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Default mode network modifications in Fabry disease: A resting-state fMRI study with structural correlations.

Sirio Cocozza1, Giuseppe Pontillo1, Mario Quarantelli2

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Summary

Default Mode Network (DMN) alterations in Fabry Disease (FD) correlate with white matter damage and cognitive deficits. These widespread functional and microstructural changes indicate significant brain involvement beyond major cerebrovascular events in FD patients.

Keywords:
default mode networkfabry diseaseresting-state fMRItract-based spatial statistics

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Area of Science:

  • Neuroscience
  • Radiology
  • Genetics

Background:

  • Fabry Disease (FD) is a rare genetic disorder with potential neurological complications.
  • Cerebral involvement in FD is recognized, but the extent of Default Mode Network (DMN) alterations and their relationship with microstructural changes is not fully understood.

Purpose of the Study:

  • To investigate Default Mode Network (DMN) modifications in patients with classical Fabry Disease (FD).
  • To explore correlations between DMN alterations, structural brain changes (white matter damage), and neuropsychological performance in FD.

Main Methods:

  • Resting-State functional MRI (fMRI) was used to analyze DMN functional connectivity (FC) in 32 FD patients and 35 healthy controls (HC).
  • Voxel-Based Morphometry (VBM) and Tract-Based Spatial Statistics (TBSS) were employed to assess structural brain modifications.
  • Correlations between FC, white matter (WM) damage, and cognitive scores (e.g., Corsi block-tapping test) were analyzed.

Main Results:

  • FD patients exhibited increased DMN functional connectivity in both supratentorial and infratentorial regions.
  • These connectivity changes were partially correlated with widespread white matter (WM) damage observed in FD patients.
  • No significant gray matter volume differences were detected between FD patients and HC.
  • Connectivity between the right inferior frontal gyrus and precuneus correlated significantly with Corsi block-tapping test performance.

Conclusions:

  • Widespread DMN changes are present in FD patients.
  • These DMN alterations are associated with white matter damage and cognitive performance deficits.
  • The findings highlight diffuse microstructural and functional brain changes in FD, extending beyond major cerebrovascular events.