Biology subjects

Jackson, G. D.

Publications and source records attributed to Jackson, G. D..

9 recordsLinked to original sources

bioRxiv2026

Multilayer Network Modelling of the Human Reading System

Reading is supported by rapid and flexible coordination of neural activity across distributed brain regions. We have previously shown that left fusiform gyrus (FusG) provides a bridge flexibly linking the visual form analysis required for reading with the language system. Here, we investigate the dynamic organisation of an extending reading network encompassing classical perisylvian language areas and FusG. We do so by applying multilayer network modelling to language fMRI data acquired through the Australian Epilepsy Project, using a paradigm that contrasts reading with visuospatial judgements. The dataset included 201 participants with left dominant language, both with and without seizure disorders. We hypothesised that the relative strength of dynamic inter-actions within this extended language network is associated with reading ability. Time resolved functional connectivity was estimated using a sliding window Pearsons correlation approach, and the resulting connectivity matrices were entered into a multilayer community detection algorithm to quantify spatiotemporal community structure within the reading network. We concentrate our analyses on allegiance, the probability that a pair of regions is assigned to the same community over time. Our results show that community structure within the reading network is characterised by a preference for within hemisphere assignment over cross hemisphere assignment, as well as higher nodal allegiance among left language regions compared with their right hemisphere homologues. As anticipated, within versus between network allegiance followed a similar gradient in both language and attention networks: lowest between left language and right attentional regions, intermediate between the left FusG and each respective network, and highest within-network (left language or right attention). Importantly, as hypothesised, reading ability was associated with FusG-inferior frontal gyrus (IFG) interactions: higher left FusG-left IFG allegiance correlated with better reading performance, whereas increased right FusG-left IFG allegiance correlated with poorer reading. These findings highlight hemispheric asymmetries in the dynamic organisation of the reading system and provide novel evidence linking individual differences in reading ability to network level dynamics. Our findings align with a developmental literature suggesting that as reading proficiency improves, there is a shift from bilateral to unilateral left occipitotemporal engagement.

neuroscience↗

bioRxiv2025

Robust-tedana: An automated denoising pipeline for multi-echo fMRI data

Multi-echo functional Magnetic Resonance Imaging (fMRI) data are acquired by recording image volumes at multiple echo times and can be used to improve the separation of neural activity from noise. TE-Dependent ANAlysis (tedana) is an open-source software tailored to denoising of multi-echo fMRI data. The efficacy of denoising can however be inconsistent, often necessitating manual inspection that precludes its application in large-scale studies where processing is ideally fully automated. Here, we introduce Robusttedana, an optimised denoising pipeline that achieves adequate results at both single-subject and group level. Robust-tedana incorporates Marchenko-Pastur Principal Component Analysis (MPPCA) for effective thermal noise reduction, robust independent component analysis for stabilised signal decomposition, and a modified component classification process. We evaluated its performance on Multi-Band Multi-Echo (MBME) language-task fMRI data from the Australian Epilepsy Project (AEP) using objective measures, comparing to conventional fMRI analysis with and without multi-echo-based denoising. Experts manual evaluation was undertaken on a subset of these data to validate the objective measures. The proposed pipeline both mitigates the prevalence of erroneous attenuation of genuine task activation due to instability of single-subject analysis, and increases the magnitude of group-wise effects. Robust-tedana therefore facilitates advanced analysis of MBME fMRI data in an automated pipeline, including for clinical research assessment of individuals.

bioengineering↗

bioRxiv2025

Common pitfalls during model specification in psychophysiological interaction analysis

Psychophysiological interaction (PPI) analysis is a widely used regression method in functional neuroimaging for capturing task-dependent changes in connectivity from a seed region. The present work identifies, and provides corrections for, common methodological pitfalls in PPI analysis that compromise model validity. Firstly, if the seed time series is extracted with prewhitening, the temporal structure of the signal is altered and subsequent deconvolution of prewhitened data becomes suboptimal. Furthermore, prewhitening again during model fitting results in double prewhitening of the seed regressor. Secondly, a failure to mean-centre the task regressor when calculating the interaction term can also lead to model misspecification and potentially spurious inferences. By using simulations and empirical language fMRI data from the Australian Epilepsy Project, we demonstrate the adverse effects of these issues, and how they are resolved when corrected. A systematic review of current practices revealed widespread model misspecification, and underreporting of methods, in published PPI studies. We provide clearer reporting guidelines, and advocate for appropriate methods for handling of prewhitening and mean-centring to ensure the validity of PPI analyses.

neuroscience↗

bioRxiv2021

Structural network alterations in focal and generalized epilepsy follow axes of epilepsy risk gene expression: An ENIGMA study

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem co-expression patterns of epilepsy risk genes. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1,328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-genetic signatures could guide diagnosis, and ultimately, tailor therapeutic approaches to specific epilepsy syndromes.

neuroscience↗

bioRxiv2021

Topographic divergence of atypical cortical asymmetry and regional atrophy patterns in temporal lobe epilepsy: a worldwide enigma study

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter pathology in TLE relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of TLE-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.

neuroscience↗

bioRxiv2020

Network-based atrophy modelling in the common epilepsies: a worldwide ENIGMA study

Epilepsy is increasingly conceptualized as a network disorder. In this cross-sectional mega-analysis, we integrated neuroimaging and connectome analysis to identify network associations with atrophy patterns in 1,021 adults with epilepsy compared to 1,564 healthy controls from 19 international sites. In temporal lobe epilepsy, areas of atrophy co-localized with highly interconnected cortical hub regions, whereas idiopathic generalized epilepsy showed preferential subcortical hub involvement. These morphological abnormalities were anchored to the connectivity profiles of distinct disease epicenters, pointing to temporo-limbic cortices in temporal lobe epilepsy and fronto-central cortices in idiopathic generalized epilepsy. Indices of progressive atrophy further revealed a strong influence of connectome architecture on disease progression in temporal lobe, but not idiopathic generalized, epilepsy. Our findings were reproduced across individual sites and single patients, and were robust across different analytical methods. Through worldwide collaboration in ENIGMA-Epilepsy, we provided novel insights into the macroscale features that shape the pathophysiology of common epilepsies.

neuroscience↗

bioRxiv2019

Reducing module size bias of participation coefficient

Both natural and engineered networks are often modular. Whether a network node interacts with only nodes from its own module or nodes from multiple modules provides insight into its functional role. The participation coeffcient (PC) is typically used to measure this attribute although its value also depends on the size of the module it belongs to, often leading to non-intuitive identification of highly connected nodes. Here, we develop a normalized PC that overcomes the module size bias associated with the conventional PC. Using brain, C.elegans, airport and simulated networks, we show that our measure of participation alleviates the module size bias, while preserving conceptual and mathematical properties, of the classic formulation of PC. Unlike the conventional PC, we identify London and New York as high participators in the air traffic network and demonstrate stronger associations with working memory in human brain networks, yielding new insights into nodal participation across network modules.

systems biology↗

bioRxiv2018

Brain connectivity dynamics: Multilayer network switching rate predicts brain performance

Large-scale brain dynamics measures repeating spatiotemporal connectivity patterns that reflect a range of putative different brain states that underlie the dynamic repertoire of brain functions. The role of transition between brain networks is poorly understood and whether switching between these states is important for behavior has been little studied. Our aim here is to model switching between functional brain networks using multilayer network methods and test for associations between model parameters and behavioral measures. We calculated time-resolved functional MRI (fMRI) connectivity from one-hour long data recordings in 1003 healthy human adults from the Human Connectome Project. The time-resolved fMRI connectivity data was used to generate a spatiotemporal multilayer modularity model enabling us to quantify network switching which we define as the rate at which each brain region transits between different fMRI networks. We found i) an inverse relationship between network switching and connectivity dynamics -defined as the difference in variance between time-resolved fMRI connectivity signals and phase randomized surrogates-; ii) brain connectivity was lower during intervals of network switching; iii) brain areas with frequent network switching had greater temporal complexity; iv) brain areas with high network switching were located in association cortices; and v) using cross-validated Elastic Net regression, network switching predicted inter-subject variation in working memory performance, planning/reasoning and amount of sleep. Our findings shed new light on the importance of brain dynamics predicting task performance and amount of sleep. The ability to switch between network configurations thus appears to be a fundamental feature of optimal brain function.

neuroscience↗

bioRxiv2017

On the relationship between instantaneous phase synchrony and correlation-based sliding windows for time-resolved fMRI connectivity analysis

Correlation-based sliding window analysis (CSWA) is the most commonly used method to estimate time-resolved functional MRI (fMRI) connectivity. However, instantaneous phase synchrony analysis (IPSA) is gaining popularity mainly because it offers single time-point resolution of time-resolved fMRI connectivity. We aim to provide a systematic comparison between these two approaches, on both temporal and topological levels.\n\nFor this purpose, we used resting-state fMRI data from two separate cohorts with different temporal resolutions (45 healthy subjects from Human Connectome Project fMRI data with repetition time of 0.72 s and 25 healthy subjects from a separate validation fMRI dataset with a repetition time of 3 s). For time-resolved functional connectivity analysis, we calculated tapered CSWA over a wide range of different window lengths that were temporally and topologically compared to IPSA.\n\nWe found a strong association in connectivity dynamics between IPSA and CSWA when considering the absolute values of CSWA. This association peaked at a CSWA window length of [~]20 seconds, irrespective of the sampling rate of the underlying fMRI data. Narrow-band filtering of fMRI data (0.03-0.07 Hz) yielded a stronger relationship between IPSA and CSWA than wider-band (0.01-0.1 Hz). On a topological level, time-averaged IPSA and CSWA nodes were non-linearly correlated, mainly because nodes with strong negative correlations (CSWA) displayed high phase synchrony (IPSA).\n\nOur results suggest that IPSA and CSWA provide comparable characterizations of time-resolved fMRI connectivity for appropriately chosen window lengths. Although IPSA requires narrow-band fMRI filtering, we recommend the use of IPSA given that it does not mandate a (semi-)arbitrary choice of window length and window overlap. A MATLAB code for calculating IPSA is provided.

neuroscience↗