Primary Brain Calcification (PBC) is a rare neurodegenerative disorder defined by bilateral calcifications predominantly within the basal ganglia, which may also extend to other cerebral and cerebellar regions. Clinically, PBC manifests with striking heterogeneity, including movement disorders (Parkinsonism, ataxia, dystonia, chorea, and episodic dyskinesia), as well as psychiatric (psychosis, anxiety, depression), cognitive, and other neurological symptoms (such as headache and vertigo).

The project stems from a cohort of 50 genetically confirmed PBC patients and 67 healthy volunteers, age- and sex- matched, recruited at the University Hospital of Padua, who underwent cognitive and motor evaluation with validated scales. Controls had no neurological or psychiatric history. All participants previously completed a multi-modal MRI protocol: T1-weighted, rs-fMRI, multi-shell diffusion MRI, ASL, QSM. Additional PBC patients will be recruited and undergo the same MRI and clinical protocol.

Study  – Voxel-wise characterization of white-matter microstructural alterations and their functional correlates in PBC

Starting from the diffusion-derived maps already available, the primary aim will be to perform a voxel-wise analysis to identify and characterize spatial patterns of white-matter microstructural alterations in patients with PBC compared with healthy controls, extending previous findings based on advanced diffusion MRI.

If compatible with the project timeline, resting-state fMRI data will also be analyzed to investigate whether brain regions connected through white-matter pathways showing evidence of microstructural damage also exhibit altered functional connectivity. This analysis will provide a first assessment of the relationship between structural white-matter abnormalities and functional network disruption in PBC.