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Number-space associations in the brain

Periodic Reporting for period 1 - SPANUMBRA (Number-space associations in the brain)

Reporting period: 2019-11-01 to 2021-04-30

It is well-known that the numerical features of a stimulus can interact with the spatial features. An example is the tendency to map increasing numerical magnitudes with a left-to-right orientation. These numerical-spatial associations (NSA) are pervasive in human behavior and have relevance to health (e.g. dyscalculia is thought to be related to improper understanding of the so-called «mental number line»). NSA have been shown to occur in human newborns and in non-human animals for non-symbolic numerousness. SPANUMBRA aims to investigate NSA in different animal models (domestic chicks and zebrafish) and in human neonates and infants to provide a comprehensive and comparative perspective on the developmental, neural and genetic origins of this phenomenon. In particular, the role of the experience in the development of NSA will be investigated making use of controlled-rearing experiments in which newly-hatched chicks will be exposed to correlated and anti-correlated discrete and continuous magnitudes. Development of NSA will be also studied in human neonates and infants before, during, and after the exposure to culture-specific NSA associations (numbers organized in spatially oriented layouts) to investigate the role of culture in shaping/reinforcing NSA. The study of the neural basis of the NSA will combine neurobiological techniques (immediate early gene expression in chicks and zebrafish), and non-invasive methods (EEG and fNIRS in human neonates). The genetic bases of NSA will be investigated using transgenic lines of zebrafish and mice, in order to understand the role of some genes implicated in the development of lateralization and in dyscalculia.
In the first 18 months of the project we started experiments on controlled-reared chicks using behavioural methods and early gene expression. We hope to complete them and have some results by the Autumn. Meanwhile, we published a behavioural paper on chicks showing that numerical magnitude, rather than individual bias, explains spatial numerical association in these newborn animals (Rugani et al (2020) eLife) and another paper investigating sex differences in spatial-numerical cognition in chicks (Lemaire et al. (2020) Learning & Behavior). With zebrafish we were able to complete a first series of two main studies involving habituation/dishabituation experiments followed by qPCR of early gene expression and in situ hybridation. These studies were very successful and conducted to the identification of a small area of the pallium associated with number processing (we already published a paper on this, see Messina et al. (2020) Sci. Rep.) and another one has been submitted to a major journal and is currently available on bioRxiv (Messina et al. (2020) bioRxiv). Meanwhile, our colleagues at QMU started to develop transgenic lines for candidate genes for dyscalculia, and we hope to be able to test these zebrafish very soon. We also tested fish at different ages in numerical tasks and submitted a paper on this. We also investigated in zebrafish the distribution of pallial-expressed genes of relevance to numerical and other cognition, and found striking asymmetries (we published a paper on this: Messina et al. (2020) Eur. J. Neurosci.). We also progressed well in developing standardized techniques for presentation of numerical stimuli with control of continuous physical variables, and a paper on this was accepted by a major methodological journal (Zanon et al. (2021) Behavior Research Methods, in press). Studies with human babies and infants were unfortunately blocked because of the pandemics prevented access to the hospital labs; we were nonetheless able to set all things with respect to ethics requirements and prepared all set ups and scripts; we hope to start soon this part when things will be better in our Country. Finally, we published some major reviews on topics related to brain asymmetries and numerical and spatio-numerical cognition in animals (Miletto-Petrazzini et al. (2020) Front. Neuroanat.; Bortot et al. (2020) Biochem. Biophys. Res. Comm.; Lorenzi et al. (2021) Front. Psychol.).
I believe the work we did on numerical representation in zebrafish is a sort of breakthrough, because now we know of at least one area which is specifically involved in number cognition in the pallium of these animals. This would open the door to circuitry and genetic analyses at a level that would have no precedent in more traditional models. We hope to get soon further results about connectivity with others regions as well as patterns of asymmetry of response, particularly in gene expression that will ensure further progress in our understanding of number and number/space associations.
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