Unravelling brain connectopathy with cross-species fMRI

Speaker: Alessandro Gozzi, PhD

Senior Scientist, Functional Neuroimaging Laboratory, Italian Institute of Technology, Rovereto, Italy

Bio: Alessandro Gozzi, PhD, is a senior scientist and group leader at the Italian Institute of Technology, in Rovereto, Italy. The Gozzi lab focuses on the development and application of advanced MRI methods to study the mammalian brain organization at the macroscale. A major goal of Gozzi’s research is to unravel the elusive neural basis of brain-wide functional coupling, and to identify the physiological underpinnings of brain connectopathy in developmental disorders such as autism. The Gozzi lab addresses these questions via the combination of cutting-edge functional MRI mapping with genetic and neural manipulations in the living mouse brain. This approach has laid the foundations for a new field of research in which large-scale neuroimaging readouts are used as probe of network activity and dysfunction across species.

Talk abstract: Aberrant functional connectivity as measured with resting state fMRI (rsfMRI) is a hallmark feature of brain connectopathy in psychiatric, developmental and neurological disorders. However, fundamental questions as to the origin and significance of rsfMRI-based dysconnectivity remain open. Why is functional connectivity so heterogeneous across patient cohorts, and what are the implications of this heterogeneity? And can we back-translate specific rsfMRI dysconnectivity signatures into physiologically interpretable events?

To address these questions, my laboratory has developed methods to map rsfMRI connectivity in the mouse, a physiologically accessible species where genetic determinants and neuronal activity can be causally manipulated with great specificity. In my lecture I will summarize some key results from this recent line of inquiry. I will highlight substantial correspondences in the spatio-temporal organization of mouse and human rsfMRI networks, supporting the translational relevance of this approach. I will show how this approach can help understand the significance of connectional heterogeneity in autism, and reconcile seemingly unrelated pathological domains into a unifying multi-scale framework. I will finally show how causal perturbational approaches can be used to deconstruct the fundamental elements of rsfMRI coupling, challenging long-held assumptions regarding the relationship between rsfMRI connectivity and its underlying axonal correlates. These examples outline a novel research platform that is poised to shed light on the basis and determinants of human brain connectopathy.