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Testing computational mechanisms for cognitive differences in humans ASD populations


About This PhD Project

Project Description

Project Code: 2020-SIDB-08

Classically, phenomenological clinical observations have been the starting point for attempts to stratify ASDs and to establish biological mechanisms. This PhD project will take a new approach, beginning with computations underlying core cognitive functions and developing new clinical tests that will generate quantitative insights into underlying mechanisms. The promise of this approach is that clinical tests rooted in mechanistic predictions developed from a biological understanding of brain circuits will have a high signal to noise ratio for detection of changes in cognitive function. By establishing if this is the case, the project will contribute to strategies for effective stratification, deep phenotyping and translation of findings between laboratory and clinical science.

The project will apply state-of-the-art virtual reality approaches to test predicted differences in higher order cognitive function resulting from altered information processing in the hippocampus, entorhinal cortex and their upstream inputs. The clinical tests developed will enable quantification of specific components of computations that underlie processes in humans that are collectively referred to as ‘scene construction’, or the process of mentally generating and maintaining a complex and coherent scene or event. Individuals with ASD have deficits in scene construction and theories of scene construction provide a unifying framework for mechanistic investigations. The clinical tests developed will be derived directly from virtual reality-based assays we have previously developed for rodent experiments. These assays provide new approaches for quantifying components of computations underlying scene construction, including roles of sensory input, internally generated signals and memory.

The project will progress from translation of virtual-reality tasks to a clinical setting through to investigation of patient populations. The first year of the project will build on ongoing work using analogues of rodent virtual reality tasks to investigation of spatial cognition in healthy human populations. The second year will focus on evaluation of patient populations. The third year will either explore the effect of interventions, or applications of EEG and fMRI to further evaluation of cognitive processes during the tasks. In parallel, new theoretical models will be developed to fit the clinical data and be used as a basis for making predictions about patient phenotypes. The project will involve the student testing patients who have been identified through existing cohorts. Therefore, this studentship would be particularly appropriate for applicants with a psychology degree (all training for the computational and modelling components would be provided), or those with a background in computational methods and modelling (clinical training will be provided).

References

1. Behrens, Timothy E. J., Timothy H. Muller, James C. R. Whittington, Shirley Mark, Alon B. Baram, Kimberly L. Stachenfeld, and Zeb Kurth-Nelson. 2018. “What Is a Cognitive Map? Organizing Knowledge for Flexible Behavior.” Neuron 100 (2): 490–509.

2. Hassabis, D., Maguire, E.A., 2007. Deconstructing episodic memory with construction. Trends Cogn. Sci. 11, 299–306.

3. Lind, S.E., Williams, D.M., Bowler, D.M., Peel, A., 2014. Episodic memory and episodic future thinking impairments in high-functioning autism spectrum disorder: An underlying difficulty with scene construction or self-projection? Neuropsychology 28, 55–67.

4. Tennant, S.A., Fischer, L., Garden, D.L.F., Gerlei, K.Z., Martinez-Gonzalez, C., McClure, C., Wood, E.R., Nolan, M.F., 2018. Stellate Cells in the Medial Entorhinal Cortex Are Required for Spatial Learning. Cell Rep. 22, 1313–1324.

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