Publications of Christophe Phillips
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See detailTimely sleep coupling: phase locked slow wave - spindle pairing is linked to AD neuropathology and forecasts cognitive decline
Chylinski, Daphné ULiege; Van Egroo, Maxime; Narbutas, Justinas ULiege et al

Conference (2021, November 19)

Alteration of sleep quality is a hallmark of the ageing process. The fine-tuned coalescence of elements of sleep microstructure seems to play a pivotal role in cognitive trajectories in ageing. This may ... [more ▼]

Alteration of sleep quality is a hallmark of the ageing process. The fine-tuned coalescence of elements of sleep microstructure seems to play a pivotal role in cognitive trajectories in ageing. This may be of prime clinical importance as a bidirectional detrimental relationship between sleep quality and Alzheimer’s disease (AD) neuropathology emerges in the literature and holds promise for novel sleep related interventions. However, sleep is not yet established as a true risk factor for AD, most likely because the understanding of its core associations with AD neuropathology remains insufficient. In this context, we focused on the timely coupling of two key graphoelements of Non-Rapid Eye Movement (NREM) sleep that is slow waves and spindles, and their associations with AD neuropathology and cognition. We show, in a detailed large dataset (N=100; 68 woman) of undisturbed sleep recorded in late middle-aged healthy individuals (50 to 70y; 60 +- 5), that the precise coupling of sleep spindles with a specific category of sleep slow waves, those deemed most important for memory consolidation, is associated to lower medial prefrontal cortex PET-scan β-Amyloid burden, a landmark of AD neuropathology (F1,96=6.2, p=0.014). Cruder aspects of sleep macrostructure and sleep intensity were, however, not significantly linked to β-Amyloid burden in this relatively young sample with low β-Amyloid deposit. We further show that this specific coupling is predictive of a lower memory decline, assessed over 2 years using a task highly sensitive to the first signs of memory impairment (F1,54=4.67, p=0.035). These findings unravel early links between sleep, AD-related and cognitive trajectories in ageing and suggest that altered coupling of sleep microstructure elements key to its functions could constitute the first association with AD neuropathology and that less refined measures of sleep macrostructure or sleep intensity may only be significantly associated to AD neuropathology later in life, when β-amyloid burden is higher. Sleep microstructure integrity could therefore constitute a potential indicator of a less successful ageing trajectory. [less ▲]

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See detailQuantitative MRI, EM head modelling and more: practical considerations and applications
Phillips, Christophe ULiege

Scientific conference (2021, November 03)

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See detailqMRI-BIDS: an extension to the brain imaging data structure for quantitative magnetic resonance imaging data
Karakuzu, Agah; Appelhoff, Stefan; Auer, Tibor et al

E-print/Working paper (2021)

The Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional ... [more ▼]

The Brain Imaging Data Structure (BIDS) established community consensus on the organization of data and metadata for several neuroimaging modalities. Traditionally, BIDS had a strong focus on functional magnetic resonance imaging (MRI) datasets and lacked guidance on how to store multimodal structural MRI datasets. Here, we present and describe the BIDS Extension Proposal 001 (BEP001), which adds a range of quantitative MRI (qMRI) applications to the BIDS. In general, the aim of qMRI is to characterize brain microstructure by quantifying the physical MR parameters of the tissue via computational, biophysical models. By proposing this new standard, we envision standardization of qMRI which makes multicenter dissemination of interoperable data possible. As a result, BIDS can act as a catalyst of convergence between qMRI methods development and application-driven neuroimaging studies that can help develop quantitative biomarkers for neural tissue characterization. Finally, our BIDS extension offers a common ground for developers to exchange novel imaging data and tools, reducing the practical barriers to standardization that is currently lacking in the field of neuroimaging. [less ▲]

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See detailExploratory radiomic analysis of conventional versus quantitative brain MRI: Towards automatic diagnosis of early multiple sclerosis
Lavrova, Elizaveta ULiege; LOMMERS, Emilie ULiege; WOODRUFF, Henry et al

in Frontiers in Neuroscience (2021)

Conventional magnetic resonance imaging (cMRI) is poorly sensitive to pathological changes related to multiple sclerosis (MS) in normal-appearing white matter (NAWM) and grey matter (GM), with the added ... [more ▼]

Conventional magnetic resonance imaging (cMRI) is poorly sensitive to pathological changes related to multiple sclerosis (MS) in normal-appearing white matter (NAWM) and grey matter (GM), with the added difficulty of not being very reproducible. Quantitative MRI (qMRI) on the other hand attempts to represent physical properties of tissues, making it an ideal candidate for quantitative medical image analysis, or radiomics. We therefore hypothesized that qMRI-based radiomic features have added diagnostic value in MS compared to cMRI. This study investigated the ability of cMRI (T1w) and qMRI features extracted from WM, NAWM, and GM to distinguish between MS patients (MSP) and healthy control subjects (HCS). We developed exploratory radiomic classification models on a dataset comprising 36 MSP and 36 HCS recruited in CHU Liege, Belgium, acquired with cMRI and qMRI. For each image type and region of interest, qMRI radiomic models for MS diagnosis were developed on a training subset and validated on a testing subset. Radiomic models based on cMRI were developed on the entire training dataset and externally validated on open-source datasets with 167 HCS and 10 MSP. Ranked by region of interest, the best diagnostic performance was achieved in the whole WM. Here the model based on magnetization transfer imaging (a type of qMRI) features yielded a median area under the receiver operating characteristic curve (AUC) of 1.00 in the testing sub-cohort. Ranked by image type, the best performance was achieved by the magnetization transfer models, with median AUCs of 0.79 (0.69-0.90 90% CI) in NAWM and 0.81 (0.71-0.90) in GM. External validation of the T1w models yielded an AUC of 0.78 (0.47-1.00) in whole WM, demonstrating a large 95% CI and low sensitivity of 0.30 (0.10-0.70). This exploratory study indicates that qMRI Radiomics could provide efficient diagnostic information using NAWM and GM analysis in MSP. T1w radiomics could be useful for a fast and automated check of conventional MRI for WM abnormalities once acquisition and reconstruction heterogeneities have been overcome. Further prospective validation is needed involving more data for better interpretation and generalization of the results. [less ▲]

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See detailShamo v1.0 - Stochastic electromagnetic head modelling made easy
Grignard, Martin ULiege; Geuzaine, Christophe ULiege; Phillips, Christophe ULiege

Poster (2021, June)

We introduce a Python 3 package: “shamo”. It can perform mesh generation, electromagnetic simulations and sensitivity analysis.

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See detailTime course of cortical response complexity during extended wakefulness and its differential association with vigilance in young and older individuals
Gaggioni, Giulia ULiege; Shumbayawonda, Elizabeth; Montanaro, Umberto et al

in Biochemical Pharmacology (2021), epub ahead of print

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See detailshamo: A tool for electromagnetic modelling, simulation and sensitivity analysis of the head
Grignard, Martin ULiege; Geuzaine, Christophe ULiege; Phillips, Christophe ULiege

E-print/Working paper (2021)

Accurate electromagnetic modelling of the head of a subject is of main interest in the fields of source reconstruction and brain stimulation. Those processes rely heavily on the quality of the model and ... [more ▼]

Accurate electromagnetic modelling of the head of a subject is of main interest in the fields of source reconstruction and brain stimulation. Those processes rely heavily on the quality of the model and, even though the geometry of the tissues can be extracted from magnetic resonance images (MRI) or computed tomography (CT), their physical properties such as the electrical conductivity are hard to measure with non intrusive techniques. In this paper, we propose a tool to assess the uncertainty in the model parameters as well as compute a parametric electroencephalography (EEG) forward solution and current distribution for transcranial direct current stimulation (tDCS). [less ▲]

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See detailRestoring statistical validity in group analyses of motion-corrupted MRI data
Lutti, Antoine; Corbin, Nadège; Ashburner, John et al

E-print/Working paper (2021)

Motion during the acquisition of magnetic resonance imaging (MRI) data degrades image quality, hindering our capacity to characterize disease in patient populations. Quality control procedures allow the ... [more ▼]

Motion during the acquisition of magnetic resonance imaging (MRI) data degrades image quality, hindering our capacity to characterize disease in patient populations. Quality control procedures allow the exclusion of the most affected images from analysis. However, the criterion for exclusion is difficult to determine objectively and exclusion can lead to a suboptimal compromise between image quality and sample size. We provide an alternative, data-driven solution that assigns weights to each image, computed from an index of image quality using restricted maximum likelihood. We illustrate this method through the analysis of brain MRI data. The proposed method restores the validity of statistical tests, and performs near optimally in all brain regions, despite local effects of head motion. This method is amenable to the analysis of a broad type of MRI data and can accommodate any measure of image quality. [less ▲]

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See detailPositive Effect of Cognitive Reserve on Episodic Memory, Executive and Attentional Functions Taking Into Account Amyloid-Beta, Tau, and Apolipoprotein E Status
Narbutas, Justinas ULiege; Chylinski, Daphné ULiege; Van Egroo, Maxime et al

in Frontiers in Aging Neuroscience (2021), 13

Studies exploring the simultaneous influence of several physiological and environmental factors on domain-specific cognition in late middle-age remain scarce. Therefore, our objective was to determine the ... [more ▼]

Studies exploring the simultaneous influence of several physiological and environmental factors on domain-specific cognition in late middle-age remain scarce. Therefore, our objective was to determine the respective contribution of modifiable risk/protective factors (cognitive reserve and allostatic load) on specific cognitive domains (episodic memory, executive functions, and attention), taking into account non-modifiable factors [sex, age, and genetic risk for Alzheimer’s disease (AD)] and AD-related biomarker amount (amyloid-beta and tau/neuroinflammation) in a healthy late-middle-aged population. One hundred and one healthy participants (59.4 ± 5 years; 68 women) were evaluated for episodic memory, executive and attentional functioning via neuropsychological test battery. Cognitive reserve was determined by the National Adult Reading Test. The allostatic load consisted of measures of lipid metabolism and sympathetic nervous system functioning. The amyloid-beta level was assessed using positron emission tomography in all participants, whereas tau/neuroinflammation positron emission tomography scans and apolipoprotein E genotype were available for 58 participants. Higher cognitive reserve was the main correlate of better cognitive performance across all domains. Moreover, age was negatively associated with attentional functioning, whereas sex was a significant predictor for episodic memory, with women having better performance than men. Finally, our results did not show clear significant associations between performance over any cognitive domain and apolipoprotein E genotype and AD biomarkers. This suggests that domain-specific cognition in late healthy midlife is mainly determined by a combination of modifiable (cognitive reserve) and non-modifiable factors (sex and age) rather than by AD biomarkers and genetic risk for AD. [less ▲]

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See detailAssociations between cognitive complaints, memory performance, mood and amyloid-β accumulation in healthy amyloid negative late-midlife individuals
Narbutas, Justinas ULiege; Van Egroo, Maxime; Chylinski, Daphné ULiege et al

in Journal of Alzheimer's Disease (2021), 83

Background. Cognitive complaints are gaining more attention as they may represent an early marker of increased risk for AD in individuals without objective decline at standard neuropsychological ... [more ▼]

Background. Cognitive complaints are gaining more attention as they may represent an early marker of increased risk for AD in individuals without objective decline at standard neuropsychological examination. Objective. Our aim was to assess whether cognitive complaints in late middle-aged individuals not seeking medical help are related to objective cognitive outcomes known as early markers for AD risk, concomitant affective state, and amyloid-β (Aβ) burden. Methods. Eighty-seven community-based cognitively normal individuals aged 50-69 years underwent neuropsychological assessment for global cognition, using Preclinical Alzheimer’s Cognitive Composite 5 (PACC5) score, and a more specific episodic memory measure. Affective state was based on self-assessment questionnaires for depression and anxiety. Aβ PET burden was assessed via [18F]Flutemetamol (N=84) and [18F]Florbetapir (N=3) uptake. Cognitive complaints were evaluated using Cognitive Difficulties Scale. Results. Higher cognitive complaints were significantly associated with lower episodic memory performance and worse affective state. Moreover, higher level of cognitive complaints was related to higher (but still sub-clinical) global Aβ accumulation (at uncorrected significance level). Importantly, all three aspects remained significant when taken together in the same statistical model, indicating that they explained distinct parts of variance. Conclusion. In healthy Aβ negative late middle-aged individuals, a higher degree of cognitive complaints is associated with lower episodic memory efficiency, more anxiety and depression, as well as, potentially, with higher Aβ burden, suggesting that complaints might signal subtle decline. Future studies should untangle how cognitive complaints in healthy aging populations are related to longitudinal changes in objective cognition and AD biomarker correlates. [less ▲]

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See detailEarly brainstem [18F]THK5351 uptake is linked to cortical hyper-excitability in healthy aging
Van Egroo, Maxime; Chylinski, Daphné ULiege; Narbutas, Justinas ULiege et al

in JCI Insight (2021), 6(2), 142514

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See detailshamo
Grignard, Martin ULiege; Geuzaine, Christophe ULiege; Phillips, Christophe ULiege

Software (2020)

Constructing accurate subject specific head model is of main interest in the fields of source imaging (EEG/MEG) and brain stimulation (tDCS/tMS). shamo is an open source python package to calculate EEG ... [more ▼]

Constructing accurate subject specific head model is of main interest in the fields of source imaging (EEG/MEG) and brain stimulation (tDCS/tMS). shamo is an open source python package to calculate EEG leadfields, current flows, and electric potential distribution in the head. From a labelled 3D image of the head, the whole process is fully automatized, relying only on a few parameter files, e.g. conductivities (including white matter anisotropy) plus source and electrode locations. Since there is no non-invasive method to measure the electromagnetic (EM) properties of the head tissues, shamo can also be used to assess the sensitivity of the EM head model to these parameters. [less ▲]

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See detailEarly brainstem [18F]THK5351 uptake is linked to cortical hyper-excitability in healthy aging
Van Egroo, Maxime ULiege; Chylinski, Daphné ULiege; Narbutas, Justinas ULiege et al

in JCI Insight (2020), Online ahead of print

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See detailArousals during sleep are associated with cortical amyloid-β burden and cognition in healthy older adults
Chylinski, Daphné ULiege; Van Egroo, Maxime ULiege; Narbutas, Justinas ULiege et al

Conference (2020, September 22)

Arousals during sleep have been studied in sleep pathologies such as sleep apnoea and periodic limb movement disorder, or in interventional experimental protocols triggering arousals through external ... [more ▼]

Arousals during sleep have been studied in sleep pathologies such as sleep apnoea and periodic limb movement disorder, or in interventional experimental protocols triggering arousals through external stimulations (mainly noise). Those studies generally pointed towards a detrimental role of arousals. Yet, the causes and consequences of spontaneous arousals in healthy individuals remain largely unknown. Recently, a bidirectional detrimental link between sleep-wake dysfunction and the pathogenesis of Alzheimer’s disease is emerging in the literature, including the abnormal accumulation of amyloid-β (Aβ) and tau protein in the brain. Here, we investigated whether spontaneous arousals during sleep were associated with Aβ and tau burden, as well as with cognitive performance. We recorded night-time sleep of 101 cognitively normal older individuals devoid of sleep disorders (aged 51-69; mean 59 ± 5; 68 females) under EEG. We assessed 18F-flutemetamol and 18F-THK 5351 regional brain uptake using Positron Emission Tomography to infer their level of Aβ and tau protein burden, respectively. Validated automatic arousal detection was computed on all EEG recordings. All participants completed an extensive cognitive battery of neuropsychological tasks to assess memory, attentional, and executive functioning while well-rested. Generalised linear mixed models analyses revealed that arousals concomitant to a muscular tone increase (arousals EMG) are significantly negatively associated with Aβ burden in the cortex (F(1,95) = 11.62, p = .001), while correcting for age, sex and total sleep time, whereas no such relationship was observed for tau (p = .47). Furthermore, global cognitive performances were positively linked with arousals EMG throughout the night (F(1,95) = 6.38, p = .01), the observed relationship being mainly driven by performances in the attentional (p = .005) and executive domain (p = .04), after adjusting for age, sex, education and total sleep time. These findings suggest arousals during sleep may form a heterogeneous category of events composed of arousals evoked by external or pathological event, that may be deleterious, and spontaneous arousals that may be associated with better brain structure or cognition. Future research should try to further characterise arousal events to disentangle what has been so far taring everyone with the same brush. [less ▲]

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