PROJECT: JTC2021: UnscrAMBLY

Understanding brain circuit dysfunction in amblyopia using large-scale multimodal recordings in a new visuomotor task applied to animal models and patients

Abstract

We aim to establish the role of predictive processing in neurodevelopmental disorders, specifically in one of the most studied context, amblyopia. We use a new visuomotor feedback task across high-visual-acuity preclinical species - cats -, rodents, and humans during brain-wide activity readout via best-available methods (functional ultrasound imaging reaching 4 cm depth, mesoscale two-photon imaging, hdEEG) to 1) identify brain regions involved in visuomotor prediction in normal subjects, 2) determine the effect of amblyopia on prediction-related activity patterns, 3) develop functional network models and use longitudinal study design to infer which brain regions and associated brain functions are restored or remain perturbed after amblyopia treatment, 4) validate results via optogenetic perturbation experiments in mice, 5) provide an EEG-based biomarker with high discriminative power across normal vision and different stages of amblyopia, 6) contribute the community with the comparative etiology of one of the best modelled neurodevelopmental disorders. Our results may demonstrate the discriminative power of a prediction feedback probing visuomotor task between amblyopic subjects who exhibit disrupted visuomotor function after having their acuity fully restored and controls. To elucidate the causes of this unmet medical need, we link brain-wide functional network activity to neurodevelopment in a behaving animal model that faithfully recapitulates human visual functions.

Keywords

Imaging techniques, Behavioural methodologies, Amblyopia, Patient cohorts, Animal studies, cross-species, multimodal, deep-brain

Call topic

Neurodevelopmental Disorders

Proposed runtime

n/a - n/a

Project team

Dániel Hillier (Coordinator)
Hungary (NKFI)
Maria-Magdolna Ercsey-Ravasz
Romania (UEFISCDI)
Koen Vervaeke
Norway (RCN)
Alan Urban
Belgium (FWO)
Zoltán Zsolt Nagy
Hungary (own funds)