Visual pathway abnormalities and self-organisation of the visual system

• Applicant: Professor Dr. Michael Hoffmann
• Subject Area: Ophthalmology
• Term: since 2009
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 149341228

Congenital malformations of the optic chiasm cause large scale abnormal input to the visual cortex. They therefore provide a valuable key to understand the framework guiding human visual pathway development and plasticity for the benefit of basic neuroscience and clinical applications. In the work leading up to this project we identified the visual cortex as a site of critical importance (a) for plastic mechanisms to make abnormal input available for visual function and (b) for action and failure of visual maturation. Remarkably, a potential cortical MRI-biomarker for such amblyopia-like processes appears to be generalizable beyond chiasma abnormalities, as indicated by our companion research on achromatopsia in an independent DFG-project. Based on these foundations, the proposed project aims to decipher how developmental mechanisms operate in the human visual brain at the level of brain function, connectivity, and anatomy. For this purpose, we will apply an interdisciplinary approach of ophthalmology, psychophysics, highest-standard anatomical/diffusion-weighted/functional MRI (a/d/fMRI) and artificial-intelligence based neuro-computations (deep-learning). Specifically, we will investigate (1) reorganisation of top-down attentional modulation with 7T fMRI, (2) intra-cortical connectivity and fine-structure via 7T a/dMRI, (3) altered visual development via deep-learning based analyses of MRI-brain-anatomies for individualized diagnostics. To make a significant, neuro-scientifically and clinically meaningful contribution to the understanding of visual pathway developments in congenital vision disorders, we will extend our investigations beyond our previous target group (chiasma abnormalities) by integrating groups with congenital cone-dysfunction (achromatopsia) and early blindness. This integration of our related, but previously independent research activities, paves the way for a generalization of our insights that will significantly increase the impact of our research. This is further supported by the use of highest-standard a/d/fMRI that is possible due to our proven expertise, our strong collaborations with leaders in the field, and the recent extension of the local infra-structure by the novel 7T connectome scanner (Siemens 7T Terra.X Impulse Edition). It is expected that this integrated approach of functional and structural analyses in congenital visual pathway disorders will provide significant insights into neural development and reorganisation that will have a lasting impact on our view of visual system plasticity and ultimately on clinical applications. Specifically, we aim to set a general precedent for the MRI-based identification of changes of intra-cortical and cortico-cortical connectivity, and of visual cortex maturation, including amblyopia correlates, that will spur the development of novel diagnostics and therapeutic approaches.

• DFG Programme: Research Grants