Modelling Joubert Syndrome: a personalized multiscale approach to investigate brain activity

Motivation: Hypoplastic cerebellar vermis is the main hallmark of Joubert syndrome (JS), thus pipelines commonly applied to healthy controls must be personalized to capture the specific pathological features. Goal(s): Here, a multiscale approach is developed to simulate personalized brain activity in JS. Approach: MRI volumetric data is used to evaluate cerebellar changes in JS, which are then embedded in microscale models of cerebellar neuronal circuits, whose output is used to build mesoscale models (mean field) reflecting JS pathophysiology. Results: The inclusion of reduced volume and number of cells in the microscale model of JS impacts on microscale and mesoscale neuronal activity. Impact: Personalized pipelines for diseases, such as Joubert Syndrome, can help to investigate pathophysiology and brain activity alterations. The use of a multiscale approach can be the key to investigate brain dynamic alterations at multiple levels of complexity.