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Article ; Online: Diversity and evolution of cerebellar folding in mammals

Katja Heuer / Nicolas Traut / Alexandra Allison de Sousa / Sofie Louise Valk / Julien Clavel / Roberto Toro

eLife, Vol

2023 Volume 12

Abstract: The process of brain folding is thought to play an important role in the development and organisation of the cerebrum and the cerebellum. The study of cerebellar folding is challenging due to the small size and abundance of its folia. In consequence, ... ...

Abstract	The process of brain folding is thought to play an important role in the development and organisation of the cerebrum and the cerebellum. The study of cerebellar folding is challenging due to the small size and abundance of its folia. In consequence, little is known about its anatomical diversity and evolution. We constituted an open collection of histological data from 56 mammalian species and manually segmented the cerebrum and the cerebellum. We developed methods to measure the geometry of cerebellar folia and to estimate the thickness of the molecular layer. We used phylogenetic comparative methods to study the diversity and evolution of cerebellar folding and its relationship with the anatomy of the cerebrum. Our results show that the evolution of cerebellar and cerebral anatomy follows a stabilising selection process. We observed two groups of phenotypes changing concertedly through evolution: a group of ‘diverse’ phenotypes – varying over several orders of magnitude together with body size, and a group of ‘stable’ phenotypes varying over less than 1 order of magnitude across species. Our analyses confirmed the strong correlation between cerebral and cerebellar volumes across species, and showed in addition that large cerebella are disproportionately more folded than smaller ones. Compared with the extreme variations in cerebellar surface area, folial anatomy and molecular layer thickness varied only slightly, showing a much smaller increase in the larger cerebella. We discuss how these findings could provide new insights into the diversity and evolution of cerebellar folding, the mechanisms of cerebellar and cerebral folding, and their potential influence on the organisation of the brain across species.
Keywords	folding ; cerebellum ; evolution ; histology ; mammals ; phylogenetic comparative methods ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	612
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: FIIND

Roberto Toro / Rembrandt Bakker / Thierry Delzescaux / Alan Evans / Paul Tiesinga

Research Ideas and Outcomes, Vol 4, Iss , Pp 1-

Ferret Interactive Integrated Neurodevelopment Atlas

2018 Volume 29

Abstract: The first days after birth in ferrets provide a privileged view of the development of a complex mammalian brain. Unlike mice, ferrets develop a rich pattern of deep neocortical folds and cortico- cortical connections. Unlike humans and other primates, ... ...

Abstract	The first days after birth in ferrets provide a privileged view of the development of a complex mammalian brain. Unlike mice, ferrets develop a rich pattern of deep neocortical folds and cortico- cortical connections. Unlike humans and other primates, whose brains are well differentiated and folded at birth, ferrets are born with a very immature and completely smooth neocortex: folds, neocortical regionalisation and cortico-cortical connectivity develop in ferrets during the first postnatal days. After a period of fast neocortical expansion, during which brain volume increases by up to a factor of 4 in 2 weeks, the ferret brain reaches its adult volume at about 6 weeks of age. Ferrets could thus become a major animal model to investigate the neurobiological correlates of the phenomena observed in human neuroimaging. Many of these phenomena, such as the relationship between brain folding, cortico-cortical connectivity and neocortical regionalisation cannot be investigated in mice, but could be investigated in ferrets. Our aim is to provide the research community with a detailed description of the development of a complex brain, necessary to better understand the nature of human neuroimaging data, create models of brain development, or analyse the relationship between multiple spatial scales. We have already started a project to constitute an open, collaborative atlas of ferret brain development, integrating multi-modal and multi-scale data. We have acquired data for 28 ferrets (4 animals per time point from P0 to adults), using high-resolution MRI and diffusion tensor imaging (DTI). We have developed an open-source pipeline to segment and produce – online – 3D reconstructions of brain MRI data. We propose to process the brains of 16 of our specimens (from P0 to P16) using high-throughput 3D histology, staining for cytoarchitectonic landmarks, neuronal progenitors and neurogenesis. This would allow us to relate the MRI data that we have already acquired with multi-dimensional cell-scale information. Brains will be sectioned at 25 μm, stained, scanned at 0.25 μm of resolution, and processed for real-time multi-scale visualisation. We will extend our current web-platform to integrate an interactive multi-scale visualisation of the data. Using our combined expertise in computational neuroanatomy, multi-modal neuroimaging, neuroinformatics, and the development of inter-species atlases, we propose to build an open-source web platform to allow the collaborative, online, creation of atlases of the development of the ferret brain. The web platform will allow researchers to access and visualise interactively the MRI and histology data. It will also allow researchers to create collaborative, human curated, 3D segmentations of brain structures, as well as vectorial atlases. Our work will provide a first integrated atlas of ferret brain development, and the basis for an open platform for the creation of collaborative multi-modal, multi-scale, multi-species atlases.
Keywords	Neuroanatomy ; Brain Development ; Ferret ; Open S ; Science ; Q
Subject code	004
Language	English
Publishing date	2018-03-01T00:00:00Z
Publisher	Pensoft Publishers
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Open Neuroimaging Laboratory

Katja Heuer / Satrajit Ghosh / Amy Robinson Sterling / Roberto Toro

Research Ideas and Outcomes, Vol 2, Iss , Pp 1-

2016 Volume 7

Keywords	Neuroimaging ; Collaboration ; Open Science ; Co-e ; Science ; Q
Language	English
Publishing date	2016-05-01T00:00:00Z
Publisher	Pensoft Publishers
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phelan-McDermid syndrome

Katy Phelan / Luigi Boccuto / Craig M. Powell / Tobias M. Boeckers / Conny van Ravenswaaij-Arts / R. Curtis Rogers / Carlo Sala / Chiara Verpelli / Audrey Thurm / William E. Bennett / Christopher J. Winrow / Sheldon R. Garrison / Roberto Toro / Thomas Bourgeron

Orphanet Journal of Rare Diseases, Vol 17, Iss 1, Pp 1-

a classification system after 30 years of experience

2022 Volume 4

Abstract: Abstract Phelan-McDermid syndrome (PMS) was initially called the 22q13 deletion syndrome based on its etiology as a deletion of the distal long arm of chromosome 22. These included terminal and interstitial deletions, as well as other structural ... ...

Abstract	Abstract Phelan-McDermid syndrome (PMS) was initially called the 22q13 deletion syndrome based on its etiology as a deletion of the distal long arm of chromosome 22. These included terminal and interstitial deletions, as well as other structural rearrangements. Later, pathogenetic variants and deletions of the SHANK3 gene were found to result in a phenotype consistent with PMS. The association between SHANK3 and PMS led investigators to consider disruption/deletion of SHANK3 to be a prerequisite for diagnosing PMS. This narrow definition of PMS based on the involvement of SHANK3 has the adverse effect of causing patients with interstitial deletions of chromosome 22 to “lose” their diagnosis. It also results in underreporting of individuals with interstitial deletions of 22q13 that preserve SHANK3. To reduce the confusion for families, clinicians, researchers, and pharma, a simple classification for PMS has been devised. PMS and will be further classified as PMS-SHANK3 related or PMS-SHANK3 unrelated. PMS can still be used as a general term, but this classification system is inclusive. It allows researchers, regulatory agencies, and other stakeholders to define SHANK3 alterations or interstitial deletions not affecting the SHANK3 coding region.
Keywords	Phelan-McDermid syndrome ; PMS ; SHANK3 ; 22q13 deletion ; Medicine ; R
Subject code	572
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The meaning of significant mean group differences for biomarker discovery.

Eva Loth / Jumana Ahmad / Chris Chatham / Beatriz López / Ben Carter / Daisy Crawley / Bethany Oakley / Hannah Hayward / Jennifer Cooke / Antonia San José Cáceres / Danilo Bzdok / Emily Jones / Tony Charman / Christian Beckmann / Thomas Bourgeron / Roberto Toro / Jan Buitelaar / Declan Murphy / Guillaume Dumas

PLoS Computational Biology, Vol 17, Iss 11, p e

2021 Volume 1009477

Abstract: Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of tailored therapies. Nevertheless, the prevailing statistical ... ...

Abstract	Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of tailored therapies. Nevertheless, the prevailing statistical approach is still the mean group comparison between "cases" and "controls," which tends to ignore within-group variability. In this educational article, we used empirical data simulations to investigate how effect size, sample size, and the shape of distributions impact the interpretation of mean group differences for biomarker discovery. We then applied these statistical criteria to evaluate biomarker discovery in one area of psychiatric research-autism research. Across the most influential areas of autism research, effect size estimates ranged from small (d = 0.21, anatomical structure) to medium (d = 0.36 electrophysiology, d = 0.5, eye-tracking) to large (d = 1.1 theory of mind). We show that in normal distributions, this translates to approximately 45% to 63% of cases performing within 1 standard deviation (SD) of the typical range, i.e., they do not have a deficit/atypicality in a statistical sense. For a measure to have diagnostic utility as defined by 80% sensitivity and 80% specificity, Cohen's d of 1.66 is required, with still 40% of cases falling within 1 SD. However, in both normal and nonnormal distributions, 1 (skewness) or 2 (platykurtic, bimodal) biologically plausible subgroups may exist despite small or even nonsignificant mean group differences. This conclusion drastically contrasts the way mean group differences are frequently reported. Over 95% of studies omitted the "on average" when summarising their findings in their abstracts ("autistic people have deficits in X"), which can be misleading as it implies that the group-level difference applies to all individuals in that group. We outline practical approaches and steps for researchers to explore mean group comparisons for the discovery of stratification biomarkers.
Keywords	Biology (General) ; QH301-705.5
Subject code	310
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The meaning of significant mean group differences for biomarker discovery

PLoS Computational Biology, Vol 17, Iss

2021 Volume 11

Abstract	Over the past decade, biomarker discovery has become a key goal in psychiatry to aid in the more reliable diagnosis and prognosis of heterogeneous psychiatric conditions and the development of tailored therapies. Nevertheless, the prevailing statistical approach is still the mean group comparison between “cases” and “controls,” which tends to ignore within-group variability. In this educational article, we used empirical data simulations to investigate how effect size, sample size, and the shape of distributions impact the interpretation of mean group differences for biomarker discovery. We then applied these statistical criteria to evaluate biomarker discovery in one area of psychiatric research—autism research. Across the most influential areas of autism research, effect size estimates ranged from small (d = 0.21, anatomical structure) to medium (d = 0.36 electrophysiology, d = 0.5, eye-tracking) to large (d = 1.1 theory of mind). We show that in normal distributions, this translates to approximately 45% to 63% of cases performing within 1 standard deviation (SD) of the typical range, i.e., they do not have a deficit/atypicality in a statistical sense. For a measure to have diagnostic utility as defined by 80% sensitivity and 80% specificity, Cohen’s d of 1.66 is required, with still 40% of cases falling within 1 SD. However, in both normal and nonnormal distributions, 1 (skewness) or 2 (platykurtic, bimodal) biologically plausible subgroups may exist despite small or even nonsignificant mean group differences. This conclusion drastically contrasts the way mean group differences are frequently reported. Over 95% of studies omitted the “on average” when summarising their findings in their abstracts (“autistic people have deficits in X”), which can be misleading as it implies that the group-level difference applies to all individuals in that group. We outline practical approaches and steps for researchers to explore mean group comparisons for the discovery of stratification biomarkers. Author summary Currently, ...
Keywords	Biology (General) ; QH301-705.5
Subject code	310
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genome wide association study of incomplete hippocampal inversion in adolescents.

Claire Cury / Marzia Antonella Scelsi / Roberto Toro / Vincent Frouin / Eric Artiges / Antoine Grigis / Andreas Heinz / Hervé Lemaître / Jean-Luc Martinot / Jean-Baptiste Poline / Michael N Smolka / Henrik Walter / Gunter Schumann / Andre Altmann / Olivier Colliot / IMAGEN Consortium

PLoS ONE, Vol 15, Iss 1, p e

2020 Volume 0227355

Abstract: Incomplete hippocampal inversion (IHI), also called hippocampal malrotation, is an atypical presentation of the hippocampus present in about 20% of healthy individuals. Here we conducted the first genome-wide association study (GWAS) in IHI to elucidate ... ...

Abstract	Incomplete hippocampal inversion (IHI), also called hippocampal malrotation, is an atypical presentation of the hippocampus present in about 20% of healthy individuals. Here we conducted the first genome-wide association study (GWAS) in IHI to elucidate the genetic underpinnings that may contribute to the incomplete inversion during brain development. A total of 1381 subjects contributed to the discovery cohort obtained from the IMAGEN database. The incidence rate of IHI was 26.1%. Loci with P<1e-5 were followed up in a validation cohort comprising 161 subjects from the PING study. Summary statistics from the discovery cohort were used to compute IHI heritability as well as genetic correlations with other traits. A locus on 18q11.2 (rs9952569; OR = 1.999; Z = 5.502; P = 3.755e-8) showed a significant association with the presence of IHI. A functional annotation of the locus implicated genes AQP4 and KCTD1. However, neither this locus nor the other 16 suggestive loci reached a significant p-value in the validation cohort. The h2 estimate was 0.54 (sd: 0.30) and was significant (Z = 1.8; P = 0.036). The top three genetic correlations of IHI were with traits representing either intelligence or education attainment and reached nominal P< = 0.013.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Social and non-social autism symptoms and trait domains are genetically dissociable

Varun Warrier / Roberto Toro / Hyejung Won / Claire S. Leblond / Freddy Cliquet / Richard Delorme / Ward De Witte / Janita Bralten / Bhismadev Chakrabarti / Anders D. Børglum / Jakob Grove / Geert Poelmans / David A. Hinds / Thomas Bourgeron / Simon Baron-Cohen

Communications Biology, Vol 2, Iss 1, Pp 1-

2019 Volume 13

Abstract: Varun Warrier et al. report a genome-wide association study of systemising, a non-social trait associated with autism. They find 3 loci associated with systemising and show that this trait has no significant genetic correlations to social phenotypic ... ...

Abstract	Varun Warrier et al. report a genome-wide association study of systemising, a non-social trait associated with autism. They find 3 loci associated with systemising and show that this trait has no significant genetic correlations to social phenotypic measures, demonstrating that the social and non-social aspects of autism are genetically distinct.
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A collaborative resource platform for non-human primate neuroimaging

Adam Messinger / Nikoloz Sirmpilatze / Katja Heuer / Kep Kee Loh / Rogier B. Mars / Julien Sein / Ting Xu / Daniel Glen / Benjamin Jung / Jakob Seidlitz / Paul Taylor / Roberto Toro / Eduardo A. Garza-Villarreal / Caleb Sponheim / Xindi Wang / R. Austin Benn / Bastien Cagna / Rakshit Dadarwal / Henry C. Evrard /

Pamela Garcia-Saldivar / Steven Giavasis / Renée Hartig / Claude Lepage / Cirong Liu / Piotr Majka / Hugo Merchant / Michael P. Milham / Marcello G.P. Rosa / Jordy Tasserie / Lynn Uhrig / Daniel S. Margulies / P. Christiaan Klink

NeuroImage, Vol 226, Iss , Pp 117519- (2021)

2021

Abstract: Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to ... ...

Abstract	Neuroimaging non-human primates (NHPs) is a growing, yet highly specialized field of neuroscience. Resources that were primarily developed for human neuroimaging often need to be significantly adapted for use with NHPs or other animals, which has led to an abundance of custom, in-house solutions. In recent years, the global NHP neuroimaging community has made significant efforts to transform the field towards more open and collaborative practices. Here we present the PRIMatE Resource Exchange (PRIME-RE), a new collaborative online platform for NHP neuroimaging. PRIME-RE is a dynamic community-driven hub for the exchange of practical knowledge, specialized analytical tools, and open data repositories, specifically related to NHP neuroimaging. PRIME-RE caters to both researchers and developers who are either new to the field, looking to stay abreast of the latest developments, or seeking to collaboratively advance the field .
Keywords	Open science ; Resource sharing ; Toolbox ; Pipeline ; Structural ; Functional ; Neurosciences. Biological psychiatry. Neuropsychiatry ; RC321-571
Subject code	020
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Resting state networks' corticotopy

Salma Mesmoudi / Vincent Perlbarg / David Rudrauf / Arnaud Messe / Basile Pinsard / Dominique Hasboun / Claudia Cioli / Guillaume Marrelec / Roberto Toro / Habib Benali / Yves Burnod

PLoS ONE, Vol 8, Iss 7, p e

the dual intertwined rings architecture.

2013 Volume 67444

Abstract: How does the brain integrate multiple sources of information to support normal sensorimotor and cognitive functions? To investigate this question we present an overall brain architecture (called "the dual intertwined rings architecture") that relates the ...

Abstract	How does the brain integrate multiple sources of information to support normal sensorimotor and cognitive functions? To investigate this question we present an overall brain architecture (called "the dual intertwined rings architecture") that relates the functional specialization of cortical networks to their spatial distribution over the cerebral cortex (or "corticotopy"). Recent results suggest that the resting state networks (RSNs) are organized into two large families: 1) a sensorimotor family that includes visual, somatic, and auditory areas and 2) a large association family that comprises parietal, temporal, and frontal regions and also includes the default mode network. We used two large databases of resting state fMRI data, from which we extracted 32 robust RSNs. We estimated: (1) the RSN functional roles by using a projection of the results on task based networks (TBNs) as referenced in large databases of fMRI activation studies; and (2) relationship of the RSNs with the Brodmann Areas. In both classifications, the 32 RSNs are organized into a remarkable architecture of two intertwined rings per hemisphere and so four rings linked by homotopic connections. The first ring forms a continuous ensemble and includes visual, somatic, and auditory cortices, with interspersed bimodal cortices (auditory-visual, visual-somatic and auditory-somatic, abbreviated as VSA ring). The second ring integrates distant parietal, temporal and frontal regions (PTF ring) through a network of association fiber tracts which closes the ring anatomically and ensures a functional continuity within the ring. The PTF ring relates association cortices specialized in attention, language and working memory, to the networks involved in motivation and biological regulation and rhythms. This "dual intertwined architecture" suggests a dual integrative process: the VSA ring performs fast real-time multimodal integration of sensorimotor information whereas the PTF ring performs multi-temporal integration (i.e., relates past, present, and ...
Keywords	Medicine ; R ; Science ; Q
Subject code	720
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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