Project

Trisomie 21; syndrome de Williams; hippocampus; Williams syndrome; Down syndrome; mémoire spatiale; navigation

Lead
Le syndrome de Down (Trisomie 21 ou T21) et le syndrome de Williams (SW) sont des maladies génétiques caractérisées par un retard mental et une diminution des capacités de traitement des informations visuospatiales. Toutefois, les capacités spatiales nécessaires pour naviguer dans le monde réel n’ont pas fait l’objet d’études comparées chez les personnes atteintes de T21 ou de SW. Ce projet a pour but de pallier à ce manque de connaissance.
Lay summary
Nore cerveau a plusieurs manières de représenter l’espace. Si nous sommes statiques, l’espace est représenté de manière égocentrique, en relation à notre propre corps : cet objet se trouve à droite devant moi. Alors que si nous nous déplaçons, l’espace est représenté de manière allocentrique, la position d’un objet est codée en relation avec les autres objets constituant l’environnement, indépendamment de notre propre corps. Dans une série d’expériences en environnement réel, nous étudierons les capacités de représentations spatiales de personnes atteintes de T21 et de SW. Les connaissances acquises nous permettront de mieux caractériser les capacités cognitives de personnes ayant des anomalies génétiques, et de mieux comprendre comment le cerveau humain contribue à la représentation spatiale de notre environnement. Ce projet relève de la recherche fondamentale. Toutefois, la compréhension des capacités de représentations spatiales chez les personnes atteintes de T21 et de SW pourrait conduire au développement de stratégies d’apprentissage permettant une plus grande autonomie.

Direct link to Lay Summary

Last update: 06.06.2016

Number	Title	Start	Funding scheme

Down syndrome (DS) and Williams syndrome (WS) are neurodevelopmental disorders with distinct genetic origins. Persons with these syndromes have cognitive deficits generically described as mild to moderate intellectual disability. However, over the last 20 years a concerted effort to compare the intellectual abilities of persons with DS and WS has led to the understanding that distinct etiologies yield distinct cognitive profiles. Nonetheless, the spatial abilities of these two populations have not yet been fully defined. Whereas a number of studies have investigated various aspects of spatial cognition, especially visuospatial processing, in DS and WS individuals, there has been no experiment appropriately designed to specifically assess basic real-world allocentric spatial capacities, which normally depend on the proper function of the hippocampus.The reasons for characterizing allocentric spatial memory processes in DS and WS are manifold: allocentric spatial memories are critical for the construction of cognitive maps, which are essential for developing independence and autonomy in individuals with intellectual disability; allocentric spatial memories are a fundamental component of episodic memory, and thus may serve as a proxy for assessing episodic memory function, especially in individuals with impaired language function; and finally, although allocentric spatial memory is one of the hallmark cognitive processes studied in mouse models of WS and DS, its impairment in humans with WS and DS has not been unequivocally demonstrated.Here, we propose to characterize the fundamental egocentric and allocentric spatial capacities of individuals with Down syndrome (DS), individuals with Williams syndrome (WS), and mental age-matched typically-developing (TD) children in controlled real-world environments.In Specific Aim 1, we will test the influence of spatial resolution on the allocentric and egocentric spatial memory abilities of DS, WS and TD individuals. Following our recent findings (1), we predict that about 50% of DS individuals will exhibit basic allocentric spatial capacities, which allow them to define locations with a low spatial resolution based on their topological relations to distal environmental cues, whereas 50% will not. We also predict that the performance of most DS individuals will be impaired on tasks requiring high spatial resolution capacities. In contrast, since WS individuals have severe visuospatial deficits, we predict that they will be impaired on all allocentric tasks integrating visual information, irrespective of spatial resolution. Individuals with DS and WS will perform relatively better in egocentric spatial tasks.In Specific Aim 2, we will test the ability of DS, WS and TD individuals to use self-generated motion information to build egocentric and allocentric representations of space in absence of vision. We hypothesize that, in absence of visual information, WS individuals will be able to form both egocentric and allocentric representations of space. Preserved ability to use self-generated motion information to represent space in an allocentric manner in WS will indicate that the impairments observed in other spatial tasks are most likely due to the reliance on corrupted dorsal visual stream input, and not the result of abnormal hippocampal processing. We predict that DS individuals will perform relatively well in tasks requiring them to use self-generated motion information to encode space in an egocentric manner. In contrast, we predict that whereas the DS individuals who are capable of forming an allocentric representation with vision in Experiment 1 will be able to build an allocentric spatial representation in absence of visual information, DS individuals who cannot create an allocentric representation with vision will be incapable of creating an allocentric representation in absence of visual information, thus suggesting specific hippocampal impairment.In Specific Aim 3, we will test DS and WS individuals with a number of neuropsychological exams that will allow us to identify measures that may correlate with our egocentric and allocentric spatial memory tasks, thus identifying clinical tasks for predicting allocentric processing deficits and, accordingly, hippocampal impairments.