Altered anterior default mode network dynamics in progressive multiple sclerosis

Giulia Bommarito, Younes Farouj, Maria Giulia Preti, Anjali Bagunu Tarun, Dimitri Nestor Alice Van De Ville
SAGE PUBLICATIONS LTD, 2021
Journal paper

Abstract

Background: Modifications in brain function remain relatively unexplored in progressive multiple sclerosis (PMS), despite their potential to provide new insights into the pathophysiology of the disease at this stage. Objectives: To characterize the dynamics of functional networks at rest in patients with PMS, and the relation with clinical disability. Methods: Thirty-two patients with PMS underwent clinical and cognitive assessment. The dynamic properties of functional networks, retrieved from transient brain activity, were obtained from patients and 25 healthy controls (HCs). Sixteen HCs and 19 patients underwent a 1-year follow-up (FU) clinical and imaging assessment. Differences in the dynamic metrics between groups, their longitudinal changes, and the correlation with clinical disability were explored. Results: PMS patients, compared to HCs, showed a reduced dynamic functional activation of the anterior default mode network (aDMN) and a decrease in its opposite-signed co-activation with the executive control network (ECN), at baseline and FU. Processing speed and visuo-spatial memory negatively correlated to aDMN dynamic activity. The anti-couplings between aDMN and auditory/sensory-motor network, temporal-pole/amygdala, or salience networks were differently associated with separate cognitive domains. Conclusion: Patients with PMS presented an altered aDMN functional recruitment and anti-correlation with ECN. The aDMN dynamic functional activity and interaction with other networks explained cognitive disability.

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Giulia Bommarito, Younes Farouj, Maria Giulia Preti, Anjali Bagunu Tarun, Dimitri Nestor Alice Van De Ville
SAGE PUBLICATIONS LTD, 2021
Journal paper

Abstract

Official source

https://infoscience.epfl.ch/record/287870?ln=en

About this result

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Speed has always been a critical consideration in magnetic resonance imaging (MRI), promising dramatic gains in imaging speed, a reduction in motion and susceptibility artifacts, and ultimately increased throughput for clinical studies. This thesis presents several new approaches to increase temporal resolution of a three dimensional (3D) echo planar imaging (EPI) sequence and explores the benefits of using high temporal resolution for both event-related brain activation and resting state networks fMRI studies. In the first approach, a new k-space traversal strategy for segmented 3D EPI is introduced which we termed as 3D reduced excitation EPI (3D RE-EPI). In this approach, two partitions are encoded per radio frequency (RF) excitation, effectively reducing the number of excitations used to acquire a 3D EPI dataset by a factor of two. With this strategy, whole-brain images with a nominal voxel size of 2mmisotropic could be acquired with a temporal resolution under half a second, using traditional parallel imaging acceleration upto 4x in the partition-encoding direction and using novel data acquisition speed-up of 2x. With 8x data acquisition speed-up in the partition-encoding direction, 3D RE-EPI produced acceptable image quality without introduction of noticeable additional artifacts. Due to increased temporal signal-to-noise ratio (tSNR) and better characterization of physiological fluctuations, the new strategy allowed detection of more resting state networks compared to standardmulti-slice two dimensional (2D) EPI and segmented 3D EPI. The approach above suffered from geometry factor (g-factor related) signal-to-noise ratio (SNR) losses, while using very high parallel imaging acceleration factor. To achieve substantial increase in the temporal resolution whilemaintaining low g-factors when high parallel imaging acceleration factors are used, the combination of segmented 3D EPI using 2D controlled aliasing with generalized autocalibrating partially parallel acquisitions (GRAPPA) was implemented in the next approach termed 3D-EPI-CAIPI. FunctionalMRI data with whole-brain coverage, a voxel size of 2 mm isotropic and a temporal resolution of 371 ms was acquired with acceptable image quality. 10-fold parallel imaging accelerated 3D-EPI-CAIPI data was shown to lower g-factor losses by as much as 10% with respect to segmented 3D EPI at 7 Tesla. Additional resting state networks were detected using 3D-EPI-CAIPI compared to a comparable standard 2D EPI acquisition. This was attributed to the improved statistics due to an increased number of volumes acquired in a given duration and because of the improved characterization of physiological signal fluctuations. Functional MRI with 400 ms temporal resolution allowed the detection of time-to-peak variations in temporal, occipital and frontal cortices haemodynamic responses due to multisensory facilitation of the order of ~200 ms. To conclude, this thesis introduces several novel techniques to increase temporal resolution of fMRI. Besides building theoretical foundations for these techniques, their applications for studying human brain functional connectivity, event-related brain activation and the ability to characterize physiological signal fluctuations at ultra-high field strength (7 Tesla) are evaluated.

EPFL2014

Multicontrast MRI Quantification of Focal Inflammation and Degeneration in Multiple Sclerosis

Guillaume Bonnier, Cristina Granziera, Ying-Chia Lin, Gloria Menegaz, Djalel Eddine Meskaldji, Alexis Roche, David Paul Roger Romascano, Jean-Philippe Thiran

Introduction. Local microstructural pathology in multiple sclerosis patients might influence their clinical performance. This study applied multicontrast MRI to quantify inflammation and neurodegeneration in MS lesions. We explored the impact of MRI-based lesion pathology in cognition and disability. Methods. 36 relapsing-remitting MS subjects and 18 healthy controls underwent neurological, cognitive, behavioural examinations and 3 T MRI including (i) fluid attenuated inversion recovery, double inversion recovery, and magnetization-prepared gradient echo for lesion count; (ii) T1, T2, and T2(*) relaxometry and magnetisation transfer imaging for lesion tissue characterization. Lesions were classified according to the extent of inflammation/neurodegeneration. A generalized linear model assessed the contribution of lesion groups to clinical performances. Results. Four lesion groups were identified and characterized by (1) absence of significant alterations, (2) prevalent inflammation, (3) concomitant inflammation and microdegeneration, and (4) prevalent tissue loss. Groups 1, 3, 4 correlated with general disability (Adj-R (2) = 0.6; P = 0.0005), executive function (Adj-R (2) = 0.5; P = 0.004), verbal memory (Adj-R (2) = 0.4; P = 0.02), and attention (Adj-R (2) = 0.5; P = 0.002). Conclusion. Multicontrast MRI provides a new approach to infer in vivo histopathology of plaques. Our results support evidence that neurodegeneration is the major determinant of patients' disability and cognitive dysfunction.

Hindawi Publishing Corporation2015

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Although often ignored in fMRI studies, moment-to-moment variability of blood oxygenation level dependent (BOLD) signals reveals important information about brain function. Indeed, higher brain signal variability has been associated with better cognitive performance in young adults compared to children and elderly adults. Functional connectivity, a very, common approach in resting-state fMRI analysis, is scaled for variance. Thus, alterations might be confounded or driven by BOLD signal variance alterations. Chromosome 22q11.2 deletion syndrome (22q11.2DS) is a neurodevelopmental disorder that is associated with a vast cognitive and clinical phenotype. To date, several resting-state fMRI studies reported altered functional connectivity in 22q11.2DS, however BOLD signal variance has not yet been analyzed. Here, we employed PLS correlation analysis to reveal multivariate patterns of diagnosis-related alterations and age-relationship throughout the cortex of 50 patients between 9 and 25 years old and 50 healthy controls in the same age range. To address how functional connectivity in the default mode network is influenced by BOLD signal fluctuations, we conducted the same analysis on seed-to-voxel connectivity of the posterior cingulate cortex (PCC) and compared resulting brain patterns. BOLD signal variance was lower mainly in regions of the default mode network and in the dorsolateral prefrontal cortex, but higher in large parts of the temporal lobes. In those regions, BOLD signal variance was correlated with age in healthy controls, but not in patients, suggesting deviant developmental trajectories from child- to adulthood. Positive connectivity of the PCC within the default mode network as well as negative connectivity towards the frontoparietal network were weaker in patients with 22q11.2DS. We furthermore showed that lower functional connectivity of the PCC was not driven by higher BOLD signal variability. Our results confirm the strong implication of BOLD variance in aging and give an initial insight in its relationship with functional connectivity in the DMN.

Elsevier2017

EPFL2014

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Elsevier2017