Biology subjects

Eliez, S.

Publications and source records attributed to Eliez, S..

10 recordsLinked to original sources

bioRxiv2026

Claustrum Morphometry Reveals Spatially Heterogeneous Alterations in 22q11DS

The human claustrum is a small, irregular, and complexly positioned structure, yet it carries long range projections to most cortical regions responsible for executive functioning. Prior structural MRI research has largely relied on global volume as the metric of its morphology. Such measures may obscure regionally specific morphological changes relevant to developmental and pathological variation. We therefore addressed this limitation by applying longitudinal surface-based morphometry to 874 scans from 440 individuals aged 5-35 years, comparing typical development with 22q11.2 deletion syndrome (22q11DS), a genetic condition characterized by brain dysmaturation, and assessing associations with working memory performance. Our data show a significant age-related volumetric decline that is reduced in 22q11DS left claustra, while surface deformation and thickness analyses revealed spatial patterns unique to hemisphere, group, and developmental age. In controls, the claustrum surface deformed with age in clustered zones along a dorsoventral gradient, and the dorsal-anterior zone thinned across development while the ventral zone thickened. 22q11DS claustra showed less age-related deformation than controls, whose claustrum surface changes associated with verbal working memory. This structural correlate was statistically equivalent to zero in carriers, consistent with a disrupted claustral development to the working memory vulnerability of the syndrome. These findings show the value of surface-based morphometry over volume alone, highlight dysmaturation and regionally organized claustrum shape variation, and suggest that disrupted structural organization is accompanied by a weaker claustrum-working memory association.

neuroscience↗

bioRxiv2026

MRSIPrep: A Standardized Post-Quantification Framework for Preprocessing Whole-Brain Magnetic Resonance Spectroscopic Imaging

Magnetic resonance spectroscopic imaging (MRSI) enables non-invasive mapping of neu-rometabolites levels across the human brain. Although spectral fitting and metabolite quan-tification are increasingly supported by mature software tools, the downstream processing of quantified metabolite maps remains heterogeneous across laboratories. Here, we introduce MRSIPrep, an open-source, modular, and reproducible post-quantification framework for whole-brain MRSI. MRSIPrep standardizes quality control, tissue correction, spatial nor- malization, atlas projection, and derivative generation from quantified metabolite maps and associated quality metrics. The framework produces voxelwise, regional, and connectomics-ready outputs together with automated quality-control reports. We describe the architecture of MRSIPrep and demonstrate its utility for reproducible MRSI analysis across datasets,acquisition protocols, and downstream applications.

neuroscience↗

bioRxiv2026

Sex differences in brain metabolism assessed with whole-brain magnetic resonance spectroscopic imaging

Sex differences in brain disorders span age at onset, symptom profiles, disease course and treatment response, and may partly reflect underlying differences in cellular metabolism. Indeed, in vivo evidence of sex-related neurometabolic variation remains sparse, with heterogenous and conflicting findings. Using fast high-resolution whole-brain three-dimensional magnetic resonance spectroscopic imaging, we mapped five brain metabolites in three independent cohorts of healthy participants (total n = 114). In a discovery sample of adolescents scanned at 3 Tesla (3T) (n = 61), males showed higher total N-acetylaspartate (tNAA) across widespread gray matter regions. Regional analyses further revealed opposing sex patterns with a complementary higher total creatine (tCr) observed in females, motivating examination of their ratio as an integrative metabolic index. The tNAA/tCr ratio was consistently higher in males in the discovery sample and this finding was replicated across two independent young-adult samples (3T, n = 26; 7T, n = 27), with a widespread gray and white matter distribution. This tNAA/tCr ratio may link neuronal mitochondrial metabolism with cellular energy buffering, positioning it as a potential index of bioenergetic balance relevant for conditions showing both sex differences and altered neurometabolism, notably multiple sclerosis, Alzheimer disease, and psychosis. Together, these findings reveal a reproducible, distributed metabolic sexual dimorphism in the human brain, and underscore the importance of accounting for sex-specific neurometabolic profiles in studies of brain health and disease.

neuroscience↗

bioRxiv2025

Aberrant cerebrovascular reactivity presents as an early biomarker of psychosis susceptibility in patients with 22q11.2DS

The brains ability to regulate blood flow is fundamental to both its function and development. In the context of neurodevelopmental disorders such as schizophrenia, understanding the complex interactions between cerebrovascular health and brain function is crucial for unraveling the pathophysiology of psychosis. This study investigates the developmental trajectory of cerebrovascular reactivity (CVR) in 22q11 deletion syndrome (22q11.2DS) compared to healthy controls, and its association with psychosis susceptibility. Using a longitudinal data-set of resting-state fMRI, we mapped voxel-level CVR across development. We found significant and early CVR impairments in 22q11.2DS, and in particular in those who later developed positive psychotic symptoms (PPS+). These impairments were evident within the anterior cingulate cortex, frontal lobes, and globi pallidi (GB). We propose that the pattern of CVR reduction presenting early during childhood is possibly linked to blood brain barrier impairment. A decrease in CVR during childhood and within the frontal regions and GB was predictive of subsequent development of positive psychotic symptoms (PPS), which often occurs during adolescence in 22q11.2DS patients. These findings suggest that cerebrovascular health is critical for normal brain development, particularly in regions like the striatum, which are vulnerable to vascular damage due to their anatomical features. These results underline the potential of CVR as an early biomarker for psychosis vulnerability, emphasizing the need for targeted interventions to mitigate neurodevelopmental disruptions of cerebrovascular health in 22q11.2DS.

neuroscience↗

bioRxiv2023

Thalamic contributions to psychosis susceptibility: Evidence from co-activation patterns accounting for intra-seed spatial variability (μCAPs)

The temporal variability of the thalamus in functional networks may provide valuable insights into the pathophysiology of schizophrenia. To address the complexity of the role of the thalamic nuclei in psychosis, we introduced micro-co-activation patterns (CAPs) by employing this method on the human genetic model of schizophrenia 22q11.2 deletion syndrome (22q11.2DS). Participants underwent resting-state functional MRI and a data-driven iterative process resulting in the identification of six whole-brain CAPs with specific activity patterns within the thalamus. Unlike conventional methods, CAPs extract dynamic spatial patterns that reveal partially overlapping and non-mutually exclusive functional subparts. Thus, the CAPs method detects finer foci of activity within the initial seed region, retaining valuable and clinically relevant temporal and spatial information. We found that a CAP showing co-activation of the mediodorsal thalamus with brain-wide cortical regions was significantly less frequent in patients with 22q11.2DS, and its occurrence negatively correlated with the severity of positive psychotic symptoms. Additionally, the activity within the auditory-visual cortex and their respective geniculate nuclei were expressed in two different CAPs. One of these auditory-visual CAPs co-activated with salience areas, while the other co-activated with the default mode network (DMN). A significant shift of occurrence from the salience+visuo-auditory-thalamus to the DMN+visuo-auditory-thalamus CAP was observed in patients with 22q11.2DS. Thus, our findings support existing research on the gatekeeping role of the thalamus for sensory information in the pathophysiology of psychosis and revisit the evidence of geniculate nuclei hyperconnectivity with the audio-visual cortex in 22q11.2DS in the context of dynamic functional connectivity as specific hyper-occurrence of these circuits with the task negative brain networks.

neuroscience↗

bioRxiv2022

Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS and sporadic congenital heart disease

BackgroundCongenital heart disease (CHD) affecting the conotruncal region of the heart, occur in half of patients with 22q11.2 deletion syndrome. This syndrome is a rare disorder with relative genetic homogeneity that can facilitate identification of genetic modifiers. Haploinsufficiency of TBX1, mapped to the 22q11.2 region, encoding a T-box transcription factor, is one of the main genes for the etiology of the syndrome. We suggest that genetic modifiers of CHD in patients with 22q11.2 deletion syndrome may be in the TBX1 gene network. MethodsTo identify genetic modifiers of 22q11.2 deletion syndrome, we analyzed whole genome sequence of subjects with 22q11.2DS, of which 456 were cases with conotruncal heart defects and 537 were controls with normal cardiac structures. We retained the most damaging rare coding variants and examined 19 functional gene sets for association that were weighted upon expression of genes in cardiac progenitor cells in mouse embryos identified by RNA-sequencing. ResultsWe identified rare damaging coding variants in chromatin regulatory genes as modifiers of conotruncal heart defects in 22q11.2DS. Chromatin genes with recurrent damaging variants include EP400, KAT6A, KMT2C, KMT2D, NSD1, CHD7 and PHF21A. In total, we identified 37 chromatin regulatory genes, that may increase risk for conotruncal heart defects in 8.5% of 22q11.2 deletion syndrome cases. Many of these genes were identified as risk factors for sporadic CHD in the general population increasing the likelihood that these genes are medically important contributors for CHD. These genes are co-expressed in cardiac progenitor cells with TBX1, suggesting that they may be in the same genetic network. Some of the genes identified, such as KAT6A, KMT2C, CHD7 and EZH2, have been previously shown to genetically interact with TBX1 in mouse models, providing mechanistic validation of these genes found. ConclusionsOur findings indicate that disturbance of chromatin regulatory genes impact a TBX1 gene network serving as genetic modifiers of 22q11.2 deletion syndrome. Since some of these chromatin regulatory genes were found in individuals with sporadic CHD, we suggest that there are shared mechanisms involving the TBX1 gene network in the etiology of CHD.

genetics↗

bioRxiv2022

Neural integration and segregation revealed by a joint time-vertex connectome spectral analysis

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 modes of information processing at the brain scale is not yet fully understood. Here we present "Joint Time-Vertex Connectome Spectral Analysis", a framework for characterizing the spectral content of brain activity both in time (temporal frequencies) and in space (spatial connectome harmonics). This method allows us to estimate the contribution of integration (global communication) and segregation (functional specialization) mechanisms at different temporal frequency bands in source-reconstructed M/EEG signals, thus providing a better understanding of the complex interplay between different information processing modes. We validated our method 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 channels: while integration seems to be a specific mechanism occurring at low temporal frequencies (alpha and theta), segregation is only observed at higher temporal frequencies (high and low gamma). Crucially, the estimated contribution of the integration and segregation mechanisms predicts performance in a behavioral task, demonstrating the neurophysiological relevance of this new framework.

neuroscience↗

bioRxiv2019

Structural control energy of resting-state functional brain states reveals inefficient brain dynamics in psychosis vulnerability.

How the brains white-matter anatomy constrains brain activity is an open question that might give insights into the mechanisms that underlie mental disorders such as schizophrenia. Chromosome 22q11.2 deletion syndrome (22q11DS) is a neurodevelopmental disorder with an extremely high risk for psychosis providing a test case to study developmental aspects of schizophrenia. In this study, we used principles from network control theory to probe the implications of aberrant structural connectivity for the brains functional dynamics in 22q11DS. We retrieved brain states from resting-state functional magnetic resonance images of 78 patients with 22q11DS and 85 healthy controls. Then, we compared them in terms of persistence control energy; i.e., the control energy that would be required to persist in each of these states based on individual structural connectivity and a dynamic model. Persistence control energy was altered in a broad pattern of brain states including both energetically more demanding and less demanding brain states in 22q11DS. Further, we found a negative relationship between persistence control energy and resting-state activation time, which suggests that the brain reduces energy by spending less time in energetically demanding brain states. In patients with 22q11DS, this behavior was less pronounced, suggesting a dynamic inefficiency of brain function in the disease. In summary, our results provide initial insights into the dynamic implications of altered structural connectivity in 22q11DS, which might improve our understanding of the mechanisms underlying the disease.

neuroscience↗

bioRxiv2019

Large-scale brain network dynamics provide a measure of psychosis and anxiety in 22q11.2 deletion syndrome.

Prodromal positive psychotic symptoms and anxiety are two strong risk factors for schizophrenia in 22q11.2 deletion syndrome (22q11DS). The analysis of large-scale brain network dynamics during rest is promising to investigate aberrant brain function and identify potentially more reliable biomarkers. We retrieved and examined dynamics of large-scale functional brain networks using innovation-driven co-activation patterns (iCAPs) and probed into functional signatures of prodromal psychotic symptoms and anxiety. Patients with 22q11DS had shorter activation in cognitive brain networks and longer activation in emotion processing networks. Functional signatures of prodromal psychotic symptoms confirmed an implication of cingulo-prefrontal salience network activation duration and coupling. Functional signatures of anxiety un-covered an implication of amygdala activation and coupling, indicating differential roles of dorsal and ventral sub-divisions of anterior cingulate and medial prefrontal cortices. These results confirm that the dynamic nature of brain network activation contains essential function to develop clinically relevant imaging markers of psychosis vulnerability.

neuroscience↗

bioRxiv2017

Early alterations of social brain networks in young children with autism

Social impairments are a hallmark of Autism Spectrum Disorders (ASD), but empirical evidence for early brain network alterations in response to social stimuli is scant in ASD. Here, we recorded the gaze patterns and brain activity of toddlers and preschoolers with ASD and their typically developing (TD) peers while they explored dynamic social scenes. Source-space directed functional connectivity analyses revealed the presence of network alterations in the theta frequency band, manifesting as increased driving (hyper-activity) and stronger connections (hyper-connectivity) from key nodes of the social brain associated with autism. Further analyses of brain-behavioural relationships within the ASD group suggested that compensatory mechanisms from dorsomedial frontal, inferior temporal and insular cortical regions were associated with lower clinical impairment and less atypical gaze patterns. Our results provide strong evidence that directed functional connectivity alterations of social brain networks is a core component of atypical brain development at early stages of ASD.

neuroscience↗