publications

2021

1. Attention to Face as a Predictor of Developmental Change and Treatment Outcome in Young Children with Autism Spectrum Disorder

   Latrèche, K., Kojovic, N., Franchini, M., and Schaer, M.

   Biomedicines 2021

   Abstract URL PDF

   The beneficial effect of early intervention is well described for children with autism spectrum disorder (ASD). Response to early intervention is, however, highly heterogeneous in affected children, and there is currently only scarce information about predictors of response to intervention. Based on the hypothesis that impaired social orienting hinders the subsequent development of social communication and interactions in children with ASD, we sought to examine whether the level of social orienting modulates treatment outcome in young children with ASD. We used eye-tracking technology to measure social orienting in a group of 111 preschoolers, comprising 95 young children with ASD and 16 children with typical development, as they watched a 29 s video of a woman engaging in child-directed speech. In line with previous studies, we report that attention to face is robustly correlated with autistic symptoms and cognitive and adaptive skills at baseline. We further leverage longitudinal data in a subgroup of 81 children with ASD and show that the level of social orienting at baseline is a significant predictor of developmental gains and treatment outcome. These results pave the way for identifying subgroups of children who show a better response to early and intensive intervention, a first step toward precision medicine for children with autism.

2. Using 2D Video-based Pose Estimation for Automated Prediction of Autism Spectrum Disorders in Preschoolers

   Kojovic, N.*, Natraj, S.*, Mohanty, S. P., Maillart, T., and Schaer, M.

   Scientific Reports 2021

   Abstract URL PDF

   Clinical research in autism has recently witnessed promising digital phenotyping results, mainly focused on single feature extraction, such as gaze, head turn on name-calling or visual tracking of the moving object. The main drawback of these studies is the focus on relatively isolated behaviors elicited by largely controlled prompts. We recognize that while the diagnosis process understands the indexing of the specific behaviors, ASD also comes with broad impairments that often transcend single behavioral acts. For instance, the atypical nonverbal behaviors manifest through global patterns of atypical postures and movements, fewer gestures used and often decoupled from visual contact, facial affect, speech. Here, we tested the hypothesis that a deep neural network trained on the non-verbal aspects of social interaction can effectively differentiate between children with ASD and their typically developing peers. Our model achieves an accuracy of 80.9% (F1 score: 0.818; precision: 0.784; recall: 0.854) with the prediction probability positively correlated to the overall level of symptoms of autism in social affect and repetitive and restricted behaviors domain. Provided the non-invasive and affordable nature of computer vision, our approach carries reasonable promises that a reliable machine-learning-based ASD screening may become a reality not too far in the future.

3. Early alterations of large-scale brain networks temporal dynamics in young children with autism

   Bochet, A.*, Sperdin, H. F.*, Rihs, T. A., Kojovic, N., Franchini, M., Jan, R. K., Michel, C. M., and Schaer, M.

   Communications Biology 2021

   Abstract URL PDF

   Autism spectrum disorders (ASD) are associated with disruption of large-scale brain net- work. Recently, we found that directed functional connectivity alterations of social brain networks are a core component of atypical brain development at early developmental stages in ASD. Here, we investigated the spatio-temporal dynamics of whole-brain neuronal net- works at a subsecond scale in 113 toddlers and preschoolers (66 with ASD) using an EEG microstate approach. We first determined the predominant microstates using established clustering methods. We identified five predominant microstate (labeled as microstate classes A–E) with significant differences in the temporal dynamics of microstate class B between the groups in terms of increased appearance and prolonged duration. Using Markov chains, we found differences in the dynamic syntax between several maps in toddlers and preschoolers with ASD compared to their TD peers. Finally, exploratory analysis of brain–behavioral relationships within the ASD group suggested that the temporal dynamics of some maps were related to conditions comorbid to ASD during early developmental stages.

4. Preprint

   Distinct patterns of treatment response using the Early Start Denver Model with young children with autism spectrum disorder: a cluster analysis

   Godel, M.*, Robain, F.*, Kojovic, N., Franchini, M., Wilde, H., and Schaer, M.

   medRxiv 2021

   Abstract URL PDF

   Evidence-based early intervention approaches have been shown to significantly improve many areas of development in young children with autism. Despite having an overall positive impact for most children, there is high inter-individual heterogeneity of response to treatment, and it is currently not possible to predict which child will benefit from which specific intervention. In this study, we analyze developmental trajectories of young children with autism who received two-years of Early Start Denver Model intervention in Geneva, Switzerland (n=47). Using cluster analyses, we distinguish between 3 subgroups based on cognitive level at baseline and rates of change over time. The first subgroup of children had cognitive scores at baseline only slightly below what would be expected for their age and were found to have nearly no cognitive delay by the end of treatment (High at Baseline: HB). The children in the two other subgroups all presented with severe cognitive delay at baseline, with the second group’s cognitive scores improving significantly in the first year of intervention, along with increased communication and daily living skills (High Responders: HR). The third subgroup showed little to no cognitive level change over the course of treatment (Minimal Responders: MR). Furthermore, the rates of change in cognition and adaptative behavior in the HR subgroup were already significantly higher compared to the MR subgroup within the first 6 months of intervention. A rapid and early response to intervention might thus represent a predictor of optimal outcome. Inversely, slower progress by the sixth month of intervention may predict that the child will have a slower response to the treatment overall and may need alternative supports to reach their learning objectives quickly.

5. Preprint

   Distinct profiles of spatio-temporal brain dynamics along symptoms dimensions in autism

   Mullier, E., Kojovic, N., Denervaud, S., Vohryzek, J., Hagmann, P., and Schaer, M.

   bioRxiv 2021

   Abstract URL PDF

   Autism Spectrum Disorders are accompanied by atypical brain activity and impairments in brain connectivity. In particular, dynamic functional connectivity approaches highlighted aberrant brain fluctuations at rest in individuals with autism compared to a group composed of typically developed individuals, matched in age and gender. However, the characterization of these variations remains unclear. Here, we quantified the spatio-temporal network dynamics using two novel dynamic group-based measures, namely system diversity and spatio-temporal diversity. Using the public database ABIDE 1, we explored the differences between individuals with autism and typically developed individuals. Our results show evidence that individuals with autism have atypical connectivity patterns over time characterized by a lower integration of heterogeneous cognitive processes and unstable functional activity, except for the default mode network presenting its own specific dynamic pattern. Within the autism group, we find this pattern of results to be stronger in more severely affected patients with a predominance of symptoms in the social affect domain. However, patients with prominently restricted and repetitive behaviours demonstrate a more conservative profile of brain dynamics characterized by a lower spatio-temporal diversity of the default mode network.

6. Measuring the Emergence of Specific Abilities in Young Children with Autism Spectrum Disorders: The Example of Early Hyperlexic Traits

   Solazzo, S., Kojovic, N., Robain, F., and Schaer, M.

   Brain Sciences 2021

   Abstract URL PDF

   The presence of a restricted interest in written materials, including an early ability to name and recognize letters and numbers, is regularly reported in preschoolers with autism spectrum disorders (ASDs). There is, however, scarce information on this early ability akin to emerging hyperlexic traits in preschoolers with ASD younger than 3 years old. Here, we defined a measure of early naming and recognition of letters and numbers in 155 preschoolers with ASD using a sliding window approach combined with a 90th percentile threshold criterion, and subsequently compared the profiles of children with ASD with and without early hyperlexic traits. Using this measure, we found that 9% of children with ASD showed early hyperlexic traits. The early ability to name and recognize letters and numbers was associated with a higher level of restricted and repetitive behaviors yet more social-oriented behaviors at baseline and with better expressive and written communication at baseline and one year later. This study contributes to a better definition of the profile of children with ASD with an early ability in letters and numbers akin to emerging hyperlexic traits, a skill that is associated with promising social strengths and language abilities in this subgroup of children.

7. Altered Gray-White Matter Boundary Contrast in Toddlers at Risk for Autism Relates to Later Diagnosis of Autism Spectrum Disorder

   Godel, M., Andrews, D. S., Amaral, D. G., Ozonoff, S., Young, G. S., Lee, J. S., Nordahl, C. W.*, and Schaer, M.*

   Frontiers in Neuroscience 2021

   Abstract URL PDF

   Background: Recent neuroimaging studies have highlighted differences in cerebral maturation in individuals with autism spectrum disorder (ASD) in comparison to typical development. For instance, the contrast of the gray-white matter boundary is decreased in adults with ASD. To determine how gray-white matter boundary integrity relates to early ASD phenotypes, we used a regional structural MRI index of gray-white matter contrast (GWC) on a sample of toddlers with a hereditary high risk for ASD. Methods: We used a surface-based approach to compute vertex-wise GWC in a longitudinal cohort of toddlers at high-risk for ASD imaged twice between 12 and 24 months (n=20). A full clinical assessment of ASD-related symptoms was performed in conjunction with imaging and again at three years of age for diagnostic outcome. Three outcome groups were defined (ASD, n=9; typical development, n=8; non-typical development, n=3). Results: ASD diagnostic outcome at age 3 was associated with widespread increases in GWC between age 12 and 24 months. Many cortical regions were affected, including regions implicated in social processing and language acquisition. In parallel, we found that early onset of ASD symptoms (i.e. prior to 18-months) was specifically associated with slower GWC rates of change during the second year of life. These alterations were found in areas mainly belonging to the central executive network. Limitations: Our study is the first to measure maturational changes in GWC in toddlers who developed autism, but given the limited size of our sample results should be considered exploratory and warrant further replication in independent and larger samples. Conclusion: These preliminary results suggest that ASD is linked to early alterations of the gray-white matter boundary in widespread brain regions. Early onset of ASD diagnosis constitutes an independent clinical parameter associated with a specific corresponding neurobiological developmental trajectory. Altered neural migration and/or altered myelination processes potentially explain these findings.

8. Preprint

   Trajectories of imitation skills in preschoolers with Autism Spectrum Disorders

   Pittet, I., Kojovic, N., Franchini, M., and Schaer, M.

   medRxiv 2021

   Abstract URL PDF

   Imitation skills play a crucial role in social cognitive development from early childhood. Many studies have shown a deficit in imitation skills in children with Autism Spectrum Disorders (ASD). Little is known about the development of imitation behaviors in children with ASD. This study aims to measure the trajectories of early imitation skills in preschoolers with ASD and how these skills impact other areas of early development. For this purpose, we assessed imitation, language and cognition skills in 177 children with ASD and 43 typically developing children (TD) aged 2 to 5 years old, 126 of which were followed longitudinally, yielding a total of 396 time-points. Our results confirmed the presence of an early imitation deficit in toddlers with ASD compared to TD children. The study of the trajectories showed that these difficulties were marked at the age of two years, and gradually decreased until the age of 5 years old. Imitation skills were strongly linked with cognitive, language skills and level of symptoms in our ASD group at baseline. Moreover, the imitation skills at baseline were predictive of the language gains a year later in our ASD group. Using a data-driven clustering method, we delineated different developmental trajectories of imitation skills within the ASD group. The clinical implications of the findings are discussed, particularly the impact of an early imitation deficit on other areas of competence of the young child.

9. Structural control energy of resting-state functional brain states reveals less cost-effective brain dynamics in psychosis vulnerability

   Zöller, D., Sandini, C., Schaer, M., Eliez, S., Bassett, D. S., and Van De Ville, D.

   Hum Brain Mapp 2021

2020

1. Preprint

   Unraveling the Developmental Dynamic of Visual Exploration of Social Interactions in Autism

   Kojovic, N., Franchini, M., Sperdin, H. F., Sandini, C., Jan, R. K., Zöller, D., and Schaer, M.

   bioRxiv 2020

   Abstract URL PDF

   Atypical deployment of social gaze is present early on in toddlers with autism spectrum disorders (ASDs). Yet, studies characterizing the developmental dynamic behind it are scarce. Here we used a data-driven method to delineate the developmental change in visual exploration of social interaction over childhood years in autism. Longitudinal eye-tracking data were acquired as children with ASD and their typically developing (TD) peers freely explored complex animated scene. We found divergent moment-to moment gaze patterns in children with ASD compared to their TD peers. This divergence was particularly evident in sequences that displayed social interactions between characters, and even more so in the children with lower developmental and functional levels. Basic visual properties of the animated scene did not accounted for the enhanced divergence. Over childhood years, these differences dramatically increased to become more idiosyncratic. Taken together, these findings suggest that social attention should be targeted early in clinical treatments.

2. Emotional vs. Neutral Face Exploration and Habituation: An Eye-Tracking Study of Preschoolers With Autism Spectrum Disorders

   Bochet, A., Franchini, M., Kojovic, N., Glaser, B., and Schaer, M.

   Front Psychiatry 2020

   Abstract URL PDF

   Diminished orienting to social stimuli, and particularly to faces, is a core feature of autism spectrum disorders (ASDs). Impaired face processing has been linked to atypical attention processes that trigger a cascade of pathological development contributing to impaired social communication. The aim of the present study is to explore the processing of emotional and neutral faces using an eye-tracking paradigm (the emotional faces task) with a group of 24 children with ASD aged 6 and under and a group of 22 age-matched typically developing (TD) children. We also measure habituation to faces in both groups based on the presentation of repeated facial expressions. Specifically, the task consists of 32 pairs of faces, a neutral face and an emotional face from the same identity, shown side by side on the screen. We observe differential exploration of emotional faces in preschoolers with ASD compared with TD. Participants with ASD make fewer fixations to emotional faces than their TD peers, and the duration of their first fixation on emotional faces is equivalent to their first fixation on neutral faces. These results suggest that emotional faces may be less interesting for children with ASD. We also observe a habituation process to neutral faces in both children with ASD and TD, who looked less at neutral faces during the last quarter of the task compared with the first quarter. By contrast, TD children show increased interest in emotional faces throughout the task, looking slightly more at emotional faces during the last quarter of the task than during the first quarter. Children with ASD demonstrate neither habituation nor increased interest in the changing emotional expressions over the course of the task, looking at the stimuli for equivalent time throughout the task. A lack of increased interest in emotional faces may suggest a lack of sensitivity to changes in expression in young children with ASD.

3. Identifying neurodevelopmental anomalies of white matter microstructure associated with high risk for psychosis in 22q11.2DS

   Bagautdinova, J., Padula, M. C., Zöller, D., Sandini, C., Schneider, M., Schaer, M., and Eliez, S.

   Transl Psychiatry 2020
4. Abnormal Development and Dysconnectivity of Distinct Thalamic Nuclei in Patients With 22q11.2 Deletion Syndrome Experiencing Auditory Hallucinations

   Mancini, V., Zöller, D., Schneider, M., Schaer, M., and Eliez, S.

   Biol Psychiatry Cogn Neurosci Neuroimaging 2020
5. Predictors of Treatment Outcome in Preschoolers with Autism Spectrum Disorder: An Observational Study in the Greater Geneva Area, Switzerland

   Robain, F., Franchini, M., Kojovic, N., Wilde, H., and Schaer, M.

   J Autism Dev Disord 2020

   Abstract URL PDF

   This study aims to identify predictors of treatment outcome in young children with ASD within a European context, where service provision of intervention remains sporadic. We investigated whether a child’s age at baseline, intensity of the intervention provided, type of intervention, child’s level of social orienting and cognitive skills at baseline predicted changes in autistic symptoms and cognitive development after 1 year of intervention, in a sample of 60 children with ASD. Our results strongly support early and intensive intervention. We also observed that lower cognitive skills at baseline were related to greater cognitive gains. Finally, we show that a child’s interest in social stimuli may contribute to intervention outcome.

6. Developmental Trajectories of Cortical Thickness in Relation to Schizotypy During Adolescence

   Derome, M., Tonini, E., Zöller, D., Schaer, M., Eliez, S., and Debbané, M.

   Schizophr Bull 2020
7. Developmental trajectories of subcortical structures in relation to dimensional schizotypy expression along adolescence

   Derome, M., Zöller, D., Modinos, G., Schaer, M., Eliez, S., and Debbané, M.

   Schizophr Res 2020
8. Favorable effects of omega-3 polyunsaturated fatty acids in attentional control and conversion rate to psychosis in 22q11.2 deletion syndrome

   Armando, M., Ciampoli, M., Padula, M. C., Amminger, P., De Crescenzo, F., Maeder, J., Schneider, M., Schaer, M., Managò, F., Eliez, S., and Papaleo, F.

   Neuropharmacology 2020
9. Dynamic spatiotemporal patterns of brain connectivity reorganize across development

   Vohryzek, J., Griffa, A., Mullier, E., Friedrichs-Maeder, C., Sandini, C., Schaer, M., Eliez, S., and Hagmann, P.

   Netw Neurosci 2020
10. Pituitary dysmaturation affects psychopathology and neurodevelopment in 22q11.2 Deletion Syndrome

    Sandini, C., Chambaz, M., Schneider, M., Armando, M., Zöller, D., Schaer, M., Sandi, C., Van De Ville, D., and Eliez, S.

    Psychoneuroendocrinology 2020
11. Positive psychotic symptoms are associated with divergent developmental trajectories of hippocampal volume during late adolescence in patients with 22q11DS

    Mancini, V., Sandini, C., Padula, M. C., Zöller, D., Schneider, M., Schaer, M., and Eliez, S.

    Mol Psychiatry 2020

2019

1. Sensory Processing Issues and Their Association with Social Difficulties in Children with Autism Spectrum Disorders

   Kojovic, N., Ben Hadid, L., Franchini, M., and Schaer, M.

   J Clin Med 2019

   Abstract URL PDF

   Sensory processing issues have been frequently reported in individuals with Autism Spectrum Disorders (ASD), but their relationship with social and overall adaptive functioning has not been extensively characterized to date. Here, we investigate how sensory processing atypicalities relate with deficits in social skills, impaired social cognition, and general adaptive functioning in a group of preschoolers with ASD. Sixty-four children with ASD aged 3 to 6 were included in this study, along with 36 age-matched typically-developing (TD) peers. Parent-reported measures of sensory processing, social difficulties and overall adaptive functioning were collected for all children. We also obtained precise measures of social attention deployment using a custom-design eye-tracking task depicting naturalistic social scenes. Within the group of children with ASD, higher intensities of sensory issues were associated with more prominent social difficulties and lower adaptive functioning. We also found that children with ASD who had more sensory issues showed visual exploration patterns of social scenes that strongly deviated from the one seen in the TD group. The association of sensory processing atypicalities with “higher-order” functional domains such as social and adaptive functioning in children with ASD stresses the importance of further research on sensory symptoms in autism.

2. Neural Processing of Dynamic Animated Social Interactions in Young Children With Autism Spectrum Disorder: A High-Density Electroencephalography Study

   Jan, R. K., Rihs, T. A., Kojovic, N., Sperdin, H. F., Franchini, M., Custo, A., Tomescu, M. I., Michel, C. M., and Schaer, M.

   Front Psychiatry 2019

   Abstract URL PDF

   Background: Atypical neural processing of social visual information contributes to impaired social cognition in autism spectrum disorder. However, evidence for early developmental alterations in neural processing of social contingencies is scarce. Most studies in the literature have been conducted in older children and adults. Here, we aimed to investigate alterations in neural processing of social visual information in children with autism spectrum disorder compared to age-matched typically developing peers. Methods: We used a combination of 129-channel electroencephalography and high-resolution eye-tracking to study differences in the neural processing of dynamic cartoons containing human-like social interactions between 14 male children with autism spectrum disorder and 14 typically developing male children, aged 2–5 years. Using a microstate approach, we identified four prototypical maps in both groups and compared the temporal characteristics and inverse solutions (activation of neural sources) of these maps between groups. Results: Inverse solutions of the group maps that were most dominant during free viewing of the dynamic cartoons indicated decreased prefrontal and cingulate activation, impaired activation of the premotor cortex, and increased activation of parietal, temporal, occipital, and cerebellar regions in children with autism spectrum disorder compared to their typically developing peers. Conclusions: Our findings suggest that impairments in brain regions involved in processing social contingencies embedded in dynamic cartoons are present from an early age in autism spectrum disorder. To the best of our knowledge, this is the first study to investigate neural processing of social interactions of children with autism spectrum disorder using dynamic semi-naturalistic stimuli.

3. Large-Scale Brain Network Dynamics Provide a Measure of Psychosis and Anxiety in 22q11.2 Deletion Syndrome

   Zöller, D., Sandini, C., Karahanoğlu, F. I., Padula, M. C., Schaer, M., Eliez, S., and Van De Ville, D.

   Biol Psychiatry Cogn Neurosci Neuroimaging 2019
4. The brain-structural correlates of mathematical expertise

   Popescu, T., Sader, E., Schaer, M., Thomas, A., Terhune, D. B., Dowker, A., Mars, R. B., and Cohen Kadosh, R.

   Cortex 2019
5. Robust Recovery of Temporal Overlap Between Network Activity Using Transient-Informed Spatio-Temporal Regression

   Zoller, D. M., Bolton, T. A. W., Karahanoglu, F. I., Eliez, S., Schaer, M., and Van De Ville, D.

   IEEE Trans Med Imaging 2019
6. Initiation of joint attention and related visual attention processes in infants with autism spectrum disorder: Literature review

   Franchini, M., Armstrong, V. L., Schaer, M., and Smith, I. M.

   Child Neuropsychol 2019

   Abstract URL

   Autism spectrum disorder (ASD) represents a group of neurodevelopmental disabilities that can be difficult to identify before the age of 2 or 3 years, the age when the full range of behavioral symptoms has emerged in most cases. Initiation of joint attention is an important developmental function in which impairments are already observable before the second birthday and can predict children’s ASD symptomatology. In the first part of this review, we summarize results pertaining to retrospective studies of initiation of joint attention in children with ASD and prospective studies of infants at high risk for ASD during the first 2 years, when this behavior is becoming more complex in terms of frequency, quality, and variety. We will also discuss the implications of impairments in dyadic engagement, a precursor of joint attention behavior, for the early development of joint attention. Finally, the early development of initiation of joint attention has been related to specific visual attention mechanisms such as social orienting and visual disengagement. In the second part of this review, we provide an overview of the relationship between those visual attention mechanisms and subsequent social-communication impairments. Clinical and research implications of these findings for both early detection and early intervention will be discussed.

7. A Longitudinal Study of Local Gyrification Index in Young Boys With Autism Spectrum Disorder

   Libero, L. E., Schaer, M., Li, D. D., Amaral, D. G., and Nordahl, C. W.

   Cereb Cortex 2019

   Abstract URL PDF

   Local gyrification index (LGI), a metric quantifying cortical folding, was evaluated in 105 boys with autism spectrum disorder (ASD) and 49 typically developing (TD) boys at 3 and 5 years-of-age. At 3 years-of-age, boys with ASD had reduced gyrification in the fusiform gyrus compared with TD boys. A longitudinal evaluation from 3 to 5 years revealed that while TD boys had stable/decreasing LGI, boys with ASD had increasing LGI in right inferior temporal gyrus, right inferior frontal gyrus, right inferior parietal lobule, and stable LGI in left lingual gyrus. LGI was also examined in a previously defined neurophenotype of boys with ASD and disproportionate megalencephaly. At 3 years-of-age, this subgroup exhibited increased LGI in right dorsomedial prefrontal cortex, cingulate cortex, and paracentral cortex, and left cingulate cortex and superior frontal gyrus relative to TD boys and increased LGI in right paracentral lobule and parahippocampal gyrus, and left precentral gyrus compared with boys with ASD and normal brain size. In summary, this study identified alterations in the pattern and development of LGI during early childhood in ASD. Distinct patterns of alterations in subgroups of boys with ASD suggests that multiple neurophenotypes exist and boys with ASD and disproportionate megalencephaly should be evaluated separately.

2018

1. A Mini Review on the Contribution of the Anterior Cingulate Cortex in the Risk of Psychosis in 22q11.2 Deletion Syndrome

   Padula, M. C., Scariati, E., Schaer, M., and Eliez, S.

   Front Psychiatry 2018
2. Face processing in 22q11.2 deletion syndrome: atypical development and visual scanning alterations

   Zaharia, A., Schneider, M., Glaser, B., Franchini, M., Menghetti, S., Schaer, M., Debbané, M., and Eliez, S.

   J Neurodev Disord 2018
3. Deficits in mesolimbic reward pathway underlie social interaction impairments in children with autism

   Supekar, K., Kochalka, J., Schaer, M., Wakeman, H., Qin, S., Padmanabhan, A., and Menon, V.

   Brain 2018

   Abstract URL PDF

   Lack of interest in social interaction is a hallmark of autism spectrum disorder. Animal studies have implicated the mesolimbic reward pathway in driving and reinforcing social behaviour, but little is known about the integrity of this pathway and its behavioural consequences in children with autism spectrum disorder. Here we test the hypothesis that the structural and functional integrity of the mesolimbic reward pathway is aberrant in children with autism spectrum disorder, and these aberrancies contribute to the social interaction impairments. We examine structural and functional connectivity of the mesolimbic reward pathway in two independent cohorts totalling 82 children aged 7-13 years with autism spectrum disorder and age-, gender-, and intelligence quotient-matched typically developing children (primary cohort: children with autism spectrum disorder n = 24, typically developing children n = 24; replication cohort: children with autism spectrum disorder n = 17, typically developing children n = 17), using high angular resolution diffusion-weighted imaging and functional MRI data. We reliably identify white matter tracts linking-the nucleus accumbens and the ventral tegmental area-key subcortical nodes of the mesolimbic reward pathway, and provide reproducible evidence for structural aberrations in these tracts in children with autism spectrum disorder. Further, we show that structural aberrations are accompanied by aberrant functional interactions between nucleus accumbens and ventral tegmental area in response to social stimuli. Crucially, we demonstrate that both structural and functional circuit aberrations in the mesolimbic reward pathway are related to parent-report measures of social interaction impairments in affected children. Our findings, replicated across two independent cohorts, reveal that deficits in the mesolimbic reward pathway contribute to impaired social skills in childhood autism, and provide fundamental insights into neurobiological mechanisms underlying reduced social interest in humans.

4. Development of Structural Covariance From Childhood to Adolescence: A Longitudinal Study in 22q11.2DS

   Sandini, C., Zöller, D., Scariati, E., Padula, M. C., Schneider, M., Schaer, M., Van De Ville, D., and Eliez, S.

   Front Neurosci 2018
5. Cortical Dysconnectivity Measured by Structural Covariance Is Associated With the Presence of Psychotic Symptoms in 22q11.2 Deletion Syndrome

   Sandini, C., Scariati, E., Padula, M. C., Schneider, M., Schaer, M., Van De Ville, D., and Eliez, S.

   Biol Psychiatry Cogn Neurosci Neuroimaging 2018
6. Early Adaptive Functioning Trajectories in Preschoolers With Autism Spectrum Disorders

   Franchini, M., Zöller, D., Gentaz, E., Glaser, B., Wilde, H., Kojovic, N., Eliez, S., and Schaer, M.

   J Pediatr Psychol 2018

   Abstract URL PDF

   Background: In preschoolers with autism spectrum disorder (ASD) symptom, severity has a negative impact on the development of adaptive functioning, with critical consequences on the quality of life of those children. Developmental features such as reduced social interest or the presence of behavioral problems can further impede daily life learning experiences. Objectives: The first aim of this study is to confirm the negative impact of high symptom severity on adaptive functioning trajectories in preschoolers with ASD. The second objective intends to explore whether reduced social interest and severe behavioral problems negatively affect developmental trajectories of adaptive functioning in young children with ASD. Methods: In total, 68 children with ASD and 48 age and gender-matched children with typical development (TD) between 1.6 and 6 years were included in our study, and longitudinal data on adaptive functioning were collected (mean length of the longitudinal data collection was 1.4 years ± 0.6). Baseline measures of symptom severity, social interest, and behavioral problems were also obtained. Results: We confirmed that children with ASD show parallel developmental trajectories but a significantly lower performance of adaptive functioning compared with children with TD. Furthermore, analyses within ASD children demonstrated that those with higher symptom severity, reduced social interest, and higher scores of behavioral problems exhibited especially lower or faster declining trajectories of adaptive functioning. Conclusions: These findings bolster the idea that social interest and behavioral problems are crucial for the early adaptive functioning development of children with autism. The current study has clinical implications in pointing out early intervention targets in children with ASD.

7. Coping Strategies Mediate the Effect of Stressful Life Events on Schizotypal Traits and Psychotic Symptoms in 22q11.2 Deletion Syndrome

   Armando, M., Sandini, C., Chambaz, M., Schaer, M., Schneider, M., and Eliez, S.

   Schizophr Bull 2018
8. Early alterations of social brain networks in young children with autism

   Sperdin, H. F., Coito, A., Kojovic, N., Rihs, T. A., Jan, R. K., Franchini, M., Plomp, G., Vulliemoz, S., Eliez, S., Michel, C. M., and Schaer, M.

   Elife 2018

   Abstract URL PDF

   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. We recorded the gaze patterns and brain activity of toddlers with ASD and their typically developing peers while they explored dynamic social scenes. Directed functional connectivity analyses based on electrical source imaging revealed frequency specific network atypicalities in the theta and alpha frequency bands, manifesting as alterations in both the driving and the connections from key nodes of the social brain associated with autism. 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 less atypical gaze patterns and lower clinical impairment. 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.

9. Cortical morphology development in patients with 22q11.2 deletion syndrome at ultra-high risk of psychosis

   Padula, M. C., Schaer, M., Armando, M., Sandini, C., Zöller, D., Scariati, E., Schneider, M., and Eliez, S.

   Psychol Med 2018
10. Psychotic symptoms influence the development of anterior cingulate BOLD variability in 22q11.2 deletion syndrome

    Zöller, D., Padula, M. C., Sandini, C., Schneider, M., Scariati, E., Van De Ville, D., Schaer, M., and Eliez, S.

    Schizophr Res 2018

2017

1. Salivary Cortisol and Regional Brain Volumes Among Veterans With and Without Posttraumatic Stress Disorder

   Babson, K. A., Woodward, S. H., Schaer, M., Sephton, S. E., and Kaloupek, D. G.

   Biol Psychiatry Cogn Neurosci Neuroimaging 2017
2. Quantifying indices of short- and long-range white matter connectivity at each cortical vertex

   Schaer, M.*, Padula, M. C.*, Scariati, E., Mutlu, A. K., Zöller, D., Schneider, M., and Eliez, S.

   PLoS One 2017

   Abstract URL PDF

   Several neurodevelopmental diseases are characterized by impairments in cortical morphology along with altered white matter connectivity. However, the relationship between these two measures is not yet clear. In this study, we propose a novel methodology to compute and display metrics of white matter connectivity at each cortical point. After co-registering the extremities of the tractography streamlines with the cortical surface, we computed two measures of connectivity at each cortical vertex: the mean tracts’ length, and the proportion of short- and long-range connections. The proposed measures were tested in a clinical sample of 62 patients with 22q11.2 deletion syndrome (22q11DS) and 57 typically developing individuals. Using these novel measures, we achieved a fine-grained visualization of the white matter connectivity patterns at each vertex of the cortical surface. We observed an intriguing pattern of both increased and decreased short- and long-range connectivity in 22q11DS, that provides novel information about the nature and topology of white matter alterations in the syndrome. We argue that the method presented in this study opens avenues for additional analyses of the relationship between cortical properties and patterns of underlying structural connectivity, which will help clarifying the intrinsic mechanisms that lead to altered brain structure in neurodevelopmental disorders.

3. The Default Mode Network in Autism

   Padmanabhan, A., Lynch, C. J., Schaer, M., and Menon, V.

   Biol Psychiatry Cogn Neurosci Neuroimaging 2017

   Abstract URL PDF

   Autism spectrum disorder (ASD) is characterized by deficits in social communication and interaction. Since its discovery as a major functional brain system, the default mode network (DMN) has been implicated in a number of psychiatric disorders, including ASD. We review converging multimodal evidence for DMN dysfunction in the context of specific components of social cognitive dysfunction in ASD—self-referential processing, which is the ability to process social information relative to oneself; and theory of mind or mentalizing, which is the ability to infer the mental states, such as beliefs, intentions, and emotions, of others. We show that altered functional and structural organization of the DMN and its atypical developmental trajectory are prominent neurobiological features of ASD. We integrate findings on atypical cytoarchitectonic organization and imbalance in excitatory-inhibitory circuits, which alter local and global brain signaling, to scrutinize putative mechanisms underlying DMN dysfunction in ASD. Our synthesis of the extant literature suggests that aberrancies in key nodes of the DMN and their dynamic functional interactions contribute to atypical integration of information about the self in relation to “other” as well as to impairments in the ability to flexibly attend to socially relevant stimuli. We conclude by highlighting open questions for future research.

4. MRIQC: Advancing the automatic prediction of image quality in MRI from unseen sites

   Esteban, O., Birman, D., Schaer, M., Koyejo, O. O., Poldrack, R. A., and Gorgolewski, K. J.

   PLoS One 2017

   Abstract URL PDF

   Quality control of MRI is essential for excluding problematic acquisitions and avoiding bias in subsequent image processing and analysis. Visual inspection is subjective and impractical for large scale datasets. Although automated quality assessments have been demonstrated on single-site datasets, it is unclear that solutions can generalize to unseen data acquired at new sites. Here, we introduce the MRI Quality Control tool (MRIQC), a tool for extracting quality measures and fitting a binary (accept/exclude) classifier. Our tool can be run both locally and as a free online service via the OpenNeuro.org portal. The classifier is trained on a publicly available, multi-site dataset (17 sites, N = 1102). We perform model selection evaluating different normalization and feature exclusion approaches aimed at maximizing across-site generalization and estimate an accuracy of 76%±13% on new sites, using leave-one-site-out cross-validation. We confirm that result on a held-out dataset (2 sites, N = 265) also obtaining a 76% accuracy. Even though the performance of the trained classifier is statistically above chance, we show that it is susceptible to site effects and unable to account for artifacts specific to new sites. MRIQC performs with high accuracy in intra-site prediction, but performance on unseen sites leaves space for improvement which might require more labeled data and new approaches to the between-site variability. Overcoming these limitations is crucial for a more objective quality assessment of neuroimaging data, and to enable the analysis of extremely large and multi-site samples.

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

   Padula, M. C., Scariati, E., Schaer, M., Sandini, C., Ottet, M. C., Schneider, M., Van De Ville, D., and Eliez, S.

   Neuroimage Clin 2017
6. Social orienting and joint attention in preschoolers with autism spectrum disorders

   Franchini, M., Glaser, B., Wilde, H., Gentaz, E., Eliez, S., and Schaer, M.

   PLoS One 2017

   Abstract URL PDF

   Children with Autism Spectrum Disorders (ASD) orient less to socially salient stimuli, such as dynamic social images, than typically developing children. In turn, this lack of social orienting is thought to impair affected individuals’ socio communicative development. Here, we aim to explore the relationship between time spent on dynamic social images and ASD behaviors, such as joint attention and communication, in preschoolers on the autism spectrum. In this study, social orienting is measured using eye-tracking during a task consisting of side-by-side presentations of dynamic social images and dynamic geometric images. The side of the screen where each type of video was presented alternated between items to avoid visual perseveration from influencing the location of participants’ first fixations. Visual exploration patterns recorded during the task from 33 preschoolers with ASD were compared with those of 27 typical developing (TD) children. Additionally, we quantified joint attention behaviors and used standardized parent reports to measure communication. We observed reduced orienting to dynamic social images in preschoolers with ASD compared to TD children. Also, ASD participants went to the dynamic social images less frequently for their first fixations. However, we observed great heterogeneity within the ASD group. ASD preschoolers who spent more time on the dynamic social images also presented more pronounced visual engagement with the dynamic social images (longer mean fixation duration and fewer saccades per second). Moreover, in the ASD group, more time spent on dynamic social images correlated with increased frequency of joint attention behaviors, which in turn correlated with improved communication skills. Our results support reduced social orienting in children with ASD, which correlated with their visual exploration patterns. Further, reduced orienting to the social world in young children with ASD is related to socio communicative deficits and should, therefore, be a focus of intervention programs as early as possible.

7. Impact of the Early Start Denver Model on the cognitive level of children with autism spectrum disorder: study protocol for a randomised controlled trial using a two-stage Zelen design

   Touzet, S., Occelli, P., Schröder, C., Manificat, S., Gicquel, L., Stanciu, R., Schaer, M., Oreve, M. J., Speranza, M., Denis, A., Zelmar, A., Falissard, B., Georgieff, N., Bahrami, S., Geoffray, M. M., Grisi, S., Marignier, S., Useo, J. M., Pourrat, A., Peter, C., Mengarelli, F., Gallifet, N., Rumillat, F., Tenant, G., Sonié, S., Zimmerman, M., Malo, V., Jacob, C. G., Bahrami, S., Queste, C., Raffeneau, F., Gilet, S., Ammeloot, M., Danion-Grilliat, A., Florence, E., Vecchionacci, V., Janssen, L., Dubrovskaya, A., Rohmer, M., Lambs, B., Delvenne, V., Carlier, S., Ducenne, L., Colin, C., and Bouveret, L.

   BMJ Open 2017
8. Subthreshold Psychosis in 22q11.2 Deletion Syndrome: Multisite Naturalistic Study

   Weisman, O., Guri, Y., Gur, R. E., McDonald-McGinn, D. M., Calkins, M. E., Tang, S. X., Emanuel, B., Zackai, E. H., Eliez, S., Schneider, M., Schaer, M., Kates, W. R., Antshel, K. M., Fremont, W., Shashi, V., Hooper, S. R., Armando, M., Vicari, S., Pontillo, M., Kushan, L., Jalbrzikowski, M., Bearden, C. E., Cubells, J. F., Ousley, O. Y., Walker, E. F., Simon, T. J., Stoddard, J., Niendam, T. A., Bree, M. B. M., and Gothelf, D.

   Schizophr Bull 2017
9. Disentangling resting-state BOLD variability and PCC functional connectivity in 22q11.2 deletion syndrome

   Zöller, D., Schaer, M., Scariati, E., Padula, M. C., Eliez, S., and Van De Ville, D.

   Neuroimage 2017
10. Morphological brain changes associated with negative symptoms in patients with 22q11.2 Deletion Syndrome

    Mihailov, A., Padula, M. C., Scariati, E., Schaer, M., Schneider, M., and Eliez, S.

    Schizophr Res 2017
11. Multimodal investigation of triple network connectivity in patients with 22q11DS and association with executive functions

    Padula, M. C., Schaer, M., Scariati, E., Maeder, J., Schneider, M., and Eliez, S.

    Hum Brain Mapp 2017
12. Cortical Alterations in Medication-Overuse Headache

    Riederer, F., Schaer, M., Gantenbein, A. R., Luechinger, R., Michels, L., Kaya, M., Kollias, S., and Sándor, P. S.

    Headache 2017

2016

1. Visual memory profile in 22q11.2 microdeletion syndrome: are there differences in performance and neurobiological substrates between tasks linked to ventral and dorsal visual brain structures? A cross-sectional and longitudinal study

   Bostelmann, M., Schneider, M., Padula, M. C., Maeder, J., Schaer, M., Scariati, E., Debbané, M., Glaser, B., Menghetti, S., and Eliez, S.

   J Neurodev Disord 2016
2. Aberrant Development of Speech Processing in Young Children with Autism: New Insights from Neuroimaging Biomarkers

   Sperdin, H. F., and Schaer, M.

   Front Neurosci 2016

   Abstract URL PDF

   From the time of birth, a newborn is continuously exposed and naturally attracted to human voices, and as he grows, he becomes increasingly responsive to these speech stimuli, which are strong drivers for his language development and knowledge acquisition about the world. In contrast, young children with autism spectrum disorder (ASD) are often insensitive to human voices, failing to orient and respond to them. Failure to attend to speech in turn results in altered development of language and social-communication skills. Here, we review the critical role of orienting to speech in ASD, as well as the neural substrates of human voice processing. Recent functional neuroimaging and electroencephalography studies demonstrate that aberrant voice processing could be a promising marker to identify ASD very early on. With the advent of refined brain imaging methods, coupled with the possibility of screening infants and toddlers, predictive brain function biomarkers are actively being examined and are starting to emerge. Their timely identification might not only help to differentiate between phenotypes, but also guide the clinicians in setting up appropriate therapies, and better predicting or quantifying long-term outcome.

3. Brief Report: A Preference for Biological Motion Predicts a Reduction in Symptom Severity 1 Year Later in Preschoolers with Autism Spectrum Disorders

   Franchini, M., Wilde, H., Glaser, B., Gentaz, E., Eliez, S., and Schaer, M.

   Front Psychiatry 2016

   Abstract URL PDF

   Recent research has consistently demonstrated reduced orienting to social stimuli in samples of young children with autism spectrum disorders (ASD). However, social orienting greatly varies between individual children on the spectrum. Better understanding this heterogeneity in social orienting may contribute to our comprehension of the mechanisms underlying autistic symptoms thereby improving our ability to intervene. Indeed, children on the autism spectrum who show higher levels of interest in social stimuli demonstrate reduced clinical symptoms and increased adaptive functioning. However, longitudinal studies examining the influence of social orienting on subsequent outcome are critically lacking. Here, we aim to explore the relationship between social interest at the age of 3 and changes in severity of autistic symptoms over the subsequent year, in 20 children with ASD and 20 age-matched typically developing (TD) children. A visual preference for social stimuli was measured using an eye-tracking task at baseline, consisting of a previously studied visual preference paradigm presenting biological and geometric motion side-by-side. The task was altered for the current study by alternating presentation side for each type of stimuli to keep visual perseveration from influencing participants’ first fixation location. Clinical data were collected both at baseline and 1 year later at follow-up. As a group, we observed reduced interest for biological motion (BIO-M) in children with ASD compared to TD children, corroborating previous findings. We also confirmed that a preference for BIO-M is associated with better adaptive functioning in preschoolers with ASD. Most importantly, our longitudinal results showed that a preference for BIO-M strongly predicted decreased severity of diagnostic symptoms. Participants who preferred social stimuli at the age of 3 showed drastic reductions in their severity level of autistic symptoms 1 year later, whereas participants who preferred geometric stimuli showed autistic symptoms that were unchanged or more severe after 1 year. As a whole, our results suggest that a preference for BIO-M may be key to understanding the behavioral phenotype of young children with ASD, and may represent a promising candidate behavior for predicting early developmental trajectories and outcome.

4. Large-scale functional network reorganization in 22q11.2 deletion syndrome revealed by modularity analysis

   Scariati, E., Schaer, M., Karahanoglu, I., Schneider, M., Richiardi, J., Debbané, M., Van De Ville, D., and Eliez, S.

   Cortex 2016
5. Developmental trajectories of executive functions in 22q11.2 deletion syndrome

   Maeder, J., Schneider, M., Bostelmann, M., Debbané, M., Glaser, B., Menghetti, S., Schaer, M., and Eliez, S.

   J Neurodev Disord 2016
6. An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome

   Váša, F., Griffa, A., Scariati, E., Schaer, M., Urben, S., Eliez, S., and Hagmann, P.

   Neuroimage Clin 2016
7. Abnormal spindle-like microcephaly-associated (ASPM) mutations strongly disrupt neocortical structure but spare the hippocampus and long-term memory

   Passemard, S., Verloes, A., Villemeur, T., Boespflug-Tanguy, O., Hernandez, K., Laurent, M., Isidor, B., Alberti, C., Pouvreau, N., Drunat, S., Gérard, B., El Ghouzzi, V., Gallego, J., Elmaleh-Bergès, M., Huttner, W. B., Eliez, S., Gressens, P., and Schaer, M.

   Cortex 2016

2015

1. Structural and functional connectivity in the default mode network in 22q11.2 deletion syndrome

   Padula, M. C., Schaer, M., Scariati, E., Schneider, M., Van De Ville, D., Debbané, M., and Eliez, S.

   J Neurodev Disord 2015
2. Sex differences in cortical volume and gyrification in autism

   Schaer, M., Kochalka, J., Padmanabhan, A., Supekar, K., and Menon, V.

   Mol Autism 2015

   Abstract URL PDF

   Background: Male predominance is a prominent feature of autism spectrum disorders (ASD), with a reported male to female ratio of 4:1. Because of the overwhelming focus on males, little is known about the neuroanatomical basis of sex differences in ASD. Investigations of sex differences with adequate sample sizes are critical for improving our understanding of the biological mechanisms underlying ASD in females. Methods: We leveraged the open-access autism brain imaging data exchange (ABIDE) dataset to obtain structural brain imaging data from 53 females with ASD, who were matched with equivalent samples of males with ASD, and their typically developing (TD) male and female peers. Brain images were processed with FreeSurfer to assess three key features of local cortical morphometry: volume, thickness, and gyrification. A whole-brain approach was used to identify significant effects of sex, diagnosis, and sex-by-diagnosis interaction, using a stringent threshold of p < 0.01 to control for false positives. Stability and power analyses were conducted to guide future research on sex differences in ASD. Results: We detected a main effect of sex in the bilateral superior temporal cortex, driven by greater cortical volume in females compared to males in both the ASD and TD groups. Sex-by-diagnosis interaction was detected in the gyrification of the ventromedial/orbitofrontal prefrontal cortex (vmPFC/OFC). Post-hoc analyses revealed that sex-by-diagnosis interaction was driven by reduced vmPFC/OFC gyrification in males with ASD, compared to females with ASD as well as TD males and females. Finally, stability analyses demonstrated a dramatic drop in the likelihood of observing significant clusters as the sample size decreased, suggesting that previous studies have been largely underpowered. For instance, with a sample of 30 females with ASD (total n = 120), a significant sex-by-diagnosis interaction was only detected in 50 % of the simulated subsamples. Conclusions: Our results demonstrate that some features of typical sex differences are preserved in the brain of individuals with ASD, while others are not. Sex differences in ASD are associated with cortical regions involved in language and social function, two domains of deficits in the disorder. Stability analyses provide novel quantitative insights into why smaller samples may have previously failed to detect sex differences.

2014

1. Congenital heart disease is associated with reduced cortical and hippocampal volume in patients with 22q11.2 deletion syndrome

   Fountain, D. M., Schaer, M., Mutlu, A. K., Schneider, M., Debbané, M., and Eliez, S.

   Cortex 2014
2. Identifying 22q11.2 deletion syndrome and psychosis using resting-state connectivity patterns

   Scariati, E., Schaer, M., Richiardi, J., Schneider, M., Debbané, M., Van De Ville, D., and Eliez, S.

   Brain Topogr 2014
3. Reduced brain cortical folding in schizophrenia revealed in two independent samples

   Nesvåg, R., Schaer, M., Haukvik, U. K., Westlye, L. T., Rimol, L. M., Lange, E. H., Hartberg, C. B., Ottet, M. C., Melle, I., Andreassen, O. A., Jönsson, E. G., Agartz, I., and Eliez, S.

   Schizophr Res 2014
4. Clinical and cognitive risk factors for psychotic symptoms in 22q11.2 deletion syndrome: a transversal and longitudinal approach

   Schneider, M., Schaer, M., Mutlu, A. K., Menghetti, S., Glaser, B., Debbané, M., and Eliez, S.

   Eur Child Adolesc Psychiatry 2014

2013

1. Decreased frontal gyrification correlates with altered connectivity in children with autism

   Schaer, M., Ottet, M. C., Scariati, E., Dukes, D., Franchini, M., Eliez, S., and Glaser, B.

   Front Hum Neurosci 2013

   Abstract URL PDF

   The structural correlates of functional dysconnectivity in autism spectrum disorders (ASD) have been seldom explored, despite the fact that altered functional connectivity is one of the most frequent neuropathological observations in the disorder. We analyzed cerebral morphometry and structural connectivity using multi-modal imaging for 11 children/adolescents with ASD and 11 matched controls. We estimated regional cortical and white matter volumes, as well as vertex-wise measures of cortical thickness and local Gyrification Index (lGI). Diffusion Tensor Images (DTI) were used to measure Fractional Anisotropy (FA) and tractography estimates of short- and long-range connectivity. We observed four clusters of lGI reduction in patients with ASD, three were located in the right inferior frontal region extending to the inferior parietal lobe, and one was in the right medial parieto-occipital region. Reduced volume was found in the anterior corpus callosum, along with fewer inter-hemispheric frontal streamlines. Despite the spatial correspondence of decreased gyrification and reduced long connectivity, we did not observe any significant relationship between the two. However, a positive correlation between lGI and local connectivity was present in all four clusters in patients with ASD. Reduced gyrification in the inferior fronto-parietal and posterior medial cortical regions lends support for early-disrupted cortical growth in both the mirror neuron system and midline structures responsible for social cognition. Early impaired neurodevelopment in these regions may represent an initial substrate for altered maturation in the cerebral networks that support complex social skills. We also demonstrate that gyrification changes are related to connectivity. This supports the idea that an imbalance between short- and long-range white matter tracts not only impairs the integration of information from multiple neural systems, but also alters the shape of the brain early on in autism.

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

   Woodward, S. H., Kuo, J. R., Schaer, M., Kaloupek, D. G., and Eliez, S.

   Neuroimage Clin 2013
3. Risk factors and the evolution of psychosis in 22q11.2 deletion syndrome: a longitudinal 2-site study

   Gothelf, D., Schneider, M., Green, T., Debbané, M., Frisch, A., Glaser, B., Zilkha, H., Schaer, M., Weizman, A., and Eliez, S.

   J Am Acad Child Adolesc Psychiatry 2013
4. Graph theory reveals dysconnected hubs in 22q11DS and altered nodal efficiency in patients with hallucinations

   Ottet, M. C., Schaer, M., Debbané, M., Cammoun, L., Thiran, J. P., and Eliez, S.

   Front Hum Neurosci 2013
5. Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment: neural markers of vulnerability?

   Kelly, P. A., Viding, E., Wallace, G. L., Schaer, M., De Brito, S. A., Robustelli, B., and McCrory, E. J.

   Biol Psychiatry 2013
6. Sex differences in thickness, and folding developments throughout the cortex

   Mutlu, A. K., Schneider, M., Debbané, M., Badoud, D., Eliez, S., and Schaer, M.

   Neuroimage 2013

   Abstract URL PDF

   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 30 years, 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.

7. Reduced fronto-temporal and limbic connectivity in the 22q11.2 deletion syndrome: vulnerability markers for developing schizophrenia?

   Ottet, M. C., Schaer, M., Cammoun, L., Schneider, M., Debbané, M., Thiran, J. P., and Eliez, S.

   PLoS One 2013

2012

1. Hippocampal volume reduction in chromosome 22q11.2 deletion syndrome (22q11.2DS): a longitudinal study of morphometry and symptomatology

   Flahault, A., Schaer, M., Ottet, M. C., Debbané, M., and Eliez, S.

   Psychiatry Res 2012
2. Cortical morphometry in narcolepsy with cataplexy

   Schaer, M., Poryazova, R., Schwartz, S., Bassetti, C. L., and Baumann, C. R.

   J Sleep Res 2012
3. How to measure cortical folding from MR images: a step-by-step tutorial to compute local gyrification index

   Schaer, M., Cuadra, M. B., Schmansky, N., Fischl, B., Thiran, J. P., and Eliez, S.

   J Vis Exp 2012
4. Degrees of separation: a quantitative neuroimaging meta-analysis investigating self-specificity and shared neural activation between self- and other-reflection

   Murray, R. J., Schaer, M., and Debbané, M.

   Neurosci Biobehav Rev 2012

2011

1. Catechol-O-methyltransferase Val158Met polymorphism moderates anterior cingulate volume in posttraumatic stress disorder

   Schulz-Heik, R. J., Schaer, M., Eliez, S., Hallmayer, J. F., Lin, X., Kaloupek, D. G., and Woodward, S. H.

   Biol Psychiatry 2011
2. Practical guidelines for managing patients with 22q11.2 deletion syndrome

   Bassett, A. S., McDonald-McGinn, D. M., Devriendt, K., Digilio, M. C., Goldenberg, P., Habel, A., Marino, B., Oskarsdottir, S., Philip, N., Sullivan, K., Swillen, A., Vorstman, J., Abadie, V., Allgrove, J., Amati, F., Baker, K., Baylis, A., Beaujard, M. P., Beemer, F., Boers, M., Bolton, P., Boot, E., Brigstocke, S., Burtey, S., Campbell, L., Chabloz, M., Chow, E., Clayton-Smith, J., Cubells, J., Debbané, M., Delrue, M. A., De Smedt, B., Duijff, S., Eicher, P., Emanuel, B., Evers, L., Flahault, A., Forsythe, A., Frebourg, T., Gennery, A., Goldmuntz, E., Gosling, A., Handler, S., Heine-Suñer, D., Hilmarsson, A., Hogan, A., Hordijk, R., Howley, S., Illingworth, E., Jackson, O., Joyce, H., Kawame, H., Kelly, R., Kemp, A., Kempf, L., Kimpen, J. L., Kirschner, R., Klaassen, P., Kumararatne, D., Lambert, M., Lima, K., Lindsay, E., Macerola, S., Malki, M. B., Marlin, S., Mascarenhas, M., Monks, S., Moran, V., Morrow, B., Moss, E., Murphy, C., Naqvi, N., Nielsen, B. W., Niklasson, L., Nordgarden, H., Oenema-Mostert, C. E., Ottet, M. C., Pasca, C., Pasquariello, P., Persson, C., Portnoi, M. F., Prasad, S., Rockers, K., Saitta, S., Scambler, P., Schaer, M., Schneider, M., Sell, D., Solot, C., Sommerlad, B., Unanue, N., Sundram, F., Van Aken, K., Amelsvoort, T., Molen, A. M., Widdershoven, J., and Zackai, E. H.

   J Pediatr 2011

2010

1. Regional cortical volumes and congenital heart disease: a MRI study in 22q11.2 deletion syndrome

   Schaer, M., Glaser, B., Ottet, M. C., Schneider, M., Bach Cuadra, M., Debbané, M., Thiran, J. P., and Eliez, S.

   J Neurodev Disord 2010

2009

1. Smaller global and regional cortical volume in combat-related posttraumatic stress disorder

   Woodward, S. H., Schaer, M., Kaloupek, D. G., Cediel, L., and Eliez, S.

   Arch Gen Psychiatry 2009
2. Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): a cross-sectional and longitudinal study

   Schaer, M., Debbané, M., Bach Cuadra, M., Ottet, M. C., Glaser, B., Thiran, J. P., and Eliez, S.

   Schizophr Res 2009
3. Hippocampal volume and declarative memory function in combat-related PTSD

   Woodward, S. H., Kaloupek, D. G., Grande, L. J., Stegman, W. K., Kutter, C. J., Leskin, L., Prestel, R., Schaer, M., Reiss, A. L., and Eliez, S.

   J Int Neuropsychol Soc 2009
4. Prefrontal plasticity and stress inoculation-induced resilience

   Katz, M., Liu, C., Schaer, M., Parker, K. J., Ottet, M. C., Epps, A., Buckmaster, C. L., Bammer, R., Moseley, M. E., Schatzberg, A. F., Eliez, S., and Lyons, D. M.

   Dev Neurosci 2009
5. Congenital heart disease affects local gyrification in 22q11.2 deletion syndrome

   Schaer, M., Glaser, B., Cuadra, M. B., Debbane, M., Thiran, J. P., and Eliez, S.

   Dev Med Child Neurol 2009

2008

1. Genes, brain development and psychiatric phenotypes in velo-cardio-facial syndrome

   Gothelf, D., Schaer, M., and Eliez, S.

   Dev Disabil Res Rev 2008
2. Right anterior cingulate cortical volume covaries with respiratory sinus arrhythmia magnitude in combat veterans

   Woodward, S. H., Kaloupek, D. G., Schaer, M., Martinez, C., and Eliez, S.

   J Rehabil Res Dev 2008
3. Cingulate gyral reductions are related to low executive functioning and psychotic symptoms in 22q 11.2 deletion syndrome

   Dufour, F., Schaer, M., Debbané, M., Farhoumand, R., Glaser, B., and Eliez, S.

   Neuropsychologia 2008
4. A surface-based approach to quantify local cortical gyrification

   Schaer, M., Cuadra, M. B., Tamarit, L., Lazeyras, F., Eliez, S., and Thiran, J. P.

   IEEE Trans Med Imaging 2008

   Abstract URL

   The high complexity of cortical convolutions in humans is very challenging both for engineers to measure and compare it, and for biologists and physicians to understand it. In this paper, we propose a surface-based method for the quantification of cortical gyrification. Our method uses accurate 3-D cortical reconstruction and computes local measurements of gyrification at thousands of points over the whole cortical surface. The potential of our method to identify and localize precisely gyral abnormalities is illustrated by a clinical study on a group of children affected by 22q11 Deletion Syndrome, compared to control individuals.

2007

1. Structural changes to the fusiform gyrus: a cerebral marker for social impairments in 22q11.2 deletion syndrome?

   Glaser, B., Schaer, M., Berney, S., Debbane, M., Vuilleumier, P., and Eliez, S.

   Schizophr Res 2007
2. From genes to brain: understanding brain development in neurogenetic disorders using neuroimaging techniques

   Schaer, M., and Eliez, S.

   Child Adolesc Psychiatr Clin N Am 2007

2006

1. Hippocampal volume reduction in 22q11.2 deletion syndrome

   Debbané, M., Schaer, M., Farhoumand, R., Glaser, B., and Eliez, S.

   Neuropsychologia 2006
2. Abnormal patterns of cortical gyrification in velo-cardio-facial syndrome (deletion 22q11.2): an MRI study

   Schaer, M., Schmitt, J. E., Glaser, B., Lazeyras, F., Delavelle, J., and Eliez, S.

   Psychiatry Res 2006
3. Decreased anterior cingulate volume in combat-related PTSD

   Woodward, S. H., Kaloupek, D. G., Streeter, C. C., Martinez, C., Schaer, M., and Eliez, S.

   Biol Psychiatry 2006