Synchronization and variability imbalance underlie cognitive impairment in primary-progressive multiple sclerosis

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Primary-progressive multiple sclerosis (PP-MS) is characterized by progressive neurological decline.
• Cognitive deficits are common in PP-MS, impacting various domains.
• The underlying neural mechanisms, including functional connectivity and variability, are not fully understood.

Purpose of the Study:

• To investigate functional connectivity and variability in brain networks associated with cognitive deficits in PP-MS.
• To explore the impact of cortical lesions (CLs) on these brain network alterations.
• To examine alterations across multiple frequency bands.

Main Methods:

• Analysis of resting-state functional connectivity and signal variability (BOLD amplitude standard deviation).
• Comparison between 25 PP-MS patients and 20 healthy controls.
• Assessment across different frequency bands within resting-state networks (RSNs).
• Correlation analysis with cortical lesion volume.

Main Results:

• PP-MS patients exhibited widespread cognitive deterioration, particularly in visuo-spatial and executive functions.
• Cognitively impaired patients showed increased neural signal variability and reduced synchronicity in functionally related networks.
• Hyper-synchronicity was observed in functionally segregated networks.
• Cortical lesion volume was higher in impaired patients and correlated with altered functional connectivity and variability.

Conclusions:

• Functional reorganization, characterized by altered synchronicity patterns across large-scale brain networks, underlies cognitive dysfunction in PP-MS.
• Cortical lesions may play a significant role in the observed abnormalities in functional connectivity and neural variability.
• These findings provide novel insights into the neurobiological basis of cognitive impairment in PP-MS.