A reusable benchmark of brain-age prediction from M/EEG resting-state signals.

Population-level modeling can define quantitative measures of individual aging by applying machine learning to large volumes of brain images. These measures of brain age, obtained from the general population, helped characterize disease severity in neurological populations, improving estimates of diagnosis or prognosis. Magnetoencephalography (MEG) and Electroencephalography (EEG) have the potential to further generalize this approach towards prevention and public health by enabling assessments of brain health at large scales in socioeconomically diverse environments. However, more research is needed to define methods that can handle the complexity and diversity of M/EEG signals across diverse real-world contexts. To catalyse this effort, here we propose reusable benchmarks of competing machine learning approaches for brain age modeling. We benchmarked popular classical machine learning pipelines and deep learning architectures previously used for pathology decoding or brain age estimation in 4 international M/EEG cohorts from diverse countries and cultural contexts, including recordings from more than 2500 participants. Our benchmarks were built on top of the M/EEG adaptations of the BIDS standard, providing tools that can be applied with minimal modification on any M/EEG dataset provided in the BIDS format. Our results suggest that, regardless of whether classical machine learning or deep learning was used, the highest performance was reached by pipelines and architectures involving spatially aware representations of the M/EEG signals, leading to R2 scores between 0.60-0.74. Hand-crafted features paired with random forest regression provided robust benchmarks even in situations in which other approaches failed. Taken together, this set of benchmarks, accompanied by open-source software and high-level Python scripts, can serve as a starting point and quantitative reference for future efforts at developing M/EEG-based measures of brain aging. The generality of the approach renders this benchmark reusable for other related objectives such as modeling specific cognitive variables or clinical endpoints.

Predictive regression modeling with MEG/EEG: from source power to signals and cognitive states.

Predicting biomedical outcomes from Magnetoencephalography and Electroencephalography (M/EEG) is central to applications like decoding, brain-computer-interfaces (BCI) or biomarker development and is facilitated by supervised machine learning. Yet, most of the literature is concerned with classification of outcomes defined at the event-level. Here, we focus on predicting continuous outcomes from M/EEG signal defined at the subject-level, and analyze about 600 MEG recordings from Cam-CAN dataset and about 1000 EEG recordings from TUH dataset. Considering different generative mechanisms for M/EEG signals and the biomedical outcome, we propose statistically-consistent predictive models that avoid source-reconstruction based on the covariance as representation. Our mathematical analysis and ground-truth simulations demonstrated that consistent function approximation can be obtained with supervised spatial filtering or by embedding with Riemannian geometry. Additional simulations revealed that Riemannian methods were more robust to model violations, in particular geometric distortions induced by individual anatomy. To estimate the relative contribution of brain dynamics and anatomy to prediction performance, we propose a novel model inspection procedure based on biophysical forward modeling. Applied to prediction of outcomes at the subject-level, the analysis revealed that the Riemannian model better exploited anatomical information while sensitivity to brain dynamics was similar across methods. We then probed the robustness of the models across different data cleaning options. Environmental denoising was globally important but Riemannian models were strikingly robust and continued performing well even without preprocessing. Our results suggest each method has its niche: supervised spatial filtering is practical for event-level prediction while the Riemannian model may enable simple end-to-end learning.

Repurposing electroencephalogram monitoring of general anaesthesia for building biomarkers of brain ageing: an exploratory study.

Background: Electroencephalography (EEG) is increasingly used for monitoring the depth of general anaesthesia, but EEG data from general anaesthesia monitoring are rarely reused for research. Here, we explored repurposing EEG monitoring from general anaesthesia for brain-age modelling using machine learning. We hypothesised that brain age estimated from EEG during general anaesthesia is associated with perioperative risk. Methods: We reanalysed four-electrode EEGs of 323 patients under stable propofol or sevoflurane anaesthesia to study four EEG signatures (95% of EEG power <8-13 Hz) for age prediction: total power, alpha-band power (8-13 Hz), power spectrum, and spatial patterns in frequency bands. We constructed age-prediction models from EEGs of a healthy reference group (ASA 1 or 2) during propofol anaesthesia. Although all signatures were informative, state-of-the-art age-prediction performance was unlocked by parsing spatial patterns across electrodes along the entire power spectrum (mean absolute error=8.2 yr; R2=0.65). Results: Clinical exploration in ASA 1 or 2 patients revealed that brain age was positively correlated with intraoperative burst suppression, a risk factor for general anaesthesia complications. Surprisingly, brain age was negatively correlated with burst suppression in patients with higher ASA scores, suggesting hidden confounders. Secondary analyses revealed that age-related EEG signatures were specific to propofol anaesthesia, reflected by limited model generalisation to anaesthesia maintained with sevoflurane. Conclusions: Although EEG from general anaesthesia may enable state-of-the-art age prediction, differences between anaesthetic drugs can impact the effectiveness and validity of brain-age models. To unleash the dormant potential of EEG monitoring for clinical research, larger datasets from heterogeneous populations with precisely documented drug dosage will be essential.

Combining magnetoencephalography with magnetic resonance imaging enhances learning of surrogate-biomarkers.

Electrophysiological methods, that is M/EEG, provide unique views into brain health. Yet, when building predictive models from brain data, it is often unclear how electrophysiology should be combined with other neuroimaging methods. Information can be redundant, useful common representations of multimodal data may not be obvious and multimodal data collection can be medically contraindicated, which reduces applicability. Here, we propose a multimodal model to robustly combine MEG, MRI and fMRI for prediction. We focus on age prediction as a surrogate biomarker in 674 subjects from the Cam-CAN dataset. Strikingly, MEG, fMRI and MRI showed additive effects supporting distinct brain-behavior associations. Moreover, the contribution of MEG was best explained by cortical power spectra between 8 and 30 Hz. Finally, we demonstrate that the model preserves benefits of stacking when some data is missing. The proposed framework, hence, enables multimodal learning for a wide range of biomarkers from diverse types of brain signals.

How old are you? What about your body, and your brain? People are used to answering this question by counting the years since birth. However, biological age could also be measured by looking at the integrity of the DNA in cells or by measuring the levels of proteins in the blood. Whether one goes by chronological age or biological age, each is simply an indicator of general health ­ but people with the same chronological age may have different biological ages, and vice versa. There are different imaging techniques that can be used to study the brain. A method called MRI reveals the brain's structure and the different types of tissue present, like white and grey matter. Functional MRIs (fMRIs for short) measure activity across different brain regions, while electrophysiology records electrical signals sent between neurons. Distinct features measured by all three techniques ­ MRI, fMRI and electrophysiology ­ have been associated with aging. For example, differences between younger and older people have been observed in the proportion of grey to white matter, the communication between certain brain regions, and the intensity of neural activity. MRIs, with their anatomical detail, remain the go-to for predicting the biological age of the brain. Patterns of neuronal activity captured by electrophysiology also provide information about how well the brain is working. However, it remains unclear how electrophysiology could be combined with other brain imaging methods, like MRI and fMRI. Can data from these three techniques be combined to better predict brain age? Engemann et al. designed a computer algorithm stacking electrophysiology data on top of MRI and fMRI imaging to assess the benefit of this three-pronged approach compared to using MRI alone. Brain scans from healthy people between 17 and 90 years old were used to build the computer model. The experiments showed that combining all three methods predicted brain age better. The predictions also correlated with the cognitive fitness of individuals. People whose brains were predicted to be older than their years tended to complain about the quality of their sleep and scored worse on memory and speed-thinking tasks. Crucially, Engemann et al. tested how the algorithm would hold up if some data were missing. This can happen in clinical practice where some tests are required but not others. Positively, prediction was maintained even with incomplete data, meaning this could be a useful clinical tool for characterizing the brain.

Propofol Requirement and EEG Alpha Band Power During General Anesthesia Provide Complementary Views on Preoperative Cognitive Decline.

Background: Although cognitive decline (CD) is associated with increased post-operative morbidity and mortality, routinely screening patients remains difficult. The main objective of this prospective study is to use the EEG response to a Propofol-based general anesthesia (GA) to reveal CD. Methods: 42 patients with collected EEG and Propofol target concentration infusion (TCI) during GA had a preoperative cognitive assessment using MoCA. We evaluated the performance of three variables to detect CD (MoCA < 25 points): age, Propofol requirement to induce unconsciousness (TCI at SEF95: 8-13 Hz) and the frontal alpha band power (AP at SEF95: 8-13 Hz). Results: The 17 patients (40%) with CD were significantly older (p < 0.001), had lower TCI (p < 0.001), and AP (p < 0.001). We found using logistic models that TCI and AP were the best set of variables associated with CD (AUC: 0.89) and performed better than age (p < 0.05). Propofol TCI had a greater impact on CD probability compared to AP, although both were complementary in detecting CD. Conclusion: TCI and AP contribute additively to reveal patient with preoperative cognitive decline. Further research on post-operative cognitive trajectory are necessary to confirm the interest of intra operative variables in addition or as a substitute to cognitive evaluation.

Corrected small-sample estimation of the Bayes error.

MOTIVATION: A major problem of pattern classification is estimation of the Bayes error when only small samples are available. One way to estimate the Bayes error is to design a classifier based on some classification rule applied to sample data, estimate the error of the designed classifier, and then use this estimate as an estimate of the Bayes error. Relative to the Bayes error, the expected error of the designed classifier is biased high, and this bias can be severe with small samples. RESULTS: This paper provides a correction for the bias by subtracting a term derived from the representation of the estimation error. It does so for Boolean classifiers, these being defined on binary features. Although the general theory applies to any Boolean classifier, a model is introduced to reduce the number of parameters. A key point is that the expected correction is conservative. Properties of the corrected estimate are studied via simulation. The correction applies to binary predictors because they are mathematically identical to Boolean classifiers. In this context the correction is adapted to the coefficient of determination, which has been used to measure nonlinear multivariate relations between genes and design genetic regulatory networks. An application using gene-expression data from a microarray experiment is provided on the website http://gspsnap.tamu.edu/smallsample/ (user:'smallsample', password:'smallsample)').