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

Aging is associated with structural brain changes, cognitive decline, and neurodegenerative diseases. Brain age, an imaging biomarker sensitive to deviations from healthy aging, offers insights into structural aging variations and is a potential prognostic biomarker in neurodegenerative conditions. This study introduces BrainAgeNeXt, a novel convolutional neural network inspired by the MedNeXt framework, designed to predict brain age from T1-weighted magnetic resonance imaging (MRI) scans. BrainAgeNeXt was trained and validated on 11,574 MRI scans from 33 private and publicly available datasets of healthy volunteers, aged 5 to 95 years, imaged with 3T and 7T MRI. Performance was compared against three state-of-the-art brain age prediction methods. BrainAgeNeXt achieved a mean absolute error (MAE) of 2.78 years, lower than the compared methods (MAE = 3.55, 3.59, and 4.16 years, respectively). We tested all methods also across different levels of image quality, and BrainAgeNeXt performed well even with motion artifacts and less common 7T MRI data. In three longitudinal multiple sclerosis (MS) cohorts (273 individuals), brain age was, on average, 4.21 years greater than chronological age. Longitudinal analysis indicated that brain age increased by 1.15 years per chronological year in individuals with MS (95% CI = [1.05, 1.26]). Moreover, in early MS, individuals with worsening disability had a higher annual increase in brain age compared to those with stable clinical assessments (1.24 vs. 0.75, p < 0.01). These findings suggest that brain age is a promising prognostic biomarker for MS progression and potentially a valuable endpoint for clinical trials.

BrainAgeNeXt: Advancing Brain Age Modeling for Individuals with Multiple Sclerosis

Electroencephalography (EEG) has a long history as a clinical tool to study brain function, and its potential to derive biomarkers for various applications is far from exhausted. Machine learning (ML) can guide future innovation by harnessing the wealth of complex EEG signals to isolate relevant brain activity. Yet, ML studies in EEG tend to ignore physiological artifacts, which may cause problems for deriving biomarkers specific to the central nervous system (CNS). We present a framework for conceptualizing machine learning from CNS versus peripheral signals measured with EEG. A common signal representation across the frequency spectrum based on Morlet wavelets allowed us to define traditional brain activity features (e.g. log power) and alternative inputs used by state-of-the-art ML approaches (covariance matrices). Using more than 2600 EEG recordings from large public databases (TUAB, TDBRAIN), we studied the impact of peripheral signals and artifact removal techniques on ML models in exemplary age- and sex-prediction analyses. Across benchmarks, basic artifact rejection improved model performance whereas further removal of peripheral signals using ICA decreased performance. Our analyses revealed that peripheral signals enable age and sex prediction. However, they explained only a fraction of the performance provided by brain signals. We show that brain signals and body signals, both reflected in the EEG, allow for prediction of personal characteristics. While these results may depend on specific prediction problems, our work suggests that great care is needed to separate these signals when the goal is to develop CNS-specific biomarkers using ML.

Machine learning of brain-specific biomarkers from EEG

[Background] Data from neuro-imaging techniques allow us to estimate a brain9s age. Brain age is easily interpretable as "how old the brain looks", and could therefore be an attractive communication tool for brain health in clinical practice. This study aimed to investigate its clinical utility.
[Objectives] To investigate the relationship between brain age and information processing speed in MS.
[Methods] A ridge-regression model was trained to predict age from brain MRI volumetric features and sex in a healthy control dataset (HC_train, n=1690). This model was used to predict brain age in two test sets: HC_test (n=50) and MS_test (n=201). Brain-Predicted Age Difference (BPAD) was calculated as BPAD=brain age minus chronological age. Information processing speed was assessed with the Symbol Digit Modalities Test (SDMT).
[Results] Brain age was significantly related to SDMT scores in the MS_test dataset (r=-0.44, p<.001), and contributed uniquely to variance in SDMT beyond chronological age, reflected by a significant correlation between BPAD and SDMT (r=-0.21, p=0.003) and a significant weight (-0.21, p=0.011) in a multivariate regression equation with age.
[Conclusions] Brain age is a candidate biomarker for information processing speed in MS and an easy to grasp metric for brain health.

/pdf/brain-age-as-a-surrogate-marker-for-information-processing-504lcj2pd7.pdf

Brain age as a surrogate marker for information processing speed in multiple sclerosis

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Brain age as a surrogate marker for information processing speed in multiple sclerosis