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Marc Goodfellow

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6 papers
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6

YNIMG Journal 2022 Journal Article

Using deep clustering to improve fMRI dynamic functional connectivity analysis

  • Arthur P.C. Spencer
  • Marc Goodfellow

Dynamic functional connectivity (dFC) analysis of resting-state fMRI data is commonly performed by calculating sliding-window correlations (SWC), followed by k-means clustering in order to assign each window to a given state. Studies using synthetic data have shown that k-means performance is highly dependent on sliding window parameters and signal-to-noise ratio. Additionally, sources of heterogeneity between subjects may affect the accuracy of group-level clustering, thus affecting measurements of dFC state temporal properties such as dwell time and fractional occupancy. This may result in spurious conclusions regarding differences between groups (e.g. when comparing a clinical population to healthy controls). Therefore, is it important to quantify the ability of k-means to estimate dFC state temporal properties when applied to cohorts of multiple subjects, and to explore ways in which clustering performance can be maximised. Here, we explore the use of dimensionality reduction methods prior to clustering in order to map high-dimensional data to a lower dimensional space, providing salient features to the subsequent clustering step. We assess the use of deep autoencoders for dimensionality reduction prior to applying k-means clustering to the encoded data. We compare this deep clustering method to dimensionality reduction using principle component analysis (PCA), uniform manifold approximation and projection (UMAP), as well as applying k-means to the original feature space using either L1 or L2 distance. We provide extensive quantitative evaluation of clustering performance using synthetic datasets, representing data from multiple heterogeneous subjects. In synthetic data we find that deep clustering gives the best performance, while other approaches are often insufficient to capture temporal properties of dFC states. We then demonstrate the application of each method to real-world data from human subjects and show that the choice of dimensionality reduction method has a significant effect on group-level measurements of state temporal properties.

YNICL Journal 2021 Journal Article

Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy

  • Arthur P.C. Spencer
  • Jonathan C.W. Brooks
  • Naoki Masuda
  • Hollie Byrne
  • Richard Lee-Kelland
  • Sally Jary
  • Marianne Thoresen
  • James Tonks

Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.

YNICL Journal 2021 Journal Article

Motor function and white matter connectivity in children cooled for neonatal encephalopathy

  • Arthur P.C. Spencer
  • Jonathan C.W. Brooks
  • Naoki Masuda
  • Hollie Byrne
  • Richard Lee-Kelland
  • Sally Jary
  • Marianne Thoresen
  • Marc Goodfellow

Therapeutic hypothermia reduces the incidence of severe motor disability, such as cerebral palsy, following neonatal hypoxic-ischaemic encephalopathy. However, cooled children without cerebral palsy at school-age demonstrate motor deficits and altered white matter connectivity. In this study, we used diffusion-weighted imaging to investigate the relationship between white matter connectivity and motor performance, measured using the Movement Assessment Battery for Children-2, in children aged 6-8 years treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy at birth, who did not develop cerebral palsy (cases), and matched typically developing controls. Correlations between total motor scores and diffusion properties in major white matter tracts were assessed in 33 cases and 36 controls. In cases, significant correlations (FDR-corrected P < 0.05) were found in the anterior thalamic radiation bilaterally (left: r = 0.513; right: r = 0.488), the cingulate gyrus part of the left cingulum (r = 0.588), the hippocampal part of the left cingulum (r = 0.541), and the inferior fronto-occipital fasciculus bilaterally (left: r = 0.445; right: r = 0.494). No significant correlations were found in controls. We then constructed structural connectivity networks, for 22 cases and 32 controls, in which nodes represent brain regions and edges were determined by probabilistic tractography and weighted by fractional anisotropy. Analysis of whole-brain network metrics revealed correlations (FDR-corrected P < 0.05), in cases, between total motor scores and average node strength (r = 0.571), local efficiency (r = 0.664), global efficiency (r = 0.677), clustering coefficient (r = 0.608), and characteristic path length (r = -0.652). No significant correlations were found in controls. We then investigated edge-level association with motor function using the network-based statistic. This revealed subnetworks which exhibited group differences in the association between motor outcome and edge weights, for total motor scores (P = 0.0109) as well as for balance (P = 0.0245) and manual dexterity (P = 0.0233) domain scores. All three of these subnetworks comprised numerous frontal lobe regions known to be associated with motor function, including the superior frontal gyrus and middle frontal gyrus. The subnetwork associated with total motor scores was highly left-lateralised. These findings demonstrate an association between impaired motor function and brain organisation in school-age children treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy.

YNIMG Journal 2017 Journal Article

Temporally correlated fluctuations drive epileptiform dynamics

  • Maciej Jedynak
  • Antonio J. Pons
  • Jordi Garcia-Ojalvo
  • Marc Goodfellow

Macroscopic models of brain networks typically incorporate assumptions regarding the characteristics of afferent noise, which is used to represent input from distal brain regions or ongoing fluctuations in non-modelled parts of the brain. Such inputs are often modelled by Gaussian white noise which has a flat power spectrum. In contrast, macroscopic fluctuations in the brain typically follow a 1 / f b spectrum. It is therefore important to understand the effect on brain dynamics of deviations from the assumption of white noise. In particular, we wish to understand the role that noise might play in eliciting aberrant rhythms in the epileptic brain. To address this question we study the response of a neural mass model to driving by stochastic, temporally correlated input. We characterise the model in terms of whether it generates “healthy” or “epileptiform” dynamics and observe which of these dynamics predominate under different choices of temporal correlation and amplitude of an Ornstein-Uhlenbeck process. We find that certain temporal correlations are prone to eliciting epileptiform dynamics, and that these correlations produce noise with maximal power in the δ and θ bands. Crucially, these are rhythms that are found to be enhanced prior to seizures in humans and animal models of epilepsy. In order to understand why these rhythms can generate epileptiform dynamics, we analyse the response of the model to sinusoidal driving and explain how the bifurcation structure of the model gives rise to these findings. Our results provide insight into how ongoing fluctuations in brain dynamics can facilitate the onset and propagation of epileptiform rhythms in brain networks. Furthermore, we highlight the need to combine large-scale models with noise of a variety of different types in order to understand brain (dys-)function.

YNIMG Journal 2012 Journal Article

Self-organised transients in a neural mass model of epileptogenic tissue dynamics

  • Marc Goodfellow
  • Kaspar Schindler
  • Gerold Baier

Stimulation of human epileptic tissue can induce rhythmic, self-terminating responses on the EEG or ECoG. These responses play a potentially important role in localising tissue involved in the generation of seizure activity, yet the underlying mechanisms are unknown. However, in vitro evidence suggests that self-terminating oscillations in nervous tissue are underpinned by non-trivial spatio-temporal dynamics in an excitable medium. In this study, we investigate this hypothesis in spatial extensions to a neural mass model for epileptiform dynamics. We demonstrate that spatial extensions to this model in one and two dimensions display propagating travelling waves but also more complex transient dynamics in response to local perturbations. The neural mass formulation with local excitatory and inhibitory circuits, allows the direct incorporation of spatially distributed, functional heterogeneities into the model. We show that such heterogeneities can lead to prolonged reverberating responses to a single pulse perturbation, depending upon the location at which the stimulus is delivered. This leads to the hypothesis that prolonged rhythmic responses to local stimulation in epileptogenic tissue result from repeated self-excitation of regions of tissue with diminished inhibitory capabilities. Combined with previous models of the dynamics of focal seizures this macroscopic framework is a first step towards an explicit spatial formulation of the concept of the epileptogenic zone. Ultimately, an improved understanding of the pathophysiologic mechanisms of the epileptogenic zone will help to improve diagnostic and therapeutic measures for treating epilepsy.

YNIMG Journal 2011 Journal Article

Intermittent spike–wave dynamics in a heterogeneous, spatially extended neural mass model

  • Marc Goodfellow
  • Kaspar Schindler
  • Gerold Baier

Generalised epileptic seizures are frequently accompanied by sudden, reversible transitions from low amplitude, irregular background activity to high amplitude, regular spike–wave discharges (SWD) in the EEG. The underlying mechanisms responsible for SWD generation and for the apparently spontaneous transitions to SWD and back again are still not fully understood. Specifically, the role of spatial cortico-cortical interactions in ictogenesis is not well studied. We present a macroscopic, neural mass model of a cortical column which includes two distinct time scales of inhibition. This model can produce both an oscillatory background and a pathological SWD rhythm. We demonstrate that coupling two of these cortical columns can lead to a bistability between out-of-phase, low amplitude background dynamics and in-phase, high amplitude SWD activity. Stimuli can cause state-dependent transitions from background into SWD. In an extended local area of cortex, spatial heterogeneities in a model parameter can lead to spontaneous reversible transitions from a desynchronised background to synchronous SWD due to intermittency. The deterministic model is therefore capable of producing absence seizure-like events without any time dependent adjustment of model parameters. The emergence of such mechanisms due to spatial coupling demonstrates the importance of spatial interactions in modelling ictal dynamics, and in the study of ictogenesis.

v2026.09.13