Funding

The ultimate goal of the project is to provide a screening and rehabilitation method for the early detection and treatment of developmental dyscalculia (DD), in the form of an entertaining, tablet-based gaming environment. DD is a common learning disability and severely impacts personal and professional development throughout the lifespan. Early diagnosis and interventions increase the possibilities for people with DD to live an independent and productive life. Children with DD have difficulties to map numbers’ representation into space (in contrast, typically developing children understanding of numerical concepts is facilitated by spatial mapping of numbers). We want to develop a tool which will use a gaming environment to evaluate and stimulate Space Number Association (SNA) in children. Kids will be stimulated with game-like SNA tasks and monitored with more general mathematical skills tasks. We will link the device with an online algorithm for on-line extraction of the responses that can compute and analyse each kid’s performance to track it as it changes over time. This project builds on two behavioural tasks I have established to implicitly assess SNA in children and infants. These paradigms can become a first-stage screening tool for individuals at high-risk for DD. We will further advance this method into a tool that allows easy, rapid and automatic testing of space-to-number processing in young children from any cultural and educational background, and in any context. The paradigms will be embedded in a gaming environment which is optimally engaging for the young users, facilitating the spontaneous participation in foundational numerical training targeted to the needs and specific numerical competences of each child. Moreover, we will further validate relationship between SNA and core numerical competence development, providing initial crucial steps for empirical validation of our method as an early screening tool for DD.

• Searching for sensitivity to stimulus statistics: Evolutionary mechanisms, development and critical periods underlying efficient neural coding

  PRIN 2022 (DD 104 del 02/02/22) – PNRR – M4 – C2 – INV 1.1 – PRIN – Titolo progetto [Searching for sensitivity to stimulus statistics: Evolutionary mechanisms, development and critical periods underlying efficient neural coding] – codice identificativo progetto [2022WX3FM5] – CUP [E53D23009020006] – fondo UNITN [40104485 - VALLORTIGARA PRIN 2022] – Finanziato dall’Unione europea – Next Generation EU.”

• The emergence of proto-arithmetic abilities with empty and non-empty sets.
  
  The ability to deal with numbers is fundamental in our modern society. From managing money to everyday calculations and estimations (e.g. the rest, discounts, etc.), numerical skills are continuously needed in everyday life. Previous evidence indicates that our arithmetic capacities are supported by an evolutionary relevant mechanism that is shared among human and non-human animals and that is present without exhaustive training. However, being good at math is not straightforward. Students around the world struggle with it more than with any other subject, such that around 32% do not reach the minimum knowledge required for their age. Relevant to the present proposal is the largely reported difficulty young children (and apparently not animals) experience in conceptualizing the number zero. We tackle this problem from its origins, by combining educational and experimental approaches in children and animal models with the overarching goal of capitalizing upon primitive capacities to understand and promote its learning. Specifically, we propose a series of experiments in 4 years-old children, chicks, and fish to explore -in parallel- how these species operate with zero and other numbers in proto-arithmetic operations that progressively require more abstract and symbolic representations. The final aim would be to inform educational strategies from an evidence-based approach. Therefore, the team also plans to develop ad-hoc digital educational tools using machine learning algorithms to effectively teach the properties of zero in preschool years.
  
  PRIN 2022 PNRR (DD 1409 del 14/09/22) – PNRR – M4 – C2 – INV1.1 – PRIN –Titolo progetto [The emergence of proto-arithmetic abilities with empty and non-empty sets] – codice identificativo progetto [P2022TKY7B] – CUP [E53D23019640001] – fondo UNITN [40104644 - VALLORTIGARA PRIN PNRR 2022] – Finanziato dall’Unione europea – Next Generation EU

The neurobiology of numerical cognition: searching for a molecular genetic signature in the zebrafish brain

Number-space associations in the brain Research in cognitive science has revealed that the temporal, spatial, and numerical features of a stimulus can interact with one another. An example is the tendency to map increasing numerical magnitudes with a left-to-right orientation. Numerical-spatial associations (NSA) are pervasive in human behaviour 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, mice 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. The project will be guided by a new hypothesis that links the direction of NSA to a differential role of the two sides of the brain to the perceived value (valence) of changes in magnitudes. The role of the experience (WP1) in the development of NSA will be investigated making use of early exposure to light in chicks’ embryos to modulate brain asymmetry, and 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 (WP2) 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 (WP3) 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 (WP4) 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.

What underlies the ability to count and where did it come from? One hypothesis is that our ability to accurately represent the number of objects in a set (numerosity), and to carry out numerical comparisons and simple arithmetic, developed from an evolutionarily conserved system for approximating numerical magnitude.

According to this hypothesis the ability to assess numerosities would have a conserved genetic and neural basis, and aspects of the neurobiology underlying ability to perform approximate numerical tasks would be conserved. However, although a wide range of species are able to estimate numerosities, only in primates has a neural mechanism homologous to humans' been demonstrated and the underlying cellular processes are unknown.

Thus, this project aims to test the broad hypothesis that the ability to represent numerosity has an evolutionarily conserved neural basis, and to identify the cell and molecular processes involved using multidisciplinary analysis in an evolutionarily distant vertebrate, the zebrafish.

The aim of the study is realize a high resolution three-dimensional atlas of the chick's brain (Gallus gallus) through the use of magnetic resonance. Once the atlas is made, we plan to study the pattern of brain activation during an early form of learning, the filial imprinting. Using functional magnetic resonance we can study the possible lateralization phenomena and the temporal and systemic dynamics of the activation of the cerebral areas involved in imprinting.

Portable EEG-based screening of social predispositions in newborns.

Predispositions to preferentially orient towards cues associated with social partners, such as face-like stimuli or biological and animate motion, appear to guide human social behavior from the onset of life and are typically impaired in children with autism-spectrum disorders (ASD). An early detector of social predispositions and their impairment in newborns might provide a valuable biomarker for ASD, an indicator of utmost relevance since infants with ASD greatly benefit from early behavioral intervention. This proposal builds on a study performed within my ERC grant in which, by designing an innovative oscillatory visual presentation of face-like patterns and perceptually equivalent controls, we identified an EEG-based index of face processing, present in each newborn tested and obtainable with less than 2 minutes of newborn’s visual attention. However, recording newborn’s EEG is currently possible only in laboratory settings, as no fully portable EEG system adapted for newborns exists in the market. The goal of this proposal is to design a portable, wireless EEG-based device that allows easy, rapid and automatic testing of face processing in newborns in any context, including their homes. This device is ground-breaking because it will combine the efficacy of our innovative experimental paradigm tailored to newborn’s restricted visual attention with a portable, low-power, wireless EEG device based on dry electrodes and an automatic algorithm that will extract on-line the EEG-based index of face processing. Its realization will enable the development of an early, objective and easy-to-test EEG-based biomarker on newborns at risk, potentially opening the way to large-scale screening protocols. Given the flexibility of the paradigm with respect to the content of the visual stimulation, this method might be used for research purposes to explore the neural bases of other perceptual and cognitive functions in newborns.

A project for early diagnoses of autism spectrum disorders.

Number-space association: A comparative, developmental and neurobiological approach
Abstract: Rudimental numerical abilities are widespread in the animal kingdom: similarities in non-symbolic numerical skills between humans and other animals suggest a shared "number sense".
A peculiar feature of numerical representation is its relation with space: numbers are represented by human adults along a horizontal left-right continuum, the "Mental Number Line". This was for long time considered a by-product of culture and education. Recently, though, evidence for similar effects was found in preverbal infants and in non-human animals, such as domestic chicks, suggesting a possible evolutionarily ancient origin of this phenomenon. The present project aims to investigate the origin of the number-space association (NSA) to understand its evolutionary and developmental origin, neural correlates and genetic basis.
We will investigate if the non-verbal NSA effects recently observed in domestic chicks can be found also in monkeys, zebrafish and mice, and how they develop in preverbal infants. This will clarify if this phenomenon is shared among distant species, if it is more generally limited to animals with laterally placed eyes and reduced interhemispheric connections or if it reflects the structural and developmental peculiarities of the avian visual system. This will be achieved using animal species with peculiar characteristics to fit our aim. For example, zebrafish will allow to test the generality of the spatial coding of numerosities in an animal model having a markedly different embryonic development than chicks (with regard to the presence of asymmetries in the environmental stimuli to the left and right visual pathways).
On the other hand, the study of human infants and monkeys will extend our observations to pre-verbal/non- verbal organisms that have frontally placed eyes and much stronger interhemispheric connections. 
Another aim of this project is to clarify the role of experience in the development of NSA. In humans the left-to right orientation of the NSA can be influenced by cultural factors (reading and writing). We will investigate the role of the experience in the development of the neural networks supporting NSA by studying its neural correlates in infants and children of different ages, with particular attention to the presence of interhemispheric differences. We will also study chicks that systematically experienced events interfering with the predisposition to process numbers from left to right (e.g. right-to-left sequences), using this model also to directly assess hemispheric specialization and the role of prenatal stimulation in its development.
We will also investigate the neural basis of the left-to-right oriented NSA, which is still poorly understood. To this aim the fNIRS studies in human infants and children will be directly compared to similar EEG investigations conducted in monkeys (which will provide also increased temporal resolution), assessing the development and evolution of hemispheric asymmetries in these phenomena. Complementary to that, the neural basis of NSA will also be studied in zebrafish with techniques that can reveal task-related brain activation at the single-cell activity level (e.g. immunohystochemical staining of Immediate Early Gene products), offering thus great spatial resolution.
Another important aim of this project is to investigate the role of NSA in the typical and atypical development of formal mathematic abilities. The innate number-space association is an important aspect of the number sense, and in children, the performance on number sense and space-related task correlates with the performance in arithmetical tasks. In order to identify early markers of the development of these functions, we will test if individual differences in the early neural correlates of NSA are predictive of later mathematical performance in children. Related to that, we shall also employ animal models to study the role of candidate genes, involved in human dyscalculia and in the development of cerebral lateralization, in the NSA effects. Dyscalculia affects 3-6% of the children. Kids with dyscalculia, although often endowed with normal perception, language and intelligence, show disproportionate difficulties in numerical elaboration and in arithmetic. In families with at least one dyscalculic child, the prevalence of dyscalculia in first-degree relatives is ten times higher than in the rest of the population. The genetic background of NSA effects will be investigated using zebrafish and mice mutant models of genes associated with human dyscalculia and with cerebral lateralization.

Neural bases of animacy detection, and their relevance to the typical and atypical development of a social brain.

An innovative screening protocol device for early identification of neonates at high-risk for Autism Spectrum Disorders.

This project has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 295517.

Predispositions for newly hatched/born vertebrates, including humans, to attend to and preferentially learn about conspecifics, are pervasive and can be of vital biological importance. Such predispositions are, however, very poorly understood. Studying them, and their physiological, genetic, molecular and neural bases, is crucial for an understanding of typical and atypical human development.

The aim of the project would be to study, in parallel, the neural bases of the biological predispositions to attend to motion and other visual characteristics (such as face or face-like stimuli) of living things in the newly-hatched domestic chick and in the human newborn.

In particular, we will develop a detailed animal model of vertebrate social predispositions using the domestic chick, relating this work closely to equivalent behavioural and neural measures in human newborns including those at risk of autism, for which there is no widely accepted animal model.

We aim to identify in chicks neural systems underlying known social predispositions; study their physiological, genetic and molecular bases; pursue behavioural parallels between chick and human predispositions; study brain structures activated in human newborns as they view social stimuli; by studying social attachment in chicks not expressing specific predispositions, develop a secure animal model of autism.