Stepwise Functional Brain Architecture Correlates with Atrophy in Progressive Supranuclear Palsy

Area of Science:

• Neuroscience
• Network Science
• Medical Imaging

Background:

• Stepwise functional connectivity (SFC) analyzes brain couplings at increasing topological distances.
• Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) is a neurodegenerative disease with poorly understood network effects.

Purpose of the Study:

• To investigate if stepwise functional connectivity architecture from the disease epicenter shapes brain atrophy in PSP-RS.
• To test the hypothesis of network-based pathology propagation in PSP-RS.

Main Methods:

• Applied SFC analysis to 36 PSP-RS patients and 44 healthy controls using 3-T MRI.
• Defined the disease epicenter in the left midbrain tegmental region based on postmortem-confirmed PSP pathology.
• Correlated SFC architecture from the epicenter with brain atrophy distribution.

Main Results:

• PSP-RS patients exhibited decreased SFC between the midbrain epicenter and striatal, cerebellar, and sensorimotor regions.
• A significant correlation (r=0.38, P<0.001) was found between midbrain link-step distance and brain volumes in PSP-RS patients.
• The left midbrain tegmental region was identified as the disease epicenter.

Conclusions:

• Brain architectural topology, assessed by SFC from the disease epicenter, significantly shapes atrophy patterns in PSP-RS.
• Findings support a network-based propagation model for this primary tauopathy.
• SFC provides insights into functional network rearrangements in PSP-RS.