subjects running simultaneously on a single standard desktop computer. Together, OpBox increases the flexibility and lowers the cost for simultaneous acquisition of electrophysiology data from multiple subjects.


Assuntos
Eletroencefalografia , Software , Eletromiografia , Potenciais Evocados , Processamento de Sinais Assistido por Computador , Razão Sinal-Ruído
13.
Mov Disord Clin Pract ; 7(6): 713-715, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32775525
14.
Epilepsia ; 61(9): 1906-1918, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32761902

RESUMO

OBJECTIVE: Seizure detection is a major facet of electroencephalography (EEG) analysis in neurocritical care, epilepsy diagnosis and management, and the instantiation of novel therapies such as closed-loop stimulation or optogenetic control of seizures. It is also of increased importance in high-throughput, robust, and reproducible pre-clinical research. However, seizure detectors are not widely relied upon in either clinical or research settings due to limited validation. In this study, we create a high-performance seizure-detection approach, validated in multiple data sets, with the intention that such a system could be available to users for multiple purposes. METHODS: We introduce a generalized linear model trained on 141 EEG signal features for classification of seizures in continuous EEG for two data sets. In the first (Focal Epilepsy) data set consisting of 16 rats with focal epilepsy, we collected 1012 spontaneous seizures over 3 months of 24/7 recording. We trained a generalized linear model on the 141 features representing 20 feature classes, including univariate and multivariate, linear and nonlinear, time, and frequency domains. We tested performance on multiple hold-out test data sets. We then used the trained model in a second (Multifocal Epilepsy) data set consisting of 96 rats with 2883 spontaneous multifocal seizures. RESULTS: From the Focal Epilepsy data set, we built a pooled classifier with an Area Under the Receiver Operating Characteristic (AUROC) of 0.995 and leave-one-out classifiers with an AUROC of 0.962. We validated our method within the independently constructed Multifocal Epilepsy data set, resulting in a pooled AUROC of 0.963. We separately validated a model trained exclusively on the Focal Epilepsy data set and tested on the held-out Multifocal Epilepsy data set with an AUROC of 0.890. Latency to detection was under 5 seconds for over 80% of seizures and under 12 seconds for over 99% of seizures. SIGNIFICANCE: This method achieves the highest performance published for seizure detection on multiple independent data sets. This method of seizure detection can be applied to automated EEG analysis pipelines as well as closed loop interventional approaches, and can be especially useful in the setting of research using animals in which there is an increased need for standardization and high-throughput analysis of large number of seizures.


Assuntos
Eletrocorticografia/métodos , Epilepsias Parciais/diagnóstico , Aprendizado de Máquina , Convulsões/diagnóstico , Processamento de Sinais Assistido por Computador , Animais , Área Sob a Curva , Modelos Animais de Doenças , Eletroencefalografia , Epilepsias Parciais/fisiopatologia , Agonistas de Aminoácidos Excitatórios/toxicidade , Ácido Caínico/toxicidade , Modelos Lineares , Curva ROC , Ratos , Reprodutibilidade dos Testes , Convulsões/induzido quimicamente , Convulsões/fisiopatologia
15.
medRxiv ; 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32699855

RESUMO

Background and Purpose Reports have suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes neurologic manifestations including encephalopathy and seizures. However, there has been relatively limited electrophysiology data to contextualize these specific concerns and to understand their associated clinical factors. Our objective was to identify EEG abnormalities present in patients with SARS-CoV-2, and to determine whether they reflect new or preexisting brain pathology. Methods We studied a consecutive series of hospitalized patients with SARS-CoV-2 who received an EEG, obtained using tailored safety protocols. Data from EEG reports and clinical records were analyzed to identify EEG abnormalities and possible clinical associations, including neurologic symptoms, new or preexisting brain pathology, and sedation practices. Results We identified 37 patients with SARS-CoV-2 who underwent EEG, of whom 14 had epileptiform findings (38%). Patients with epileptiform findings were more likely to have preexisting brain pathology (6/14, 43%) than patients without epileptiform findings (2/23, 9%; p=0.042). There were no clear differences in rates of acute brain pathology. One case of nonconvulsive status epilepticus was captured, but was not clearly a direct consequence of SARS-CoV-2. Abnormalities of background rhythms were common, and patients recently sedated were more likely to lack a posterior dominant rhythm (p=0.022). Conclusions Epileptiform abnormalities were common in patients with SARS-CoV-2 referred for EEG, but particularly in the context of preexisting brain pathology and sedation. These findings suggest that neurologic manifestations during SARS-CoV-2 infection may not solely relate to the infection itself, but rather may also reflect patients' broader, preexisting neurologic vulnerabilities.

16.
Science ; 366(6468): 1008-1012, 2019 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-31754002

RESUMO

What individual differences in neural activity predict the future escalation of alcohol drinking from casual to compulsive? The neurobiological mechanisms that gate the transition from moderate to compulsive drinking remain poorly understood. We longitudinally tracked the development of compulsive drinking across a binge-drinking experience in male mice. Binge drinking unmasked individual differences, revealing latent traits in alcohol consumption and compulsive drinking despite equal prior exposure to alcohol. Distinct neural activity signatures of cortical neurons projecting to the brainstem before binge drinking predicted the ultimate emergence of compulsivity. Mimicry of activity patterns that predicted drinking phenotypes was sufficient to bidirectionally modulate drinking. Our results provide a mechanistic explanation for individual variance in vulnerability to compulsive alcohol drinking.


Assuntos
Consumo de Bebidas Alcoólicas , Consumo Excessivo de Bebidas Alcoólicas , Tronco Encefálico/fisiologia , Comportamento Compulsivo , Neurônios/fisiologia , Substância Cinzenta Periaquedutal/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais/fisiologia , Quinina/administração & dosagem
17.
Neurology ; 93(13): e1260-e1271, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31467255

RESUMO

OBJECTIVE: To determine which findings on routine clinical EEGs correlate with delirium severity across various presentations and to determine whether EEG findings independently predict important clinical outcomes. METHODS: We prospectively studied a cohort of nonintubated inpatients undergoing EEG for evaluation of altered mental status. Patients were assessed for delirium within 1 hour of EEG with the 3-Minute Diagnostic Interview for Confusion Assessment Method (3D-CAM) and 3D-CAM severity score. EEGs were interpreted clinically by neurophysiologists, and reports were reviewed to identify features such as theta or delta slowing and triphasic waves. Generalized linear models were used to quantify associations among EEG findings, delirium, and clinical outcomes, including length of stay, Glasgow Outcome Scale scores, and mortality. RESULTS: We evaluated 200 patients (median age 60 years, IQR 48.5-72 years); 121 (60.5%) met delirium criteria. The EEG finding most strongly associated with delirium presence was a composite of generalized theta or delta slowing (odds ratio 10.3, 95% confidence interval 5.3-20.1). The prevalence of slowing correlated not only with overall delirium severity (R 2 = 0.907) but also with the severity of each feature assessed by CAM-based delirium algorithms. Slowing was common in delirium even with normal arousal. EEG slowing was associated with longer hospitalizations, worse functional outcomes, and increased mortality, even after adjustment for delirium presence or severity. CONCLUSIONS: Generalized slowing on routine clinical EEG strongly correlates with delirium and may be a valuable biomarker for delirium severity. In addition, generalized EEG slowing should trigger elevated concern for the prognosis of patients with altered mental status.


Assuntos
Delírio/fisiopatologia , Delírio/terapia , Eletroencefalografia , Índice de Gravidade de Doença , Adulto , Idoso , Algoritmos , Estudos de Coortes , Eletroencefalografia/métodos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Nature ; 563(7731): 397-401, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30405240

RESUMO

Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions1,2; however, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons3-6, where neural activity conveying sensory information (signal) is amplified relative to spontaneous firing (noise). Here we demonstrate that dopamine increases the signal-to-noise ratio of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal grey (dPAG). Using an electrochemical approach, we reveal the precise time course of pinch-evoked dopamine release in the mPFC, and show that mPFC dopamine biases behavioural responses to aversive stimuli. Activation of mPFC-dPAG neurons is sufficient to drive place avoidance and defensive behaviours. mPFC-dPAG neurons display robust shock-induced excitations, as visualized by single-cell, projection-defined microendoscopic calcium imaging. Finally, photostimulation of dopamine terminals in the mPFC reveals an increase in the signal-to-noise ratio in mPFC-dPAG responses to aversive stimuli. Together, these data highlight how dopamine in the mPFC can selectively route sensory information to specific downstream circuits, representing a potential circuit mechanism for valence processing.


Assuntos
Aprendizagem da Esquiva/fisiologia , Dopamina/metabolismo , Substância Cinzenta Periaquedutal/citologia , Substância Cinzenta Periaquedutal/fisiologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/fisiologia , Animais , Sinalização do Cálcio , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Vias Neurais , Ratos , Ratos Long-Evans , Razão Sinal-Ruído , Análise de Célula Única , Cauda
19.
J Am Med Dir Assoc ; 18(12): 1010-1018.e1, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28927945

RESUMO

OBJECTIVES: To survey the current methods used to ascertain dementia and mild cognitive impairment (MCI) in longitudinal cohort studies, to categorize differences in approaches and to identify key components of expert panel methodology in current use. METHODS: We searched PubMed for the past 10 years, from March 6, 2007 to March 6, 2017 using a combination of controlled vocabulary and keyword terms to identify expert panel consensus methods used to diagnose MCI or dementia in large cohort studies written in English. From these results, we identified a framework for reporting standards and describe as an exemplar the clinical consensus procedure used in an ongoing study of elective surgery patients (the Successful Aging after Elective Surgery study). RESULTS: Thirty-one articles representing unique cohorts were included. Among published methods, membership of experts panel varied significantly. There was more similarity in what types of information was use to ascertain disease status. However, information describing the diagnostic decision process and resolution of disagreements was often lacking. CONCLUSIONS: Methods used for expert panel diagnosis of MCI and dementia in large cohort studies are widely variable, and there is a need for more standardized reporting of these approaches. By describing the procedure in which our expert panel achieved consensus diagnoses, we hope to encourage the development and publication of well-founded and reproducible methods for diagnosis of MCI and dementia in longitudinal studies.


Assuntos
Envelhecimento/fisiologia , Doença de Alzheimer/epidemiologia , Disfunção Cognitiva/epidemiologia , Procedimentos Cirúrgicos Eletivos/psicologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Consenso , Progressão da Doença , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Avaliação Geriátrica/métodos , Humanos , Incidência , Estudos Longitudinais , Masculino , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Estados Unidos/epidemiologia
20.
Nat Neurosci ; 20(6): 824-835, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28436980

RESUMO

Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock- and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.


Assuntos
Tonsila do Cerebelo/fisiologia , Córtex Pré-Frontal/fisiologia , Punição , Recompensa , 2-Amino-5-fosfonovalerato/administração & dosagem , 2-Amino-5-fosfonovalerato/farmacologia , Potenciais de Ação/fisiologia , Animais , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Sinais (Psicologia) , Discriminação Psicológica/efeitos dos fármacos , Discriminação Psicológica/fisiologia , Estimulação Elétrica , Resposta de Imobilidade Tônica/fisiologia , Masculino , Microinjeções , Inibição Neural/fisiologia , Vias Neurais/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Quinoxalinas/administração & dosagem , Quinoxalinas/farmacologia , Ratos , Ratos Transgênicos , Sacarose
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