From sleep patterns to heart rhythm: Predicting atrial fibrillation from overnight polysomnograms.

BACKGROUND: Atrial fibrillation (AF) is often asymptomatic and thus under-observed. Given the high risks of stroke and heart failure among patients with AF, early prediction and effective management are crucial. Given the prevalence of obstructive sleep apnea among AF patients, electrocardiogram (ECG) analysis from polysomnography (PSG) offers a unique opportunity for early AF prediction. Our aim is to identify individuals at high risk of AF development from single­lead ECGs during standard PSG. METHODS: We analyzed 18,782 single­lead ECG recordings from 13,609 subjects undergoing PSG at the Massachusetts General Hospital sleep laboratory. AF presence was identified using ICD-9/10 codes. The dataset included 15,913 recordings without AF history and 2054 recordings from patients diagnosed with AF between one month to fifteen years post-PSG. Data were partitioned into training, validation, and test cohorts ensuring that individual patients remained exclusive to each cohort. The test set was held out during the training process. We employed two different methods for feature extraction to build a final model for AF prediction: Extraction of hand-crafted ECG features and a deep learning method. For extraction of ECG-hand-crafted features, recordings were split into 30-s windows, and those with a signal quality index (SQI) below 0.95 were discarded. From each remaining window, 150 features were extracted from the time, frequency, time-frequency domains, and phase-space reconstructions of the ECG. A compilation of 12 statistical features summarized these window-specific features per recording, resulting in 1800 features (12 × 150). A pre-trained deep neural network from the PhysioNet Challenge 2021 was updated using transfer learning to discriminate recordings with and without AF. The model processed PSG ECGs in 16-s windows to generate AF probabilities, from which 13 statistical features were extracted. Combining 1800 features from feature extraction with 13 from the deep learning model, we performed a feature selection and subsequently trained a shallow neural network to predict future AF and evaluated its performance on the test cohort. RESULTS: On the test set, our model exhibited sensitivity, specificity, and precision of 0.67, 0.81, and 0.3, respectively, for AF prediction. Survival analysis revealed a hazard ratio of 8.36 (p-value: 1.93 × 10-52) for AF outcomes using the log-rank test. CONCLUSIONS: Our proposed ECG analysis method, utilizing overnight PSG data, shows promise in AF prediction despite modest precision, suggesting false positives. This approach could enable low-cost screening and proactive treatment for high-risk patients. Refinements, including additional physiological parameters, may reduce false positives, enhancing clinical utility and accuracy.

High prevalence of sleep-disordered breathing in the intensive care unit - a cross-sectional study.

PURPOSE: Sleep-disordered breathing may be induced by, exacerbate, or complicate recovery from critical illness. Disordered breathing during sleep, which itself is often fragmented, can go unrecognized in the intensive care unit (ICU). The objective of this study was to investigate the prevalence, severity, and risk factors of sleep-disordered breathing in ICU patients using a single respiratory belt and oxygen saturation signals. METHODS: Patients in three ICUs at Massachusetts General Hospital wore a thoracic respiratory effort belt as part of a clinical trial for up to 7 days and nights. Using a previously developed machine learning algorithm, we processed respiratory and oximetry signals to measure the 3% apnea-hypopnea index (AHI) and estimate AH-specific hypoxic burden and periodic breathing. We trained models to predict AHI categories for 12-h segments from risk factors, including admission variables and bio-signals data, available at the start of these segments. RESULTS: Of 129 patients, 68% had an AHI ≥ 5; 40% an AHI > 15, and 19% had an AHI > 30 while critically ill. Median [interquartile range] hypoxic burden was 2.8 [0.5, 9.8] at night and 4.2 [1.0, 13.7] %min/h during the day. Of patients with AHI ≥ 5, 26% had periodic breathing. Performance of predicting AHI-categories from risk factors was poor. CONCLUSIONS: Sleep-disordered breathing and sleep apnea events while in the ICU are common and are associated with substantial burden of hypoxia and periodic breathing. Detection is feasible using limited bio-signals, such as respiratory effort and SpO2 signals, while risk factors were insufficient to predict AHI severity.

Classification of neurologic outcomes from medical notes using natural language processing.

Neurologic disability level at hospital discharge is an important outcome in many clinical research studies. Outside of clinical trials, neurologic outcomes must typically be extracted by labor intensive manual review of clinical notes in the electronic health record (EHR). To overcome this challenge, we set out to develop a natural language processing (NLP) approach that automatically reads clinical notes to determine neurologic outcomes, to make it possible to conduct larger scale neurologic outcomes studies. We obtained 7314 notes from 3632 patients hospitalized at two large Boston hospitals between January 2012 and June 2020, including discharge summaries (3485), occupational therapy (1472) and physical therapy (2357) notes. Fourteen clinical experts reviewed notes to assign scores on the Glasgow Outcome Scale (GOS) with 4 classes, namely 'good recovery', 'moderate disability', 'severe disability', and 'death' and on the Modified Rankin Scale (mRS), with 7 classes, namely 'no symptoms', 'no significant disability', 'slight disability', 'moderate disability', 'moderately severe disability', 'severe disability', and 'death'. For 428 patients' notes, 2 experts scored the cases generating interrater reliability estimates for GOS and mRS. After preprocessing and extracting features from the notes, we trained a multiclass logistic regression model using LASSO regularization and 5-fold cross validation for hyperparameter tuning. The model performed well on the test set, achieving a micro average area under the receiver operating characteristic and F-score of 0.94 (95% CI 0.93-0.95) and 0.77 (0.75-0.80) for GOS, and 0.90 (0.89-0.91) and 0.59 (0.57-0.62) for mRS, respectively. Our work demonstrates that an NLP algorithm can accurately assign neurologic outcomes based on free text clinical notes. This algorithm increases the scale of research on neurological outcomes that is possible with EHR data.

Physiological Assessment of Delirium Severity: The Electroencephalographic Confusion Assessment Method Severity Score (E-CAM-S).

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.

Automated Annotation of Epileptiform Burden and Its Association with Outcomes.

OBJECTIVE: This study was undertaken to determine the dose-response relation between epileptiform activity burden and outcomes in acutely ill patients. METHODS: A single center retrospective analysis was made of 1,967 neurologic, medical, and surgical patients who underwent >16 hours of continuous electroencephalography (EEG) between 2011 and 2017. We developed an artificial intelligence algorithm to annotate 11.02 terabytes of EEG and quantify epileptiform activity burden within 72 hours of recording. We evaluated burden (1) in the first 24 hours of recording, (2) in the 12-hours epoch with highest burden (peak burden), and (3) cumulatively through the first 72 hours of monitoring. Machine learning was applied to estimate the effect of epileptiform burden on outcome. Outcome measure was discharge modified Rankin Scale, dichotomized as good (0-4) versus poor (5-6). RESULTS: Peak epileptiform burden was independently associated with poor outcomes (p < 0.0001). Other independent associations included age, Acute Physiology and Chronic Health Evaluation II score, seizure on presentation, and diagnosis of hypoxic-ischemic encephalopathy. Model calibration error was calculated across 3 strata based on the time interval between last EEG measurement (up to 72 hours of monitoring) and discharge: (1) <5 days between last measurement and discharge, 0.0941 (95% confidence interval [CI] = 0.0706-0.1191); 5 to 10 days between last measurement and discharge, 0.0946 (95% CI = 0.0631-0.1290); >10 days between last measurement and discharge, 0.0998 (95% CI = 0.0698-0.1335). After adjusting for covariates, increase in peak epileptiform activity burden from 0 to 100% increased the probability of poor outcome by 35%. INTERPRETATION: Automated measurement of peak epileptiform activity burden affords a convenient, consistent, and quantifiable target for future multicenter randomized trials investigating whether suppressing epileptiform activity improves outcomes. ANN NEUROL 2021;90:300-311.

Sleep apnea and respiratory anomaly detection from a wearable band and oxygen saturation.

OBJECTIVE: Sleep-related respiratory abnormalities are typically detected using polysomnography. There is a need in general medicine and critical care for a more convenient method to detect sleep apnea automatically from a simple, easy-to-wear device. The objective was to detect abnormal respiration and estimate the Apnea-Hypopnea Index (AHI) automatically with a wearable respiratory device with and without SpO2 signals using a large (n = 412) dataset serving as ground truth. DESIGN: Simultaneously recorded polysomnography (PSG) and wearable respiratory effort data were used to train and evaluate models in a cross-validation fashion. Time domain and complexity features were extracted, important features were identified, and a random forest model was employed to detect events and predict AHI. Four models were trained: one each using the respiratory features only, a feature from the SpO2 (%)-signal only, and two additional models that use the respiratory features and the SpO2 (%) feature, one allowing a time lag of 30 s between the two signals. RESULTS: Event-based classification resulted in areas under the receiver operating characteristic curves of 0.94, 0.86, and 0.82, and areas under the precision-recall curves of 0.48, 0.32, and 0.51 for the models using respiration and SpO2, respiration-only, and SpO2-only, respectively. Correlation between expert-labelled and predicted AHI was 0.96, 0.78, and 0.93, respectively. CONCLUSIONS: A wearable respiratory effort signal with or without SpO2 signal predicted AHI accurately, and best performance was achieved with using both signals.

CoVA: An Acuity Score for Outpatient Screening that Predicts Coronavirus Disease 2019 Prognosis.

BACKGROUND: We sought to develop an automatable score to predict hospitalization, critical illness, or death for patients at risk for coronavirus disease 2019 (COVID-19) presenting for urgent care. METHODS: We developed the COVID-19 Acuity Score (CoVA) based on a single-center study of adult outpatients seen in respiratory illness clinics or the emergency department. Data were extracted from the Partners Enterprise Data Warehouse, and split into development (n = 9381, 7 March-2 May) and prospective (n = 2205, 3-14 May) cohorts. Outcomes were hospitalization, critical illness (intensive care unit or ventilation), or death within 7 days. Calibration was assessed using the expected-to-observed event ratio (E/O). Discrimination was assessed by area under the receiver operating curve (AUC). RESULTS: In the prospective cohort, 26.1%, 6.3%, and 0.5% of patients experienced hospitalization, critical illness, or death, respectively. CoVA showed excellent performance in prospective validation for hospitalization (expected-to-observed ratio [E/O]: 1.01; AUC: 0.76), for critical illness (E/O: 1.03; AUC: 0.79), and for death (E/O: 1.63; AUC: 0.93). Among 30 predictors, the top 5 were age, diastolic blood pressure, blood oxygen saturation, COVID-19 testing status, and respiratory rate. CONCLUSIONS: CoVA is a prospectively validated automatable score for the outpatient setting to predict adverse events related to COVID-19 infection.

Development and Validation of Forecasting Next Reported Seizure Using e-Diaries.

OBJECTIVE: There are no validated methods for predicting the timing of seizures. Using machine learning, we sought to forecast 24-hour risk of self-reported seizure from e-diaries. METHODS: Data from 5,419 patients on SeizureTracker.com (including seizure count, type, and duration) were split into training (3,806 patients/1,665,215 patient-days) and testing (1,613 patients/549,588 patient-days) sets with no overlapping patients. An artificial intelligence (AI) program, consisting of recurrent networks followed by a multilayer perceptron ("deep learning" model), was trained to produce risk forecasts. Forecasts were made from a sliding window of 3-month diary history for each day of each patient's diary. After training, the model parameters were held constant and the testing set was scored. A rate-matched random (RMR) forecast was compared to the AI. Comparisons were made using the area under the receiver operating characteristic curve (AUC), a measure of binary discrimination performance, and the Brier score, a measure of forecast calibration. The Brier skill score (BSS) measured the improvement of the AI Brier score compared to the benchmark RMR Brier score. Confidence intervals (CIs) on performance statistics were obtained via bootstrapping. RESULTS: The AUC was 0.86 (95% CI = 0.85-0.88) for AI and 0.83 (95% CI = 0.81-0.85) for RMR, favoring AI (p < 0.001). Overall (all patients combined), BSS was 0.27 (95% CI = 0.23-0.31), also favoring AI (p < 0.001). INTERPRETATION: The AI produced a valid forecast superior to a chance forecaster, and provided meaningful forecasts in the majority of patients. Future studies will be needed to quantify the clinical value of these forecasts for patients. ANN NEUROL 2020;88:588-595.

Postoperative delirium mediates 180-day mortality in orthopaedic trauma patients.

BACKGROUND: Frailty has been associated with increased incidence of postoperative delirium and mortality. We hypothesised that postoperative delirium mediates a clinically significant (≥1%) percentage of the effect of frailty on mortality in older orthopaedic trauma patients. METHODS: This was a single-centre, retrospective observational study including 558 adults 65 yr and older, who presented with an extremity fracture requiring hospitalisation without initial ICU admission. We used causal statistical inference methods to estimate the relationships between frailty, postoperative delirium, and mortality. RESULTS: In the cohort, 180-day mortality rate was 6.5% (36/558). Frail and prefrail patients comprised 23% and 39%, respectively, of the study cohort. Frailty was associated with increased 180 day mortality from 1.4% to 12.2% (11% difference; 95% confidence interval [CI], 8.4-13.6), which translated statistically into an 88.7% (79.9-94.3%) direct effect and an 11.3% (5.7-20.1%) postoperative delirium mediated effect. Prefrailty was also associated with increased 180 day mortality from 1.4% to 4.4% (2.9% difference; 2.4-3.4), which was translated into a 92.5% (83.8-99.9%) direct effect and a 7.5% (0.1-16.2%) postoperative delirium mediated effect. CONCLUSIONS: Frailty is associated with increased postoperative mortality, and delirium might mediate a clinically significant, but small percentage of this effect. Studies should assess whether, in patients with frailty, attempts to mitigate delirium might decrease postoperative mortality.

Burden of Epileptiform Activity Predicts Discharge Neurologic Outcomes in Severe Acute Ischemic Stroke.

BACKGROUND/OBJECTIVES: Clinical seizures following acute ischemic stroke (AIS) appear to contribute to worse neurologic outcomes. However, the effect of electrographic epileptiform abnormalities (EAs) more broadly is less clear. Here, we evaluate the impact of EAs, including electrographic seizures and periodic and rhythmic patterns, on outcomes in patients with AIS. METHODS: This is a retrospective study of all patients with AIS aged ≥ 18 years who underwent at least 18 h of continuous electroencephalogram (EEG) monitoring at a single center between 2012 and 2017. EAs were classified according to American Clinical Neurophysiology Society (ACNS) nomenclature and included seizures and periodic and rhythmic patterns. EA burden for each 24-h epoch was defined using the following cutoffs: EA presence, maximum daily burden < 10% versus > 10%, maximum daily burden < 50% versus > 50%, and maximum daily burden using categories from ACNS nomenclature ("rare" < 1%; "occasional" 1-9%; "frequent" 10-49%; "abundant" 50-89%; "continuous" > 90%). Maximum EA frequency for each epoch was dichotomized into ≥ 1.5 Hz versus < 1.5 Hz. Poor neurologic outcome was defined as a modified Rankin Scale score of 4-6 (vs. 0-3 as good outcome) at hospital discharge. RESULTS: One hundred and forty-three patients met study inclusion criteria. Sixty-seven patients (46.9%) had EAs. One hundred and twenty-four patients (86.7%) had poor outcome. On univariate analysis, the presence of EAs (OR 3.87 [1.27-11.71], p = 0.024) and maximum daily burden > 10% (OR 12.34 [2.34-210], p = 0.001) and > 50% (OR 8.26 [1.34-122], p = 0.035) were associated with worse outcomes. On multivariate analysis, after adjusting for clinical covariates (age, gender, NIHSS, APACHE II, stroke location, stroke treatment, hemorrhagic transformation, Charlson comorbidity index, history of epilepsy), EA presence (OR 5.78 [1.36-24.56], p = 0.017), maximum daily burden > 10% (OR 23.69 [2.43-230.7], p = 0.006), and maximum daily burden > 50% (OR 9.34 [1.01-86.72], p = 0.049) were associated with worse outcomes. After adjusting for covariates, we also found a dose-dependent association between increasing EA burden and increasing probability of poor outcomes (OR 1.89 [1.18-3.03] p = 0.009). We did not find an independent association between EA frequency and outcomes (OR: 4.43 [.98-20.03] p = 0.053). However, the combined effect of increasing EA burden and frequency ≥ 1.5 Hz (EA burden * frequency) was significantly associated with worse outcomes (OR 1.64 [1.03-2.63] p = 0.039). CONCLUSIONS: Electrographic seizures and periodic and rhythmic patterns in patients with AIS are associated with worse outcomes in a dose-dependent manner. Future studies are needed to assess whether treatment of this EEG activity can improve outcomes.

Burst Suppression: Causes and Effects on Mortality in Critical Illness.

BACKGROUND: Burst suppression in mechanically ventilated intensive care unit (ICU) patients is associated with increased mortality. However, the relative contributions of propofol use and critical illness itself to burst suppression; of burst suppression, propofol, and critical illness to mortality; and whether preventing burst suppression might reduce mortality, have not been quantified. METHODS: The dataset contains 471 adults from seven ICUs, after excluding anoxic encephalopathy due to cardiac arrest or intentional burst suppression for therapeutic reasons. We used multiple prediction and causal inference methods to estimate the effects connecting burst suppression, propofol, critical illness, and in-hospital mortality in an observational retrospective study. We also estimated the effects mediated by burst suppression. Sensitivity analysis was used to assess for unmeasured confounding. RESULTS: The expected outcomes in a "counterfactual" randomized controlled trial (cRCT) that assigned patients to mild versus severe illness are expected to show a difference in burst suppression burden of 39%, 95% CI [8-66]%, and in mortality of 35% [29-41]%. Assigning patients to maximal (100%) burst suppression burden is expected to increase mortality by 12% [7-17]% compared to 0% burden. Burst suppression mediates 10% [2-21]% of the effect of critical illness on mortality. A high cumulative propofol dose (1316 mg/kg) is expected to increase burst suppression burden by 6% [0.8-12]% compared to a low dose (284 mg/kg). Propofol exposure has no significant direct effect on mortality; its effect is entirely mediated through burst suppression. CONCLUSIONS: Our analysis clarifies how important factors contribute to mortality in ICU patients. Burst suppression appears to contribute to mortality but is primarily an effect of critical illness rather than iatrogenic use of propofol.

Learning Polychronous Neuronal Groups Using Joint Weight-Delay Spike-Timing-Dependent Plasticity.

Polychronous neuronal group (PNG), a type of cell assembly, is one of the putative mechanisms for neural information representation. According to the reader-centric definition, some readout neurons can become selective to the information represented by polychronous neuronal groups under ongoing activity. Here, in computational models, we show that the frequently activated polychronous neuronal groups can be learned by readout neurons with joint weight-delay spike-timing-dependent plasticity. The identity of neurons in the group and their expected spike timing at millisecond scale can be recovered from the incoming weights and delays of the readout neurons. The detection performance can be further improved by two layers of readout neurons. In this way, the detection of polychronous neuronal groups becomes an intrinsic part of the network, and the readout neurons become differentiated members in the group to indicate whether subsets of the group have been activated according to their spike timing. The readout spikes representing this information can be used to analyze how PNGs interact with each other or propagate to downstream networks for higher-level processing.

iPEAP: integrating multiple omics and genetic data for pathway enrichment analysis.

UNLABELLED: A challenge in biodata analysis is to understand the underlying phenomena among many interactions in signaling pathways. Such study is formulated as the pathway enrichment analysis, which identifies relevant pathways functional enriched in high-throughput data. The question faced here is how to analyze different data types in a unified and integrative way by characterizing pathways that these data simultaneously reveal. To this end, we developed integrative Pathway Enrichment Analysis Platform, iPEAP, which handles transcriptomics, proteomics, metabolomics and GWAS data under a unified aggregation schema. iPEAP emphasizes on the ability to aggregate various pathway enrichment results generated in different high-throughput experiments, as well as the quantitative measurements of different ranking results, thus providing the first benchmark platform for integration, comparison and evaluation of multiple types of data and enrichment methods. AVAILABILITY AND IMPLEMENTATION: iPEAP is freely available at http://www.tongji.edu.cn/∼qiliu/ipeap.html.

Refining sleep staging accuracy: Transfer learning coupled with scorability models.

STUDY OBJECTIVES: This study aimed to 1) improve sleep staging accuracy through transfer learning, to achieve or exceede human inter-expert agreement; 2) introduce a scorability model to assess the quality and trustworthiness of automated sleep staging. METHODS: A deep neural network (base model) was trained on a large multi-site polysomnography (PSG) dataset from the United States. Transfer learning was used to calibrate the model to a reduced montage and limited samples from the Korean Genome and Epidemiology Study (KoGES) dataset. Model performance was compared to inter-expert reliability among three human experts. A scorability assessment was developed to predict the agreement between the model and human experts. RESULTS: Initial sleep staging by the base model showed lower agreement with experts (κ=0.55) compared to inter-expert agreement (κ=0.62). Calibration with 324 randomly sampled training cases matched expert agreement levels. Further targeted sampling improved performance, with models exceeding inter-expert agreement (κ=0.70). The scorability assessment, combining biosignal quality and model confidence features, predicted model-expert agreement moderately well (R²=0.42). Recordings with higher scorability scores demonstrated greater model-expert agreement than inter-expert agreement. Even with lower scorability scores, model performance was comparable to inter-expert agreement. CONCLUSIONS: Fine-tuning a pre-trained neural network through targeted transfer learning significantly enhances sleep staging performance for an atypical montage, achieving and surpassing human expert agreement levels. The introduction of a scorability assessment provides a robust measure of reliability, ensuring quality control and enhancing the practical application of the system before deployment. This approach marks an important advancement in automated sleep analysis, demonstrating the potential for AI to exceed human performance in clinical settings.

What Radio Waves Tell Us about Sleep!

The ability to assess sleep at home, capture sleep stages, and detect the occurrence of apnea (without on-body sensors) simply by analyzing the radio waves bouncing off people's bodies while they sleep is quite powerful. Such a capability would allow for longitudinal data collection in patients' homes, informing our understanding of sleep and its interaction with various diseases and their therapeutic responses, both in clinical trials and routine care. In this article, we develop an advanced machine learning algorithm for passively monitoring sleep and nocturnal breathing from radio waves reflected off people while asleep. Validation results in comparison with the gold standard (i.e., polysomnography) (n=880) demonstrate that the model captures the sleep hypnogram (with an accuracy of 80.5% for 30-second epochs categorized into Wake, Light Sleep, Deep Sleep, or REM), detects sleep apnea (AUROC = 0.89), and measures the patient's Apnea-Hypopnea Index (ICC=0.90; 95% CI = [0.88, 0.91]). Notably, the model exhibits equitable performance across race, sex, and age. Moreover, the model uncovers informative interactions between sleep stages and a range of diseases including neurological, psychiatric, cardiovascular, and immunological disorders. These findings not only hold promise for clinical practice and interventional trials but also underscore the significance of sleep as a fundamental component in understanding and managing various diseases.

How many patients do you need? Investigating trial designs for anti-seizure treatment in acute brain injury patients.

BACKGROUND/OBJECTIVES: Epileptiform activity (EA), including seizures and periodic patterns, worsens outcomes in patients with acute brain injuries (e.g., aneurysmal subarachnoid hemorrhage [aSAH]). Randomized control trials (RCTs) assessing anti-seizure interventions are needed. Due to scant drug efficacy data and ethical reservations with placebo utilization, and complex physiology of acute brain injury, RCTs are lacking or hindered by design constraints. We used a pharmacological model-guided simulator to design and determine the feasibility of RCTs evaluating EA treatment. METHODS: In a single-center cohort of adults (age >18) with aSAH and EA, we employed a mechanistic pharmacokinetic-pharmacodynamic framework to model treatment response using observational data. We subsequently simulated RCTs for levetiracetam and propofol, each with three treatment arms mirroring clinical practice and an additional placebo arm. Using our framework, we simulated EA trajectories across treatment arms. We predicted discharge modified Rankin Scale as a function of baseline covariates, EA burden, and drug doses using a double machine learning model learned from observational data. Differences in outcomes across arms were used to estimate the required sample size. RESULTS: Sample sizes ranged from 500 for levetiracetam 7 mg/kg versus placebo, to >4000 for levetiracetam 15 versus 7 mg/kg to achieve 80% power (5% type I error). For propofol 1 mg/kg/h versus placebo, 1200 participants were needed. Simulations comparing propofol at varying doses did not reach 80% power even at samples >1200. CONCLUSIONS: Our simulations using drug efficacy show sample sizes are infeasible, even for potentially unethical placebo-control trials. We highlight the strength of simulations with observational data to inform the null hypotheses and propose use of this simulation-based RCT paradigm to assess the feasibility of future trials of anti-seizure treatment in acute brain injury.

Altered Motor Activity Patterns within 10-Minute Timescale Predict Incident Clinical Alzheimer's Disease.

Background: Fractal motor activity regulation (FMAR), characterized by self-similar temporal patterns in motor activity across timescales, is robust in healthy young humans but degrades with aging and in Alzheimer's disease (AD). Objective: To determine the timescales where alterations of FMAR can best predict the clinical onset of AD. Methods: FMAR was assessed from actigraphy at baseline in 1,077 participants who had annual follow-up clinical assessments for up to 15 years. Survival analysis combined with deep learning (DeepSurv) was used to examine how baseline FMAR at different timescales from 3 minutes up to 6 hours contributed differently to the risk for incident clinical AD. Results: Clinical AD occurred in 270 participants during the follow-up. DeepSurv identified three potential regions of timescales in which FMAR alterations were significantly linked to the risk for clinical AD: <10, 20-40, and 100-200 minutes. Confirmed by the Cox and random survival forest models, the effect of FMAR alterations in the timescale of <10 minutes was the strongest, after adjusting for covariates. Conclusions: Subtle changes in motor activity fluctuations predicted the clinical onset of AD, with the strongest association observed in activity fluctuations at timescales <10 minutes. These findings suggest that short actigraphy recordings may be used to assess the risk of AD.

Classification of autism spectrum disorder using electroencephalography in Chinese children: a cross-sectional retrospective study.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by diverse clinical features. EEG biomarkers such as spectral power and functional connectivity have emerged as potential tools for enhancing early diagnosis and understanding of the neural processes underlying ASD. However, existing studies yield conflicting results, necessitating a comprehensive, data-driven analysis. We conducted a retrospective cross-sectional study involving 246 children with ASD and 42 control children. EEG was collected, and diverse EEG features, including spectral power and spectral coherence were extracted. Statistical inference methods, coupled with machine learning models, were employed to identify differences in EEG features between ASD and control groups and develop classification models for diagnostic purposes. Our analysis revealed statistically significant differences in spectral coherence, particularly in gamma and beta frequency bands, indicating elevated long range functional connectivity between frontal and parietal regions in the ASD group. Machine learning models achieved modest classification performance of ROC-AUC at 0.65. While machine learning approaches offer some discriminative power classifying individuals with ASD from controls, they also indicate the need for further refinement.

Linking brain structure, cognition, and sleep: insights from clinical data.

STUDY OBJECTIVES: To use relatively noisy routinely collected clinical data (brain magnetic resonance imaging (MRI) data, clinical polysomnography (PSG) recordings, and neuropsychological testing), to investigate hypothesis-driven and data-driven relationships between brain physiology, structure, and cognition. METHODS: We analyzed data from patients with clinical PSG, brain MRI, and neuropsychological evaluations. SynthSeg, a neural network-based tool, provided high-quality segmentations despite noise. A priori hypotheses explored associations between brain function (measured by PSG) and brain structure (measured by MRI). Associations with cognitive scores and dementia status were studied. An exploratory data-driven approach investigated age-structure-physiology-cognition links. RESULTS: Six hundred and twenty-three patients with sleep PSG and brain MRI data were included in this study; 160 with cognitive evaluations. Three hundred and forty-two participants (55%) were female, and age interquartile range was 52 to 69 years. Thirty-six individuals were diagnosed with dementia, 71 with mild cognitive impairment, and 326 with major depression. One hundred and fifteen individuals were evaluated for insomnia and 138 participants had an apnea-hypopnea index equal to or greater than 15. Total PSG delta power correlated positively with frontal lobe/thalamic volumes, and sleep spindle density with thalamic volume. rapid eye movement (REM) duration and amygdala volume were positively associated with cognition. Patients with dementia showed significant differences in five brain structure volumes. REM duration, spindle, and slow-oscillation features had strong associations with cognition and brain structure volumes. PSG and MRI features in combination predicted chronological age (R2 = 0.67) and cognition (R2 = 0.40). CONCLUSIONS: Routine clinical data holds extended value in understanding and even clinically using brain-sleep-cognition relationships.