Biology subjects

Woolrich, M.

Publications and source records attributed to Woolrich, M..

16 recordsLinked to original sources

bioRxiv2026

Neural Fingerprinting based on Brain Network Dynamics: A Cross-Platform MEG Study

Neural fingerprinting seeks to identify individuals based on measurements of brain activity, exploiting the fact that aspects of brain function unique to an individual remain stable across repeated scans. Magnetoencephalography (MEG) is a powerful technique for fingerprinting. However, most MEG studies have used conventional (SQUID-based) MEG technology and typically rely on data aggregated over time, overlooking the rich temporal dynamics available in MEG. Here, using SQUID-MEG and the more recently introduced OPM-MEG, we showed fingerprinting was possible within and between modalities using static (time-aggregated) features; this is consistent with previous work. We further asked whether fingerprinting was possible based on network dynamics, estimated using a canonical hidden Markov model (CHMM). Results showed that the CHMM-derived networks provide a better fit to SQUID data than to OPM data; however, this effect was small and to be expected given the canonical networks were trained on SQUID data. We further showed that fingerprinting was possible within and between modalities using CHMM-derived state activation time courses and state power spectral densities. However, state summary statistics and transition probabilities only supported within modality fingerprinting. Our findings suggest that subject-specific information is preserved within CHMM states and across MEG technologies. This represents an important step towards advancing our understanding of brain dynamics, and particularly the brain networks delineated by the CHMM. The study also supports the future use of the CHMM for processing and interpretation of OPM-MEG data.

neuroscience↗

bioRxiv2026

Intracranial Validation of Magnetoencephalography Across Oscillatory Frequency and Depth

Non-invasive, whole-brain neuroimaging methods such as functional magnetic resonance imaging, electroencephalography (EEG), and magnetoencephalography (MEG) are essential tools for studying the basis of human cognition in health and disease. MEG offers the opportunity to study neural activity at its intrinsic timescale, by recording the magnetic fields generated by electrical currents within the brain from outside the skull. Moreover, recently developed optically pumped magnetometers (OPMs) allow these recordings to take place in new settings, for example during naturalistic behaviour and in previously inaccessible populations. These breakthroughs have led to a shift in the neuroimaging landscape, with a global increase in the adoption of MEG. Crucially, however, the extent to which MEG recordings can measure different features of neural activity remains unclear. To address this issue, we leveraged a unique and rare dataset of concurrent MEG and intracranial EEG recordings from a cohort of epileptic patients. We found that group-level inferences of spontaneous oscillatory dynamics made with source-localised MEG, i.e. estimates of power and bursts, accurately reflected the underlying neural activity. As expected, the agreement was strongest for lower-frequency activity (delta, theta, and alpha) and superficial sources, and weakest in the gamma range. Crucially, however, MEG was also sensitive to deep structures: it captured oscillatory power and burst dynamics in the hippocampus, most robustly in the theta band. These findings demonstrate that MEG is sensitive to physiologically meaningful activity in cortical and subcortical regions and establish a foundation for the interpretation of future MEG studies across a wide range of research domains.

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bioRxiv2025

Development of Replay-DMN Coordination Predicts Entorhinal Grid Codes

Neural replay, the reactivation of experience-related activity patterns during offline periods, has been implicated in organising memories into cognitive maps. However, how replay processes mature through childhood and adolescence remains unclear. Here we studied 106 participants aged 8-25 who learned a hidden two-dimensional (2D) associative structure and then underwent magnetoencephalography (MEG) during a map-based inference task and post-task rest to detect spontaneous replay. We found that during post-task rest, younger individuals relied primarily on replay alone to represent the 2D relationships, whereas older individuals showed increasingly precise timing alignment between replay events and activity in the default mode network (DMN), particularly when replay occurred at the trough of a DMN theta oscillation. Such replay-DMN coupling predicted the strength of a grid-cell-like code in the entorhinal cortex identified in this cohort with fMRI. Furthermore, resting-state fMRI revealed that DMN functional connectivity strengthened with age, in parallel with reduced reliance on replay and more efficient inference performance. These results reveal a developmental progression in which replay shifts from an isolated process in youth to a coordinated DMN mechanism by adulthood. This transition predicts the maturation of grid-like schema representations, shedding light on how children gradually build internal knowledge structures to support flexible inference.

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bioRxiv2024

Evidence for transient, uncoupled power and functional connectivity dynamics

There is growing interest in studying the temporal structure in brain network activity, in particular, dynamic functional connectivity (FC), which has been linked in several studies with cognition, demographics and disease states. The sliding window approach is one of the most common approaches to compute dynamic FC. However it cannot detect cognitively relevant and transient temporal changes at the time scales of fast cognition, i.e. on the order 100 milliseconds, which can be identified with model-based methods such as HMM (Hidden Markov Model) and DyNeMo (Dynamic Network Modes) using electrophysiology. These new methods provide time-varying estimates of the "power" (i.e. variance) and of the functional connectivity of the brain activity, under the assumption that they share the same dynamics. But there is no principled basis for this assumption. In this work, we propose Multi-dynamic Network Modes (M-DyNeMo), an extension to DyNeMo, that allows for the possibility that the power and the FC networks have different dynamics. Using this new method on magnetoencephalography (MEG) data, we show intriguingly that the dynamics of the power and the FC networks are uncoupled. Using a (visual) task MEG dataset, we also show that the power and FC network dynamics are modulated by the task, such that the coupling in their dynamics changes significantly during task. This new method reveals novel insights into evoked network responses and ongoing activity that previous methods fail to capture, challenging the assumption that power and FC share the same dynamics. HighlightsO_LIWe show that our proposed model - Multi-dynamic Network Modes (M-DyNeMo) - infers transient, uncoupled dynamics for time-varying variance (i.e. power) and functional connectivity (FC) in MEG data. C_LIO_LIM-DyNeMo infers plausible power and FC networks that are reproducible across different subjects, datasets, and parcellations. C_LIO_LIM-DyNeMo reveals task modulates the dynamics of the power and the FC networks, which induces a coupling between dynamics. C_LIO_LIThe evoked FC network response to a (visual) task is different to the evoked network response in power. C_LIO_LIThe datasets and scripts for performing all the analysis in this paper are made publicly available. C_LI

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bioRxiv2023

Impaired activation of the prefrontal executive network during working memory processing in multiple sclerosis

AbstractIn multiple sclerosis (MS), working memory (WM) impairment occurs soon after disease onset and significantly affects the patients quality of life. Functional imaging research in MS aims to investigate the neurophysiological underpinnings of WM impairment. In this context, we utilized a data-driven technique, the time delay embedded- hidden Markov model (TDE-HMM), to extract spectrally defined functional networks in magnetoencephalographic (MEG) data acquired during a WM visual-verbal n-back task. We observed that two networks show an altered activation in RR-MS patients. First, the activation of an early theta prefrontal network linked to stimulus encoding and attentional control significantly decreased in RR-MS compared to HC. This diminished activation correlated with reduced accuracy in task performance in the MS group, suggesting an impaired encoding and learning process. Secondly, a frontoparietal network characterized by beta coupling is activated between 300 and 600 ms after stimulus onset; this resembles the characteristic event-related P300, a cognitive marker extensively explored in EEG studies. The activation of this network is amplified in patients treated with benzodiazepine, in line with the well-known benzodiazepine-induced beta enhancement. Altogether, the TDE-HMM technique extracted task-relevant functional networks showing disease-specific and treatment- related alterations, revealing potential new markers to assess and track WM impairment in MS. HighlightsO_LIWe decomposed the brain dynamics underlying a WM n-back task in data-driven, spectrally defined whole-brain networks in both healthy controls and people with relapsing-remitting-MS (pwMS). C_LIO_LIPwMS showed a significantly decreased activation of an early theta prefrontal network linked to stimulus encoding and attentional control. C_LIO_LIThe weaker activation of this prefrontal theta network is correlated with worse task performance. C_LIO_LIA beta frontoparietal network with a P300-like temporal evolution was significantly modulated by the use of benzodiazepines. C_LIO_LIThe model distinguished disease-induced and treatment-induced dynamic network alterations. C_LI

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bioRxiv2023

Stacking models of brain dynamics improves prediction of subject traits in fMRI

Beyond structural and time-averaged functional connectivity brain measures, the way brain activity dynamically unfolds can add important information when investigating individual cognitive traits. One approach to leveraging this information is to extract features from models of brain network dynamics to predict individual traits. However, there are two potential sources of variation in the models estimation which will in turn affect the predictions: first, in certain cases, the estimation variability due to different initialisations or choice of inference method; and second, the variability induced by the choice of the model hyperparameters that determine the complexity of the model. Rather than merely being statistical noise, this variability may be useful in providing complementary information that can be leveraged to improve prediction accuracy. We propose stacking, a prediction-driven approach for model selection, to leverage this variability. Specifically, we combine predictions from multiple models of brain dynamics to generate predictions that are accurate and robust across multiple cognitive traits. We demonstrate the approach using the Hidden Markov Model, a probabilistic generative model of brain network dynamics. We show that stacking can significantly improve the prediction of subject-specific phenotypes, which is crucial for the clinical translation of findings.

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bioRxiv2023

A novel description of the network dynamics underpinning working memory

Working memory (WM) plays a central role in cognition, prompting neuroscientists to investigate its functional and structural substrates. The WM dynamic recruits large-scale frequency-specific brain networks that unfold over a few milliseconds - this complexity challenges traditional neuroimaging analyses. In this study, we unravel the WM network dynamics in an unsupervised, data-driven way, applying the time delay embedded-hidden Markov model (TDE-HMM). We acquired MEG data from 38 healthy subjects performing an n-back working memory task. The TDE-HMM model inferred four task-specific states with each unique temporal (activation), spectral (phase-coherence connections), and spatial (power spectral density distribution) profiles. A theta frontoparietal state performs executive functions, an alpha temporo-occipital state maintains the information, and a broad-band and spatially complex state with an M300 temporal profile leads the retrieval process and motor response. The HMM states can be straightforwardly interpreted within the neuropsychological multi-component model of WM, significantly improving the comprehensive description of WM. HighlightsO_LIWorking memory recruits different frequency-specific brain networks that wax and wane at a millisecond scale. C_LIO_LIThrough the time-delay embedded hidden (TDE-HMM) we are able to extract data-driven functional networks with unique spatial, spectral, and temporal profiles. C_LIO_LIWe demonstrate the existence of four task-specific brain networks that can be interpreted within the well-known Baddeleys multicomponent model of working memory. C_LIO_LIThis novel WM description unveils new features that will lead to a more in-depth characterization of cognitive processes in MEG data. C_LI

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bioRxiv2022

Multi-modal and multi-model interrogation of large-scale functional brain networks

Current whole-brain models are generally tailored to the modelling of a particular modality of data (e.g., fMRI or MEG/EEG). Although different imaging modalities reflect different aspects of neural activity, we hypothesise that this activity arises from common network dynamics. Building on the universal principles of self-organising delay-coupled nonlinear systems, we aim to link distinct electromagnetic and metabolic features of brain activity to the dynamics on the brains macroscopic structural connectome. To jointly predict dynamical and functional connectivity features of distinct signal modalities, we consider two large-scale models generating local short-lived 40 Hz oscillations with various degrees of realism - namely Stuart Landau (SL) and Wilson and Cowan (WC) models. To this end, we measure features of functional connectivity and metastable oscillatory modes (MOMs) in fMRI and MEG signals - and compare them against simulated data. We show that both models can represent MEG functional connectivity (FC) and functional connectivity dynamics (FCD) to a comparable degree, by varying global coupling and mean conduction time delay. For both models, the omission of delays dramatically decreased the performance. For fMRI, the SL model performed worse for FCD, highlighting the importance of balanced dynamics for the emergence of spatiotemporal patterns of ultra-slow dynamics. Notably, optimal working points varied across modalities and no model was able to achieve a correlation with empirical FC higher than 0.45 across modalities for the same set of parameters. Nonetheless, both displayed the emergence of FC patterns beyond the anatomical framework. Finally, we show that both models can generate MOMs with empirical-like properties. Our results demonstrate the emergence of static and dynamic properties of neural activity at different timescales from networks of delay-coupled oscillators at 40 Hz. Given the higher dependence of simulated FC on the underlying structural connectivity, we suggest that mesoscale heterogeneities in neural circuitry may be critical for the emergence of parallel cross-modal functional networks and should be accounted for in future modelling endeavours.

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bioRxiv2022

Mixtures of large-scale dynamic functional brain network modes

Accurate temporal modelling of functional brain networks is essential in the quest for understanding how such networks facilitate cognition. Researchers are beginning to adopt time-varying analyses for electrophysiological data that capture highly dynamic processes on the order of milliseconds. Typically, these approaches, such as clustering of functional connectivity profiles and Hidden Markov Modelling (HMM), assume mutual exclusivity of networks over time. Whilst a powerful constraint, this assumption may be compromising the ability of these approaches to describe the data effectively. Here, we propose a new generative model for functional connectivity as a time-varying linear mixture of spatially distributed statistical "modes". The temporal evolution of this mixture is governed by a recurrent neural network, which enables the model to generate data with a rich temporal structure. We use a Bayesian framework known as amortised variational inference to learn model parameters from observed data. We call the approach DyNeMo (for Dynamic Network Modes), and show using simulations it outperforms the HMM when the assumption of mutual exclusivity is violated. In resting-state MEG, DyNeMo reveals a mixture of modes that activate on fast time scales of 100-150 ms, which is similar to state lifetimes found using an HMM. In task MEG data, DyNeMo finds modes with plausible, task-dependent evoked responses without any knowledge of the task timings. Overall, DyNeMo provides decompositions that are an approximate remapping of the HMMs while showing improvements in overall explanatory power. However, the magnitude of the improvements suggests that the HMMs assumption of mutual exclusivity can be reasonable in practice. Nonetheless, DyNeMo provides a flexible framework for implementing and assessing future modelling developments.

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bioRxiv2021

Spatiotemporally Resolved Multivariate Pattern Analysis for M/EEG

An emerging goal in neuroscience is tracking what information is represented in brain activity over time as a participant completes some task. Whilst EEG and MEG offer millisecond temporal resolution of how activity patterns emerge and evolve, standard decoding methods present significant barriers to interpretability as they obscure the underlying spatial and temporal activity patterns. We instead propose the use of a generative encoding model framework that simultaneously infers the multivariate spatial patterns of activity and the variable timing at which these patterns emerge on individual trials. An encoding model inversion allows predictions to be made about unseen test data in the same way as in standard decoding methodology. These SpatioTemporally Resolved MVPA (STRM) models can be flexibly applied to a wide variety of experimental paradigms, including classification and regression tasks. We show that these models provide insightful maps of the activity driving predictive accuracy metrics; demonstrate behaviourally meaningful variation in the timing of pattern emergence on individual trials; and achieve predictive accuracies that are either equivalent or surpass those achieved by more widely used methods. This provides a new avenue for investigating the brains representational dynamics and could ultimately support more flexible experimental designs in future. HIGHLIGHTSO_LIWe introduce SpatioTemporally Resolved MVPA (STRM), an approach that explicitly models how successive stages of stimulus processing are distributed in both space and time in M/EEG data. C_LIO_LIWe show that STRM is broadly applicable to diverse types of M/EEG data and outputs meaningful and interpretable maps of how neural representations evolve in space and time at millisecond resolution. C_LIO_LIThe trial-specific deviations in activity pattern timings identified by STRM are not random, but vary systematically with inter-trial differences in behavioural, cognitive and physiological variables. C_LIO_LIThese methods result in predictive accuracy metrics that are mostly equivalent to, or a modest improvement on, conventional methods. C_LI

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bioRxiv2021

Data and model considerations for estimating time-varying functional connectivity in fMRI

Functional connectivity (FC) in the brain has been shown to exhibit subtle but reliable modulations within a session. One way of estimating time-varying FC is by using state-based models that describe fMRI time series as temporal sequences of states, each with an associated, characteristic pattern of FC. However, the estimation of these models from data sometimes fails to capture changes in a meaningful way, such that the model estimation assigns entire sessions (or the largest part of them) to a single state, therefore failing to capture within-session state modulations effectively; we refer to this phenomenon as the model becoming static, or model stasis. Here, we aim to quantify how the nature of the data and the choice of model parameters affect the models ability to detect temporal changes in FC using both simulated fMRI time courses and resting state fMRI data. We show that large between-subject FC differences can overwhelm subtler within-session modulations, causing the model to become static. Further, the choice of parcellation can also affect the models ability to detect temporal changes. We finally show that the model often becomes static when the number of free parameters that need to be estimated is high and the number of observations available for this estimation is low in comparison. Based on these findings, we derive a set of practical recommendations for time-varying FC studies, in terms of preprocessing, parcellation and complexity of the model. HighlightsO_LITime-varying FC models sometimes fail to detect temporal changes in fMRI data C_LIO_LIBetween- and within-subject FC variability affect model stasis C_LIO_LIThe choice of parcellation affects model stasis in real fMRI data C_LIO_LIThe number of observations and free parameters critically affect model stasis Keywords: fMRI; time-varying FC; Hidden Markov Model (HMM); resting state C_LI

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bioRxiv2021

Modulations of local synchrony over time lead to resting-state functional connectivity in a parsimonious large-scale brain model

Biophysical models of large-scale brain activity are a fundamental tool for understanding the mechanisms underlying the patterns observed with neuroimaging. These models combine a macroscopic description of the within- and between-ensemble dynamics of neurons within a single architecture. A challenge for these models is accounting for modulations of within-ensemble synchrony over time. Such modulations in local synchrony are fundamental for modeling behavioral tasks and resting-state activity. Another challenge comes from the difficulty in parametrizing large scale brain models which hinders researching principles related with between-ensembles differences. Here we derive a parsimonious large scale brain model that can describe fluctuations of local synchrony. Crucially, we do not reduce within-ensemble dynamics to macroscopic variables first, instead we consider within and between-ensemble interactions similarly while preserving their physiological differences. The dynamics of within-ensemble synchrony can be tuned with a parameter which manipulates local connectivity strength. We simulated resting-state static and time-resolved functional connectivity of alpha band envelopes in models with identical and dissimilar local connectivities. We show that functional connectivity emerges when there are high fluctuations of local and global synchrony simultaneously (i.e. metastable dynamics). We also show that for most ensembles, leaning towards local asynchrony or synchrony correlates with the functional connectivity with other ensembles, with the exception of some regions belonging to the default-mode network. Author summaryHere we present and evaluate a parsimonious model of large-scale brain activity. The model represents the brain as a network-of-networks structure. The sub-networks describe the neural activity within a brain region, and the global network encodes interactions between brain regions. Unlike other models, it capture progressive changes of local synchrony and local dynamics can be tuned with one parameter. Therefore the model could be used not only to model resting-state, but also behavioural tasks. Furthermore, we describe a simple framework that can deal with the arduous task of identifying global and local parameters.

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bioRxiv2018

Functional network dynamics in a neurodevelopmental disorder of known genetic origin

Cognitive processing depends on the temporal co-ordination of functional brain networks. This fundamental aspect of neurophysiology potentially bridges the genetic regulation of neuronal activity and developmental cognitive impairments. We investigated brain network dynamics in a neurodevelopmental disorder of known genetic origin, by comparing individuals with ZDHHC9-associated intellectual disability to individuals with no known impairment. We used Hidden Markov Modelling on magnetoencephalography (MEG) data, at rest and during auditory oddball stimulation, to characterise transient network dynamics. At rest, network dynamics distinguished the groups, with ZDHHC9 participants showing longer state activation. Crucially, ZDHHC9 gene expression levels predicted the group differences across networks, supporting an association between molecular pathology and neurophysiology. In contrast, network dynamics during auditory oddball stimulation did not show this association. We demonstrate a link between brain network dynamics and regional gene expression, and present a valuable method for understanding the real-time neural mechanisms linking genetic variation to cognitive difficulties.

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bioRxiv2018

Transient spectral events in resting state MEG predict individual time-frequency task responses

Even in response to apparently simple tasks such as hand moving, human brain activity shows remarkable inter-subject variability. Presumably, this variability reflects genuine behavioural or functional variability. Recently, spatial variability of resting-state features in fMRI - specifically connectivity - has been shown to explain (spatial) task-response variability. Such a link, however, is still missing for M/EEG data and its spectrally rich structure. At the same time, it has recently been shown that task responses in M/EEG can be well represented using transient spectral events bursting at fast time scales. Here, we show that individual differences in the spatio-spectral structure of M/EEG task responses, can, to a reasonable degree, be predicted from individual differences in transient spectral events identified at rest. In a MEG dataset of diverse task conditions (including motor responses, working memory and language comprehension tasks) and resting-state sessions for each subject (n = 89), we used Hidden-Markov-Modelling to identify transient spectral events as a feature set to learn the mapping of space-time-frequency content from rest to task. Resulting trial-averaged, subject-specific task-response predictions were then compared with the actual task responses in left-out subjects. All task conditions were predicted significantly above chance. Furthermore, we observed a systematic relationship between genetic similarity (e.g. unrelated subjects vs. twins) and predictability. These findings support the idea that subject-specific transient spectral events in resting-state neural activity are linked to, and predictive of, subject-specific trial-averaged task responses in a wide range of experimental conditions.

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bioRxiv2018

Spontaneous network activity accounts for variability in stimulus-induced gamma responses

Gamma range activity in human visual cortex is believed to play a major role in cognitive functions, such as selective attention. Although recent studies have revealed substantial variability in gamma activity, its origins are still unclear.\n\nWe investigated whether variability in stimulus-induced gamma activity is related to the spontaneous dynamics of resting-state networks using Hidden Markov Modelling. The magnetoencephalogram (MEG) of 15 healthy participants was recorded at rest and while they were performing a task involving a visual stimulus inducing strong, narrow-band gamma activity. Brain states were inferred from the tasks baseline periods and from resting-state recordings, respectively.\n\nOur results show how network states are related to the amplitude of stimulus-induced gamma responses. Across trials, we found an association between the amplitude of gamma responses and the brain state occurring immediately prior to stimulus presentation. Strong gamma responses followed a state characterized by prominent delta/theta oscillations in parieto-occipital regions and comparably weak alpha activity. Across subjects, the overall probability of visiting this state in the baseline period, i.e. the individual preference for this state, correlated positively with the amplitude of the trial-averaged gamma response. Remarkably, this relationship persisted when states were inferred from resting-state recordings rather than the tasks baseline.\n\nIn summary, both within- and across-subject variability in stimulus-induced gamma activity can in part be explained by the ongoing dynamics of whole-brain network states. Fast, pre-stimulus modulations of brain states account for differences between trials while stable, individual state preferences account for differences between subjects.

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bioRxiv2016

Single or Multi-Frequency Generators in On-going Brain Activity: a Mechanistic Whole-Brain Model following empirical MEG evidences

During rest, envelopes of band-limited on-going MEG signals co-vary across the brain in consistent patterns, which have been related to resting-state networks measured with fMRI. To investigate the genesis of such envelope correlations, we consider a whole-brain network model assuming two distinct fundamental scenarios: one where each brain area generates oscillations in a single frequency, and a novel one where each brain area can generate oscillations in multiple frequency bands. The models share, as a common generator of damped oscillations, the normal form of a supercritical Hopf bifurcation operating at the critical border between the steady state and the oscillatory regime. The envelopes of the simulated signals are compared with empirical MEG data using new methods to analyse the envelope dynamics in terms of their phase coherence and stability across the spectrum of carrier frequencies.\n\nConsidering the whole-brain model with a single frequency generator in each brain area, we obtain the best fit with the empirical MEG data when the fundamental frequency is tuned at 12Hz. However, when multiple frequency generators are placed at each local brain area, we obtain an improved fit of the spatio-temporal structure of on-going MEG data across all frequency bands. Our results indicate that the brain is likely to operate on multiple frequency channels during rest, introducing a novel dimension for future models of large-scale brain activity.

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