Advancing functional dysconnectivity and atrophy in progressive supranuclear palsy.

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Progressive supranuclear palsy syndrome (PSP-S) involves neurodegeneration across multiple brain regions.
• The progression of network dysfunction and its relation to atrophy and clinical decline in PSP-S remain unclear.

Purpose of the Study:

• To investigate the longitudinal progression of network dysfunction, atrophy, and clinical decline in PSP-S.
• To correlate neuroimaging findings with clinical severity and progression in PSP-S patients.

Main Methods:

• Structural MRI and task-free functional MRI (tf-fMRI) were used to assess 12 PSP-S patients and 20 controls at baseline and 6 months.
• Voxel-based morphometry (VBM) analyzed structural atrophy, while functional connectivity (FC) was examined in a rostral midbrain tegmentum (rMT)-anchored network.

Main Results:

• Baseline VBM showed atrophy in subcortex, brainstem, prefrontal cortex (PFC), and parietal cortex in PSP-S patients.
• Baseline tf-fMRI revealed FC deficits in PSP-S within rMT network hubs, particularly in prefrontal-paralimbic and subcortical-brainstem modules.
• Longitudinally, PSP-S patients exhibited declining intermodular FC between subcortical-brainstem and parietal modules, alongside progressive atrophy in midbrain, pallidum, and posterior frontal cortex.

Conclusions:

• PSP-S progression may involve an earlier subcortical-anterior cortical disease process followed by later subcortical-posterior cortical changes.
• Neuroimaging markers (VBM and FC) can track disease stages and heterogeneous clinical progression in PSP-S, aiding disease monitoring.