A dive into brain diversity: How common brain spaces can break the silos in neuroscience
One of the least appreciated aspects of brain organization is its diversity across species. Although anatomists have been mapping out brains of non-human species since the start of the 20th century, the laborious and invasive nature of this work means that we still have very little understanding of how our human brain differs from that of other species.
This has important implications for translational neuroscience. We use so-called model species, such as mice, rats, marmosets, and macaques to inform us about aspects of our own brain. However, research on human and non-human species is often done in very different traditions by separate groups of researchers.
Animal brain versus human brain
This leads to many confusions about how the anatomy of species translates (Van Heukelum et al., 2020, TINS) and even about terminology to describe cognitive tasks used in different species (Laubach et al., 2018, eNeuro). It has been argued that this is one of the reasons why many clinical trials fail (Hay et al., 2014, Nat Biotechnol). It is also one of the main causes of different types of neuroscientists ending up in silos, without communication with researchers outside their direct discipline.
One way to address this problem is to formalize the similarities and differences in results obtained using different methods and in different species.
Therefore, this Challenge proposes to build multi-model, multi-species maps of the brain and to create formal translational mappings between these different maps. By building brain maps across modalities and species using the same approaches and using the same terminologies, it will be possible to describe them all within a common abstract space. This, in turn, will allow direct, quantitative comparisons of results (cf. Mars et al., 2021, Annu Rev Neurosci).
Main goals of this challenge
- Understand principles of brain organization
- Allow application of knowledge obtained in model species to our understanding of the human brain
- Improve the translation between preclinical and clinical neuroscience
- Reduce the number of animals used in research by better tailoring models and research questions
Rogier Mars
Comparative neuroimaging
Christian Beckmann
Statistical imaging neuroscience
Simon Fisher
Genetics
Clyde Francks
Imaging genomics
Joanes Grandjean
Mouse neuroimaging
Judith Homberg
Translational neuroscience
Max Hinne
Bayesian statistics and machine learning
Serotonin and beyond
The European Training Network Serotonin & Beyond, coordinated by Judith Homberg, aims to dissect how changes in serotonin levels in early brain development affects vulnerability to major neuropsychiatric disorders, including autism, ADHD and depression. To this end parallel rat and human studies are conducted. We focus on the effect of maternal serotonergic genotype on the development of brain and behaviour in offspring. Complementary rat and human studies allow us to investigate the mechanisms underlying the developmental effects and consequences for transdiagnostic phenotypes in high detail in animals, and to validate the translational impact of the results in humans.
Contact: Judith.Homberg@radboudumc.nl
Developing techniques for cross-species neuroimaging
A key problem in comparative neuroscience is that we have to compare the organization of brains that differ vastly in size and morphology. Registering brains together in the way that is done for different human subjects is therefore impractical. To be able to quantitatively compare brain organization across species we have developed the so-called ‘common space’ approach.
By describing brains in terms of an abstract features space, such as common white matter tracts or homologous genes, it becomes possible to describe the brains using the same vocabulary. We have used this approach extensively to compare the macaque monkey and human brain, identifying unexpected homologies and also describing areas in the human brain that are fundamentally different in organization to that of any macaque brain region—indicating the limit of the translational paradigm. More recent students have extending this approach, comparing the human brain to that of the chimpanzee and gorilla great apes, as well as monkeys and rodents.
Contacts: joanes.grandjean@donders.ru.nl; rogier.mars@donders.ru.nl; max.hinne@donders.ru.nl
Comparing mouse and human brain connectivity
Left-right asymmetry is an important organizing feature of the healthy human brain for functions including language, motor control and attention. Altered brain asymmetry has been associated with variation in human cognitive abilities, and with psychiatric disorders such as autism and schizophrenia.
In this project we will study the adult mouse brain using spatial transcriptomics, to characterize mouse brain asymmetry at the molecular and cellular diversity levels, in wild type and knockout mice for genes implicated in human brain asymmetry. We will complement these studies with structural and functional MRI of these mice, and behavioural analysis. We will also work with mouse early embryos to study the developmental origins of brain asymmetry, and how it may be affected in relevant knockout lines.
Contacts:joanes.grandjean@donders.ru.nl, rogier.mars@donders.ru.nl, max.hinne@donders.ru.nl
Neurogenetics of brain asymmetry in mice
Left-right asymmetry is an important organizing feature of the healthy human brain for functions including language, motor control and attention. Altered brain asymmetry has been associated with variation in human cognitive abilities, and with psychiatric disorders such as autism and schizophrenia.
In this project we will study the adult mouse brain using spatial transcriptomics, to characterize mouse brain asymmetry at the molecular and cellular diversity levels, in wild type and knockout mice for genes implicated in human brain asymmetry. We will complement these studies with structural and functional MRI of these mice, and behavioural analysis. We will also work with mouse early embryos to study the developmental origins of brain asymmetry, and how it may be affected in relevant knockout lines.