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Summary

Parkinson disease (PD) involves widespread functional connectivity (FC) disruptions beyond primary brain pathology. These network-level changes, particularly in sensorimotor, thalamic, and cerebellar areas, may explain diverse clinical symptoms.

Keywords:
Parkinson diseasefMRIfunctional connectivitynetworks

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Area of Science:

  • Neuroscience
  • Neurology
  • Systems Neuroscience

Background:

  • Parkinson disease (PD) pathology, primarily synucleinopathy, starts in the brainstem and spreads rostrally.
  • Subcortical pathology alone does not fully explain the diverse clinical symptoms observed in PD patients.
  • Resting-state functional connectivity (FC) offers a method to investigate widespread network dysfunction in PD.

Purpose of the Study:

  • To examine resting-state functional connectivity (FC) differences between non-demented Parkinson disease (PD) patients and healthy controls.
  • To identify specific brain networks and regions most affected by FC alterations in PD.
  • To explore the relationship between FC disruptions and clinical manifestations in PD.

Main Methods:

  • A large, single-site study measured FC in 107 non-demented PD patients (OFF medications) and 46 healthy controls.
  • Comprehensive sampling included cortical, subcortical, and cerebellar regions.
  • Novel statistical approaches analyzed group differences across the entire connectome, at the network-level, and in specific regions, with split-half replication for robustness.

Main Results:

  • Group differences in FC exhibited a distinct "block-wise" pattern of network-to-network effects.
  • The most significant FC differences were observed in sensorimotor, thalamic, and cerebellar networks, with less pronounced effects in striatal regions.
  • FC disruptions showed correlations with behavioral measures, suggesting a link to clinical symptoms.

Conclusions:

  • Functional connectivity (FC) deficits in Parkinson disease (PD) represent a concerted breakdown of network interactions, extending beyond focal pathology.
  • These network-level phenomena, particularly in sensorimotor, thalamic, and cerebellar circuits, are crucial for understanding PD's clinical spectrum.
  • FC analysis provides valuable insights into the distributed nature of brain dysfunction in PD.