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Stephan Eliez

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12 papers

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YNIMG Journal 2023 Journal Article

The coupling between the spatial and temporal scales of neural processes revealed by a joint time-vertex connectome spectral analysis

Joan Rué-Queralt
Valentina Mancini
Vincent Rochas
Caren Latrèche
Peter J. Uhlhaas
Christoph M. Michel
Gijs Plomp
Stephan Eliez

Brain oscillations are produced by the coordinated activity of large groups of neurons and different rhythms are thought to reflect different modes of information processing. These modes, in turn, are known to occur at different spatial scales. Nevertheless, how these rhythms support different spatial modes of information processing at the brain scale is not yet fully understood. Here we use "Joint Time-Vertex Spectral Analysis" to characterize the joint spectral content of brain activity both in time (temporal frequencies) and in space over the connectivity graph (spatial connectome harmonics). This method allows us to characterize the relationship between spatially localized or distributed neural processes on one side and their respective temporal frequency bands in source-reconstructed M/EEG signals. We explore this approach on two different datasets, an auditory steady-state response (ASSR) and a visual grating task. Our results suggest that different information processing mechanisms are carried out at different frequency bands: while spatially distributed activity (which may also be interpreted as integration) specifically occurs at low temporal frequencies (alpha and theta) and low graph spatial frequencies, localized electrical activity (i.e., segregation) is observed at high temporal frequencies (high and low gamma) over restricted high spatial graph frequencies. Crucially, the estimated contribution of the distributed and localized neural activity predicts performance in a behavioral task, demonstrating the neurophysiological relevance of the joint time-vertex spectral representation.

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YNICL Journal 2022 Journal Article

Neural substrates of psychosis revealed by altered dependencies between brain activity and white-matter architecture in individuals with 22q11 deletion syndrome

Karin Bortolin
Farnaz Delavari
Maria Giulia Preti
Corrado Sandini
Valentina Mancini
Emeline Mullier
Dimitri Van De Ville
Stephan Eliez

BACKGROUND: Dysconnectivity has been consistently proposed as a major key mechanism in psychosis. Indeed, disruptions in large-scale structural and functional brain networks have been associated with psychotic symptoms. However, brain activity is largely constrained by underlying white matter pathways and the study of function-structure dependency, compared to conventional unimodal analysis, allows a biologically relevant assessment of neural mechanisms. The 22q11.2 deletion syndrome (22q11DS) constitutes a remarkable opportunity to study the pathophysiological processes of psychosis. METHODS: 58 healthy controls and 57 deletion carriers, aged from 16 to 32 years old,underwent resting-state functional and diffusion-weighted magnetic resonance imaging. Deletion carriers were additionally fully assessed for psychotic symptoms. Firstly, we used a graph signal processing method to combine brain activity and structural connectivity measures to obtain regional structural decoupling indexes (SDIs). We use SDI to assess the differences of functional structural dependency (FSD) across the groups. Subsequently we investigated how alterations in FSDs are associated with the severity of positive psychotic symptoms in participants with 22q11DS. RESULTS: In line with previous findings, participants in both groups showed a spatial gradient of FSD ranging from sensory-motor regions (stronger FSD) to regions involved in higher-order function (weaker FSD). Compared to controls, in participants with 22q11DS, and further in deletion carriers with more severe positive psychotic symptoms, the functional activity was more strongly dependent on the structure in parahippocampal gyrus and subcortical dopaminergic regions, while it was less dependent within the cingulate cortex. This analysis revealed group differences not otherwise detected when assessing the structural and functional nodal measures separately. CONCLUSIONS: Our findings point toward a disrupted modulation of functional activity on the underlying structure, which was further associated to psychopathology for candidate critical regions in 22q11DS. This study provides the first evidence for the clinical relevance of function-structure dependency and its contribution to the emergence of psychosis.

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YNICL Journal 2018 Journal Article

Visual processing deficits in 22q11.2 Deletion Syndrome

Marjan Biria
Miralena I. Tomescu
Anna Custo
Lucia M. Cantonas
Kun-Wei Song
Maude Schneider
Micah M. Murray
Stephan Eliez

Carriers of the rare 22q11.2 microdeletion present with a high percentage of positive and negative symptoms and a high genetic risk for schizophrenia. Visual processing impairments have been characterized in schizophrenia, but less so in 22q11.2 Deletion Syndrome (DS). Here, we focus on visual processing using high-density EEG and source imaging in 22q11.2DS participants (N = 25) and healthy controls (N = 26) with an illusory contour discrimination task. Significant differences between groups emerged at early and late stages of visual processing. In 22q11.2DS, we first observed reduced amplitudes over occipital channels and reduced source activations within dorsal and ventral visual stream areas during the P1 (100-125 ms) and within ventral visual cortex during the N1 (150-170 ms) visual evoked components. During a later window implicated in visual completion (240-285 ms), we observed an increase in global amplitudes in 22q11.2DS. The increased surface amplitudes for illusory contours at this window were inversely correlated with positive subscales of prodromal symptoms in 22q11.2DS. The reduced activity of ventral and dorsal visual areas during early stages points to an impairment in visual processing seen both in schizophrenia and 22q11.2DS. During intervals related to perceptual closure, the inverse correlation of high amplitudes with positive symptoms suggests that participants with 22q11.2DS who show an increased brain response to illusory contours during the relevant window for contour processing have less psychotic symptoms and might thus be at a reduced prodromal risk for schizophrenia.

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YNICL Journal 2017 Journal Article

Altered structural network architecture is predictive of the presence of psychotic symptoms in patients with 22q11.2 deletion syndrome

Maria C. Padula
Elisa Scariati
Marie Schaer
Corrado Sandini
Marie Christine Ottet
Maude Schneider
Dimitri Van De Ville
Stephan Eliez

22q11. 2 deletion syndrome (22q11DS) represents a homogeneous model of schizophrenia particularly suitable for the search of neural biomarkers of psychosis. Impairments in structural connectivity related to the presence of psychotic symptoms have been reported in patients with 22q11DS. However, the relationships between connectivity changes in patients with different symptomatic profiles are still largely unknown and warrant further investigations. In this study, we used structural connectivity to discriminate patients with 22q11DS with (N =31) and without (N =31) attenuated positive psychotic symptoms. Different structural connectivity measures were used, including the number of streamlines connecting pairs of brain regions, graph theoretical measures, and diffusion measures. We used univariate group comparisons as well as predictive multivariate approaches. The univariate comparison of connectivity measures between patients with or without attenuated positive psychotic symptoms did not give significant results. However, the multivariate prediction revealed that altered structural network architecture discriminates patient subtypes (accuracy=67. 7%). Among the regions contributing to the classification we found the anterior cingulate cortex, which is known to be associated to the presence of psychotic symptoms in patients with 22q11DS. Furthermore, a significant discrimination (accuracy=64%) was obtained with fractional anisotropy and radial diffusivity in the left inferior longitudinal fasciculus and the right cingulate gyrus. Our results point to alterations in structural network architecture and white matter microstructure in patients with 22q11DS with attenuated positive symptoms, mainly involving connections of the limbic system. These alterations may therefore represent a potential biomarker for an increased risk of psychosis that should be further tested in longitudinal studies.

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YNIMG Journal 2017 Journal Article

Disentangling resting-state BOLD variability and PCC functional connectivity in 22q11.2 deletion syndrome

Daniela Zöller
Marie Schaer
Elisa Scariati
Maria Carmela Padula
Stephan Eliez
Dimitri Van De Ville

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.

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YNICL Journal 2016 Journal Article

An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome

František Váša
Alessandra Griffa
Elisa Scariati
Marie Schaer
Sébastien Urben
Stephan Eliez
Patric Hagmann

Chromosome 22q11.2 deletion syndrome (22q11DS) is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes), we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure) as the affected core (A-core) of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs - chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, "de-centralizing" the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30-40% of 22q11DS patients develop.

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YNICL Journal 2013 Journal Article

Early adversity and combat exposure interact to influence anterior cingulate cortex volume in combat veterans

Steven H. Woodward
Janice R. Kuo
Marie Schaer
Danny G. Kaloupek
Stephan Eliez

OBJECTIVE: Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach. METHOD: Anterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis. RESULTS: As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes. CONCLUSIONS: In the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma.

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YNIMG Journal 2013 Journal Article

Sex differences in thickness, and folding developments throughout the cortex

A. Kadir Mutlu
Maude Schneider
Martin Debbané
Deborah Badoud
Stephan Eliez
Marie Schaer

While significant differences in male and female brain structures have commonly been reported, only a few studies have focused on the sex differences in the way the cortex matures over time. Here, we investigated cortical thickness maturation between the age of 6 to 30years, using 209 longitudinally-acquired brain MRI scans. Significant sex differences in the trajectories of cortical thickness change with age were evidenced using non-linear mixed effects models. Similar statistical analyses were computed to quantify the differences between cortical gyrification changes with age in males and females. During adolescence, we observed a statistically significant higher rate of cortical thinning in females compared to males in the right temporal regions, the left temporoparietal junction and the left orbitofrontal cortex. This finding is interpreted as a faster maturation of the social brain areas in females. Concomitantly, statistically significant sex differences in cortical folding changes with age were observed only in one cluster of the right prefrontal regions, suggesting that the mechanisms underlying cortical thickness and gyrification changes with age are quite distinct. Sexual dimorphism in the developmental course of the cortical maturation may be associated with the different age of onset and clinical presentation of many psychiatric disorders between males and females.

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YNIMG Journal 2011 Journal Article

Neural correlates of reality monitoring during adolescence

AnnaLaura Lagioia
Stephan Eliez
Maude Schneider
Jon S. Simons
Martial Van der Linden
Martin Debbané

Background Reality monitoring processes serve the critical function of discriminating between externally derived information and self-generated information. Several reality monitoring studies with healthy adult participants have identified the anterior prefrontal cortex (PFC) as consistently engaged during the recollection of self-generated contextual cues. Furthermore, reduced activity of medial PFC has been linked with schizotypal trait expression of delusion and hallucination-like symptoms in healthy adults undergoing fMRI reality-monitoring tasks. The present study seeks to examine the cerebral underpinnings of reality monitoring during adolescence, a developmental stage where the expression of schizotypal traits may increase risk for psychosis. Method A group of 33 adolescents, assessed using the Schizotypal Personality Scale (SPQ), underwent fMRI while performing a reality monitoring task. After an encoding session where the subject or the experimenter read out a series of complete or incomplete word pairs, subjects were presented with the first word of studied word pairs and asked whether the corresponding word had been: (1) perceived or produced (context monitoring), or (2) read by the subject or by the experimenter (origin monitoring). Results Analyses revealed a common set of activated brain areas during both context and origin monitoring conditions. When compared to context monitoring, origin monitoring was associated with greater activation in anterior PFC within Brodmann area 10 (BA 10). Correlation analyses revealed that reduced signal change in BA 10 during origin monitoring was associated with greater schizotypal trait expression. Conclusion Much like adults performing a similar reality monitoring task, adolescents exhibit a common pattern of brain activity during origin and context monitoring, with functional specialization within the prefrontal cortex involving preferential activation of BA 10 during origin monitoring. Greater schizotypal trait expression appears to be significantly associated to reduced BA 10 activity during origin monitoring trials. Results are discussed in relation to cortical specialization within the PFC and trait expression during adolescence.

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YNIMG Journal 2003 Journal Article

Effect of head orientation on gaze processing in fusiform gyrus and superior temporal sulcus

Natalie M Pageler
Vinod Menon
Noah M Merin
Stephan Eliez
Wendy E Brown
Allan L Reiss

We used functional MRI with an event-related design to dissociate the brain activation in the fusiform gyrus (FG) and posterior superior temporal sulcus (STS) for multiple face and gaze orientations. The event-related design allowed for concurrent behavioral analysis, which revealed a significant effect of both head and gaze orientation on the speed of gaze processing, with the face and gaze forward condition showing the fastest reaction times. In conjunction with this behavioral finding, the FG responded with the greatest activation to face and gaze forward, perhaps reflecting the unambiguous social salience of congruent face and gaze directed toward the viewer. Random effects analysis showed greater activation in both the FG and posterior STS when the subjects viewed a direct face compared to an angled face, regardless of gaze direction. Additionally, the FG showed greater activation for forward gaze compared to angled gaze, but only when the face was forward. Together, these findings suggest that head orientation has a significant effect on gaze processing and these effects are manifest not only in the STS, but also the FG.

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YNIMG Journal 2003 Journal Article

Interactive specification of regions of interest on brain surfaces

Smadar Shiffman
Yi-Ren Ng
Thomas J Brosnan
Stephan Eliez
Jonathan M Links
Uma V Kelkar
Allan L Reiss

We describe Surface Editor—a tool for interactive specification of regions of interest (ROIs) on brain surfaces. The tool allows users to define subsurfaces by tracing around areas within a triangle-mesh brain surface. The input to the program is a triangle-mesh representation of a brain volume and a set of user-defined input points on the mesh. The program connects each pair of successive input points with a polyline that results from the intersection of the mesh with a plane that is approximately normal to the mesh. The polyline comprises coplanar line segments. The boundary of an ROI is a connected set of polylines that intersects triangle edges to form a continuous path. To validate Surface Editor we demonstrated that the program could be used to interactively delineate gyri on brain surfaces, and we showed that paths that the program generated were comparable to paths that a user generated and to shortest paths.

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YNIMG Journal 2003 Journal Article

Neural Correlates of Auditory Perception in Williams Syndrome: An fMRI Study

Daniel J. Levitin
Vinod Menon
J.Eric Schmitt
Stephan Eliez
Christopher D. White
Gary H. Glover
Jay Kadis
Julie R. Korenberg

Williams syndrome (WS), a neurogenetic developmental disorder, is characterized by a rare fractionation of higher cortical functioning: selective preservation of certain complex faculties (language, music, face processing, and sociability) in contrast to marked and severe deficits in nearly every other cognitive domain (reasoning, spatial ability, motor coordination, arithmetic, problem solving). WS people are also known to suffer from hyperacusis and to experience heightened emotional reactions to music and certain classes of noise. We used functional magnetic resonance imaging to examine the neural basis of auditory processing of music and noise in WS patients and age-matched controls and found strikingly different patterns of neural organization between the groups. Those regions supporting music and noise processing in normal subjects were found not to be consistently activated in the WS participants (e. g. , superior temporal and middle temporal gyri). Instead, the WS participants showed significantly reduced activation in the temporal lobes coupled with significantly greater activation in the right amygdala. In addition, WS participants (but not controls) showed a widely distributed network of activation in cortical and subcortical structures, including the brain stem, during music processing. Taken together with previous ERP and cytoarchitectonic studies, this first published report of WS using fMRI provides additional evidence of a different neurofunctional organization in WS people than normal people, which may help to explain their atypical reactions to sound. These results constitute an important first step in drawing out the links between genes, brain, cognition, and behavior in Williams syndrome.

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