Periodic Reporting for period 1 - BrainTree (Evolution of neuroanatomical diversity: A phylogenetic comparative analysis across vertebrates using MRI.)
Berichtszeitraum: 2022-02-01 bis 2024-01-31
The study of brain evolution allows us to better understand the emergence of brain organisation, providing a unique perspective on the natural and pathological variability of the human brain – a major challenge for neuroscience. But comparative anatomy data are rare: Only a few species – mostly mice and humans – focus most research efforts, and building bridges between them is not trivial.
Project BrainTree addressed this by studying brain evolution across more than 150 species using neuroimaging and phylogenetic comparative methods, focusing on folding and mechanical morphogenesis – the emergence of complex shapes from physical instabilities triggered by growth. The project aimed to analyse neuroanatomical variation, test evolutionary models, and explore vertebrate brain evolution, shedding light on the emergence of brain organisation at multiple levels.
Grounded in open science and collaboration, BrainTree created a large open database of vertebrate brain MRI and histological data and a framework for distributed collaboration in comparative neuroscience. By studying the evolution and conservation of neuroanatomy, the project shed light on how brain size, surface area and folding evolved, how current diversity emerged and what the brains of the common ancestors of primates and mammals likely have looked like.
Project BrainTree addressed this by studying brain evolution across more than 150 species using neuroimaging and phylogenetic comparative methods, focusing on folding and mechanical morphogenesis – the emergence of complex shapes from physical instabilities triggered by growth. The project aimed to analyse neuroanatomical variation, test evolutionary models, and explore vertebrate brain evolution, shedding light on the emergence of brain organisation at multiple levels.
Grounded in open science and collaboration, BrainTree created a large open database of vertebrate brain MRI and histological data and a framework for distributed collaboration in comparative neuroscience. By studying the evolution and conservation of neuroanatomy, the project shed light on how brain size, surface area and folding evolved, how current diversity emerged and what the brains of the common ancestors of primates and mammals likely have looked like.
Work performed
We did a detailed study of vertebrate brain evolution using neuroimaging, histological data, and computational neuroanatomy methods, and creating collaborative platforms for neuroimaging. This included building a large open database of vertebrate brain MRI, with a focus on primates, and generating precise 3D brain reconstructions to extract measurements like brain volume, surface area, and folding. Using phylogenetic comparative methods, we tested evolutionary scenarios, estimated ancestral phenotypes, evolutionary changes, and multivariate relationships across brain structures. The project was a collaboration between the Group of Theoretical and Applied Neuroanatomy at Institut Pasteur, the National Natural History Museum in Paris, and the Institute of Biology at École Normale Supérieure.
Results
In this project, we have collected a large comparative dataset and studied neuroanatomical diversity across more than 150 species.
In the first part of the project, we studied the diversity and evolution of cerebellar folding across mammals which was published in eLife. We analysed histological data from 56 species, and created tools to study the geometry of cerebellar folia and to estimate the thickness of the molecular layer. We identified two distinct sets of phenotypes. The first set comprised "diverse" traits, such as body weight, brain weight, and the area and length of cerebellar and cerebral sections. These traits showed a huge variation across species, spanning multiple orders of magnitude in relation to body size. In contrast, the second set consisted of "stable" traits, including folial width and the molecular layer thickness, which showed minimal variation and changed only marginally with differences in brain size.
Phylogenetic comparative methods showed that the evolution of cerebellar and cerebral neuroanatomy across mammals follows a stabilising selection process, where phenotypes vary randomly and converge around one value. Ancestral phenotype estimations indicated that size and folding of the cerebrum and cerebellum increase and decrease concertedly through evolution. They confirmed that the common ancestor of mammals had a folded cerebrum and a correspondingly folded cerebellum, comparable to the brain of a Rock hyrax. Our results confirmed a strong correlation between the size of the cerebellum and the cerebrum, and revealed a disproportionately higher degree of folding of large cerebella compared to smaller ones. Furthermore, it showed a relationship between cerebellar fold width and molecular layer thickness. Across this large range of species, these patterns were remarkably consistent, hinting at a shared mechanism that governs the folding of the cerebrum and cerebellum in mammals that can be explained by buckling and where wavelength of folding depends on cortical thickness.
In the second phase of the project, we examined neuroanatomical variability across a wide range of primates. By collecting and analysing MRI data for 70 species – the largest sample to date – and incorporating endocast data, we studied neuroanatomical diversity in 105 primates. We created tools to segment the data and reconstruct precise 3D brain surfaces for all species, many of which have not been available before. We computed traits like cerebral volume, surface area, and folding metrics, and applied phylogenetic comparative methods to study evolutionary patterns. Results showed brain evolution in primates follows a Brownian motion model, where phenotypes vary randomly, with some branches (e.g. humans) showing brain volume increases, others (e.g. galagos) showing decreases, and mixed patterns elsewhere. The common primate ancestor, 74 million years ago, likely had a folded brain similar to an Aye-aye. Our findings highlight strong links between folding and brain volume and reveal conserved fold width across species, offering valuable insights into primate brain evolution, including humans.
Exploitation and dissemination
Two peer-reviewed articles have been published, with one featured in a press release, one submitted, and others are in progress. Additionally, four articles resulting from collaborations related to this project have been published. The results were shared through talks by the MSCA fellow at 8 conferences (4 international, 4 national) and several talks by the supervisor, as well as in a poster, a science festival, and on the project website.
We did a detailed study of vertebrate brain evolution using neuroimaging, histological data, and computational neuroanatomy methods, and creating collaborative platforms for neuroimaging. This included building a large open database of vertebrate brain MRI, with a focus on primates, and generating precise 3D brain reconstructions to extract measurements like brain volume, surface area, and folding. Using phylogenetic comparative methods, we tested evolutionary scenarios, estimated ancestral phenotypes, evolutionary changes, and multivariate relationships across brain structures. The project was a collaboration between the Group of Theoretical and Applied Neuroanatomy at Institut Pasteur, the National Natural History Museum in Paris, and the Institute of Biology at École Normale Supérieure.
Results
In this project, we have collected a large comparative dataset and studied neuroanatomical diversity across more than 150 species.
In the first part of the project, we studied the diversity and evolution of cerebellar folding across mammals which was published in eLife. We analysed histological data from 56 species, and created tools to study the geometry of cerebellar folia and to estimate the thickness of the molecular layer. We identified two distinct sets of phenotypes. The first set comprised "diverse" traits, such as body weight, brain weight, and the area and length of cerebellar and cerebral sections. These traits showed a huge variation across species, spanning multiple orders of magnitude in relation to body size. In contrast, the second set consisted of "stable" traits, including folial width and the molecular layer thickness, which showed minimal variation and changed only marginally with differences in brain size.
Phylogenetic comparative methods showed that the evolution of cerebellar and cerebral neuroanatomy across mammals follows a stabilising selection process, where phenotypes vary randomly and converge around one value. Ancestral phenotype estimations indicated that size and folding of the cerebrum and cerebellum increase and decrease concertedly through evolution. They confirmed that the common ancestor of mammals had a folded cerebrum and a correspondingly folded cerebellum, comparable to the brain of a Rock hyrax. Our results confirmed a strong correlation between the size of the cerebellum and the cerebrum, and revealed a disproportionately higher degree of folding of large cerebella compared to smaller ones. Furthermore, it showed a relationship between cerebellar fold width and molecular layer thickness. Across this large range of species, these patterns were remarkably consistent, hinting at a shared mechanism that governs the folding of the cerebrum and cerebellum in mammals that can be explained by buckling and where wavelength of folding depends on cortical thickness.
In the second phase of the project, we examined neuroanatomical variability across a wide range of primates. By collecting and analysing MRI data for 70 species – the largest sample to date – and incorporating endocast data, we studied neuroanatomical diversity in 105 primates. We created tools to segment the data and reconstruct precise 3D brain surfaces for all species, many of which have not been available before. We computed traits like cerebral volume, surface area, and folding metrics, and applied phylogenetic comparative methods to study evolutionary patterns. Results showed brain evolution in primates follows a Brownian motion model, where phenotypes vary randomly, with some branches (e.g. humans) showing brain volume increases, others (e.g. galagos) showing decreases, and mixed patterns elsewhere. The common primate ancestor, 74 million years ago, likely had a folded brain similar to an Aye-aye. Our findings highlight strong links between folding and brain volume and reveal conserved fold width across species, offering valuable insights into primate brain evolution, including humans.
Exploitation and dissemination
Two peer-reviewed articles have been published, with one featured in a press release, one submitted, and others are in progress. Additionally, four articles resulting from collaborations related to this project have been published. The results were shared through talks by the MSCA fellow at 8 conferences (4 international, 4 national) and several talks by the supervisor, as well as in a poster, a science festival, and on the project website.
This project significantly expanded the landscape of neuroanatomical variation by adding numerous species previously unavailable for study, offering an unparalleled view of natural brain diversity. Through global collaborations, we created a large open collection of vertebrate brain MRI and histological data.
We also developed tools to foster collaborative research, including BrainBox (https://brainbox.pasteur.fr(öffnet in neuem Fenster)) and MicroDraw (https://microdraw.pasteur.fr(öffnet in neuem Fenster)) enabling visualisation and global collaboration on MRI and high-resolution histology. These open-source platforms facilitate data sharing and distributed collaboration, promoting data re-use and reproducible research. The tools and methods developed within this project are available open source, allowing other researchers to use them for the analysis of other unusual datasets.
Our findings provided deeper insights into the structure and evolution of cerebral and cerebellar anatomy across mammals, suggesting a shared mechanism underlying cerebrum and cerebellum folding driven by buckling, with fold width determined by cortical thickness, as a fundamental principle shared by this large group of species.
By integrating an evolutionary approach, we tested the role of mechanical constraints across different scales and different brain structures reflecting different aspects of brain organisation, including changes in size and folding. By examining the role of a poorly studied factor – mechanical morphogenesis – the results of this work could profoundly change the current understanding of the processes underlying the development and evolution of the organisation of the brain and open multiple new scientific avenues
We also developed tools to foster collaborative research, including BrainBox (https://brainbox.pasteur.fr(öffnet in neuem Fenster)) and MicroDraw (https://microdraw.pasteur.fr(öffnet in neuem Fenster)) enabling visualisation and global collaboration on MRI and high-resolution histology. These open-source platforms facilitate data sharing and distributed collaboration, promoting data re-use and reproducible research. The tools and methods developed within this project are available open source, allowing other researchers to use them for the analysis of other unusual datasets.
Our findings provided deeper insights into the structure and evolution of cerebral and cerebellar anatomy across mammals, suggesting a shared mechanism underlying cerebrum and cerebellum folding driven by buckling, with fold width determined by cortical thickness, as a fundamental principle shared by this large group of species.
By integrating an evolutionary approach, we tested the role of mechanical constraints across different scales and different brain structures reflecting different aspects of brain organisation, including changes in size and folding. By examining the role of a poorly studied factor – mechanical morphogenesis – the results of this work could profoundly change the current understanding of the processes underlying the development and evolution of the organisation of the brain and open multiple new scientific avenues