Unsupervised multimodal modeling of cognitive and brain health trajectories for early dementia prediction.

Predicting the course of neurodegenerative disorders early has potential to greatly improve clinical management and patient outcomes. A key challenge for early prediction in real-world clinical settings is the lack of labeled data (i.e., clinical diagnosis). In contrast to supervised classification approaches that require labeled data, we propose an unsupervised multimodal trajectory modeling (MTM) approach based on a mixture of state space models that captures changes in longitudinal data (i.e., trajectories) and stratifies individuals without using clinical diagnosis for model training. MTM learns the relationship between states comprising expensive, invasive biomarkers (ß-amyloid, grey matter density) and readily obtainable cognitive observations. MTM training on trajectories stratifies individuals into clinically meaningful clusters more reliably than MTM training on baseline data alone and is robust to missing data (i.e., cognitive data alone or single assessments). Extracting an individualized cognitive health index (i.e., MTM-derived cluster membership index) allows us to predict progression to AD more precisely than standard clinical assessments (i.e., cognitive tests or MRI scans alone). Importantly, MTM generalizes successfully from research cohort to real-world clinical data from memory clinic patients with missing data, enhancing the clinical utility of our approach. Thus, our multimodal trajectory modeling approach provides a cost-effective and non-invasive tool for early dementia prediction without labeled data (i.e., clinical diagnosis) with strong potential for translation to clinical practice.

Modified MRI Anonymization (De-Facing) for Improved MEG Coregistration.

Localising the sources of MEG/EEG signals often requires a structural MRI to create a head model, while ensuring reproducible scientific results requires sharing data and code. However, sharing structural MRI data often requires the face go be hidden to help protect the identity of the individuals concerned. While automated de-facing methods exist, they tend to remove the whole face, which can impair methods for coregistering the MRI data with the EEG/MEG data. We show that a new, automated de-facing method that retains the nose maintains good MRI-MEG/EEG coregistration. Importantly, behavioural data show that this "face-trimming" method does not increase levels of identification relative to a standard de-facing approach and has less effect on the automated segmentation and surface extraction sometimes used to create head models for MEG/EEG localisation. We suggest that this trimming approach could be employed for future sharing of structural MRI data, at least for those to be used in forward modelling (source reconstruction) of EEG/MEG data.

A multi-site, multi-participant magnetoencephalography resting-state dataset to study dementia: The BioFIND dataset.

Early detection of Alzheimer's Disease (AD) is vital to reduce the burden of dementia and for developing effective treatments. Neuroimaging can detect early brain changes, such as hippocampal atrophy in Mild Cognitive Impairment (MCI), a prodromal state of AD. However, selecting the most informative imaging features by machine-learning requires many cases. While large publically-available datasets of people with dementia or prodromal disease exist for Magnetic Resonance Imaging (MRI), comparable datasets are missing for Magnetoencephalography (MEG). MEG offers advantages in its millisecond resolution, revealing physiological changes in brain oscillations or connectivity before structural changes are evident with MRI. We introduce a MEG dataset with 324 individuals: patients with MCI and healthy controls. Their brain activity was recorded while resting with eyes closed, using a 306-channel MEG scanner at one of two sites (Madrid or Cambridge), enabling tests of generalization across sites. A T1-weighted MRI is provided to assist source localisation. The MEG and MRI data are formatted according to international BIDS standards and analysed freely on the DPUK platform (https://portal.dementiasplatform.uk/Apply). Here, we describe this dataset in detail, report some example (benchmark) analyses, and consider its limitations and future directions.

Late combination shows that MEG adds to MRI in classifying MCI versus controls.

Early detection of Alzheimer's disease (AD) is essential for developing effective treatments. Neuroimaging techniques like Magnetic Resonance Imaging (MRI) have the potential to detect brain changes before symptoms emerge. Structural MRI can detect atrophy related to AD, but it is possible that functional changes are observed even earlier. We therefore examined the potential of Magnetoencephalography (MEG) to detect differences in functional brain activity in people with Mild Cognitive Impairment (MCI) - a state at risk of early AD. We introduce a framework for multimodal combination to ask whether MEG data from a resting-state provides complementary information beyond structural MRI data in the classification of MCI versus controls. More specifically, we used multi-kernel learning of support vector machines to classify 163 MCI cases versus 144 healthy elderly controls from the BioFIND dataset. When using the covariance of planar gradiometer data in the low Gamma range (30-48 Hz), we found that adding a MEG kernel improved classification accuracy above kernels that captured several potential confounds (e.g., age, education, time-of-day, head motion). However, accuracy using MEG alone (68%) was worse than MRI alone (71%). When simply concatenating (normalized) features from MEG and MRI into one kernel (Early combination), there was no advantage of combining MEG with MRI versus MRI alone. When combining kernels of modality-specific features (Intermediate combination), there was an improvement in multimodal classification to 74%. The biggest multimodal improvement however occurred when we combined kernels from the predictions of modality-specific classifiers (Late combination), which achieved 77% accuracy (a reliable improvement in terms of permutation testing). We also explored other MEG features, such as the variance versus covariance of magnetometer versus planar gradiometer data within each of 6 frequency bands (delta, theta, alpha, beta, low gamma, or high gamma), and found that they generally provided complementary information for classification above MRI. We conclude that MEG can improve on the MRI-based classification of MCI.