Elisabeth Soulier

Decreased basal fMRI functional connectivity in epileptogenic networks and contralateral compensatory mechanisms.

A better understanding of interstructure relationship sustaining drug‐resistant epileptogenic networks is crucial for surgical perspective and to better understand the consequences of epileptic processes on cognitive functions. We used resting‐state fMRI to study basal functional connectivity within temporal lobes in medial temporal lobe epilepsy (MTLE) during interictal period. Two hundred consecutive single‐shot GE‐EPI acquisitions were acquired in 37 right‐handed subjects (26 controls, eight patients presenting with left and three patients with right MTLE). For each hemisphere, normalized correlation coefficients were computed between pairs of time‐course signals extracted from five regions involved in MTLE epileptogenic networks (Brodmann area 38, amygdala, entorhinal cortex (EC), anterior hippocampus (AntHip), and posterior hippocampus (PostHip)). In controls, an asymmetry was present with a global higher connectivity in the left temporal lobe. Relative to controls, the left MTLE group showed disruption of the left EC‐AntHip link, and a trend of decreased connectivity of the left AntHip‐PostHip link. In contrast, a trend of increased connectivity of the right AntHip‐PostHip link was observed and was positively correlated to memory performance. At the individual level, seven out of the eight left MTLE patients showed decreased or disrupted functional connectivity. In this group, four patients with left TLE showed increased basal functional connectivity restricted to the right temporal lobe spared by seizures onset. A reverse pattern was observed at the individual level for patients with right TLE. This is the first demonstration of decreased basal functional connectivity within epileptogenic networks with concomitant contralateral increased connectivity possibly reflecting compensatory mechanisms. Hum Brain Mapp 2009.

Magnetic resonance study of the influence of tissue damage and cortical reorganization on PASAT performance at the earliest stage of multiple sclerosis.

We sought to determine the influence of tissue damage and the potential impact of cortical reorganization on the performance to the Paced Auditory Serial Addition Test (PASAT) in patients at the earliest stage of multiple sclerosis (MS). Magnetization transfer ratio (MTR) imaging and functional magnetic resonance imaging (fMRI) experiments using PASAT as paradigm were carried out in 18 patients with clinically isolated syndrome suggestive of MS (CISSMS) compared to 18 controls. MTR histogram analyses showed structural abnormalities in patients involving the normal‐appearing white matter (NAWM) but also the gray matter (GM). Mean PASAT scores were significantly lower in the group of patients taken as a whole, and were correlated with the mean NAWM MTR value. No correlation was observed between PASAT scores and GM MTR. However, in the subgroup of patients with normal PASAT performance (n = 9), fMRI showed larger activations in bilateral Brodmann area 45 (BA45) and right BA44 compared to that in controls (n = 18). In these areas with potentially compensatory reorganization, the whole group of patients (n = 18) showed significantly greater activation than controls (n = 18). Activation in the right BA45 was inversely correlated with the mean NAWM MTR and the peak position of GM MTR histograms of patients. This study indicates that even at the earliest stage of MS, cortical reorganization is present inside the executive system of working memory and could tend to limit the determinant functional impact of NAWM injury on the execution of the PASAT. Hum. Brain Mapping 24:216–228, 2005.

Structure of WM bundles constituting the working memory system in early multiple sclerosis: A quantitative DTI tractography study

Working memory impairment is frequently observed in patients with early multiple sclerosis (MS). MRI and functional MRI studies have shown that working memory impairment is mostly due to diffuse white matter (WM) damage affecting the connectivity between distant cortical areas. However, working memory deficits in early MS patients can be either completely or partly masked by compensatory functional plasticity. It seems likely that concomitantly with the WM bundle injury resulting from pathological processes, the functional plasticity present in early MS patients may be accompanied by reactive structural WM plasticity. This structural plasticity may effectively compensate for connectivity disturbances and/or contribute to functional brain reorganization. The diffusion characteristics of WM bundles involved in working memory were assessed here by performing quantitative diffusion tensor imaging (DTI) tractography on 24 patients with early relapsing-remitting MS and 15 healthy control subjects. The DTI tractography findings showed that WM connections constituting the executive system of working memory were structurally impaired (the fractional anisotropy was lower than normal and the mean diffusivity, higher than normal). A significantly larger number of connections between the left and right thalami was concurrently observed in the MS patients than in the control subjects, which suggests that the WM is endowed with reactive structural plasticity.

Assessing brain connectivity at rest is clinically relevant in early multiple sclerosis

Objective: The present study aims to determine the clinical counterpart of brain resting-state networks reorganization recently evidenced in early multiple sclerosis. Methods: Thirteen patients with early relapsing–remitting multiple sclerosis and 14 matched healthy controls were included in a resting state functional MRI study performed at 3 T. Data were analyzed using group spatial Independent Component Analysis using concatenation approach (FSL 4.1.3) and double regression analyses (SPM5) to extract local and global levels of connectivity inside various resting state networks (RSNs). Differences in global levels of connectivity of each network between patients and controls were assessed using Mann–Whitney U-test. In patients, relationship between clinical data (Expanded Disability Status Scale and Multiple Sclerosis Functional Composite Score – MSFC) and global RSN connectivity were assessed using Spearman rank correlation. Results: Independent component analysis provided eight consistent neuronal networks involved in motor, sensory and cognitive processes. For seven RSNs, the global level of connectivity was significantly increased in patients compared with controls. No significant decrease in RSN connectivity was found in early multiple sclerosis patients. MSFC values were negatively correlated with increased RSN connectivity within the dorsal frontoparietal network (r = −0.811, p = 0.001), the right ventral frontoparietal network (r = − 0.587, p = 0.045) and the prefronto-insular network (r = −0.615, p = 0.033). Conclusions: This study demonstrates that resting state networks reorganization is strongly associated with disability in early multiple sclerosis. These findings suggest that resting state functional MRI may represent a promising surrogate marker of disease burden.

Voxel‐based analysis of MTR images: A method to locate gray matter abnormalities in patients at the earliest stage of multiple sclerosis

To determine whether voxel‐based analysis of magnetization transfer ratio (MTR) maps can provide evidence of a coherent pattern of gray matter (GM) macroscopic and microscopic tissue damage in patients at the earliest stage of multiple sclerosis (MS).

Profile of memory impairment and gray matter loss in amnestic mild cognitive impairment

The present study assessed the patterns of cortical gray matter (GM) loss in patients with amnestic mild cognitive impairment (aMCI) with distinct profiles of memory impairment, i.e. aMCI patients failing on both recall and recognition memory vs. aMCI patients showing impaired recall but preserved recognition memory. This distinction is usually not taken into account in studies on aMCI and the aim of the present study was to assess whether this distinction is useful. Twenty-eight aMCI patients and 28 matched controls subjects were included. All aMCI patients failed a recall memory task (inclusion criteria). All underwent a visual recognition memory task (DMS48). However, 12 succeeded on this task while 16 failed. Relative gray matter (GM) loss was measured using voxel-based morphometry. When comparing aMCI patients to controls regardless of the profile of memory impairment, GM loss was found in temporal, parietal and frontal areas. However, in aMCI patients with preserved recognition (but impaired recall), GM loss was confined to frontal areas. This contrasted with GM loss in the right medial temporal lobe and bilateral temporo-parietal regions in aMCI patients with impaired recall and recognition memory, a pattern of GM loss usually described in early AD. We conclude that different profiles of memory impairment in aMCI patients are associated with distinct patterns of GM loss.

Basal functional connectivity within the anterior temporal network is associated with performance on declarative memory tasks

Spontaneous fluctuations in the blood oxygenation level-dependent (BOLD) signal, as measured by functional magnetic resonance imaging (fMRI) at rest, exhibit a temporally coherent activity thought to reflect functionally relevant networks. Antero-mesial temporal structures are the site of early pathological changes in Alzheimers disease and have been shown to be critical for declarative memory. Our study aimed at exploring the functional impact of basal connectivity of an anterior temporal network (ATN) on declarative memory. A heterogeneous group of subjects with varying performance on tasks assessing memory was therefore selected, including healthy subjects and patients with isolated memory complaint, amnestic Mild Cognitive Impairment (aMCI) and mild Alzheimers disease (AD). Using Independent Component Analysis on resting-state fMRI, we extracted a relevant anterior temporal network (ATN) composed of the perirhinal and entorhinal cortex, the hippocampal head, the amygdala and the lateral temporal cortex extending to the temporal pole. A default mode network and an executive-control network were also selected to serve as control networks. We first compared basal functional connectivity of the ATN between patients and control subjects. Relative to controls, patients exhibited significantly increased functional connectivity in the ATN during rest. Specifically, voxel-based analysis revealed an increase within the inferior and superior temporal gyrus and the uncus. In the patient group, positive correlations between averaged connectivity values of ATN and performance on anterograde and retrograde object-based memory tasks were observed, while no correlation was found with other evaluated cognitive measures. These correlations were specific to the ATN, as no correlation between performance on memory tasks and the other selected networks was found. Taken together, these findings provide evidence that basal connectivity inside the ATN network has a functional role in object-related, context-free memory. They also suggest that increased connectivity at rest within the ATN could reflect compensatory mechanisms that occur in response to early pathological insult.

Distribution of Brain Sodium Accumulation Correlates with Disability in Multiple Sclerosis: A Cross-sectional 23Na MR Imaging Study

PURPOSE To quantify brain sodium accumulations and characterize for the first time the spatial location of sodium abnormalities at different stages of relapsing-remitting (RR) multiple sclerosis (MS) by using sodium 23 ((23)Na) magnetic resonance (MR) imaging. MATERIALS AND METHODS This study was approved by the local committee on ethics, and written informed consent was obtained from all participants. Three-dimensional (23)Na MR imaging data were obtained with a 3.0-T unit in two groups of patients with RR MS-14 with early RR MS (disease duration <5 years) and 12 with advanced RR MS (disease duration >5 years)-and 15 control subjects. Quantitative assessment of total sodium concentration (TSC) levels within compartments (MS lesions, white matter [WM], and gray matter [GM]) as well as statistical mapping analyses of TSC abnormalities were performed. RESULTS TSC was increased inside demyelinating lesions in both groups of patients, whereas increased TSC was observed in normal-appearing WM and GM only in those with advanced RR MS. In patients, increased TSC inside GM was correlated with disability (as determined with the Expanded Disability Status Scale [EDSS] score; P = .046, corrected) and lesion load at T2-weighted imaging (P = .003, corrected) but not with disease duration (P = .089, corrected). Statistical mapping analysis showed confined TSC increases inside the brainstem, cerebellum, and temporal poles in early RR MS and widespread TSC increases that affected the entire brain in advanced RR MS. EDSS score correlated with TSC increases inside motor networks. CONCLUSION TSC accumulation dramatically increases in the advanced stage of RR MS, especially in the normal-appearing brain tissues, concomitant with disability. Brain sodium MR imaging may help monitor the occurrence of tissue injury and disability.

Onset and underpinnings of white matter atrophy at the very early stage of multiple sclerosis. A two-year longitudinal MRI/MRSI study of corpus callosum.

Backgrounds Atrophy of corpus callosum (CC), a white matter structure linking the two hemispheres, is commonly observed in multiple sclerosis (MS). However, the occurrence and processes leading to this alteration are not yet determined. Goal and methods To better characterize the onset and progression of CC atrophy from the early stage of MS, we performed a two-year follow-up magnetic resonance imaging/magnetic resonance spectroscopic imaging (MRI/MRSI) exploration of CC in 24 patients with clinically isolated syndrome. These patients were explored using the same protocol at month (M)6, M12 and M24. MRI/MRSI techniques were applied to measure CC volume, and relative concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr) and choline-containing compounds (Cho). A group of matched controls was also explored. Results Atrophy of CC, not present at baseline, was observed at M12 and progressed over the second year (M24). At baseline, a decrease in relative NAA level was observed in the anterior and posterior body of CC, with normalization during the follow-up period. In the anterior body, an increase in relative Cho level was observed, with normalization at M6. Normal relative Cr levels were observed at all time points in all sub-regions. The rate of CC atrophy was correlated with the change in the Expanded Disability Status Scale (EDSS) during the follow-up period. Conclusion These results suggest that CC atrophy appears over a period of one year after the first acute inflammatory episode, and that this atrophy is accompanied, especially in the anterior body of CC, by a normalization of the relative Cho levels, marker of acute inflammation, and NAA levels, marker of neuronal dysfunction and/or loss.

Structural and functional surrogates of cognitive impairment at the very early stage of multiple sclerosis

Following our previous reports based on parametric MRI methods (T(2)-weighted MRI, statistical mapping analysis of magnetization transfer ratio images and functional MRI) applied to a population of 18 patients with clinically isolated syndrome suggestive of multiple sclerosis, we have reviewed the possible structural and functional surrogates of MS that could explain the subtle cognitive impairment related to attention and working memory deficits evaluated with paced auditory serial addition test (PASAT). We propose that the brain substrates underlying cognitive impairment observed at the very early stage of MS are multifactorial. Several components could influence PASAT performances in patients: i) the extent of diffuse white matter damage, ii) the location of visible and non visible lesions, iii) the connectivity efficiency between distant brain functional areas involved in working memory processes and iv) the cortical reorganization. Nevertheless, individually, each of these parameters may have few influences on PASAT performance in patients. Using a multiregression model built with independent MR parameters, a very good evaluation of PASAT scores has been obtained in this limited number of patients explaining 90% of the variance. In conclusion, the different aspects of tissue and functional pathological brain underpinnings must be accounted to monitor accurately new therapeutic strategies for the treatment of early cognitive deficits related to MS.