Regional GABA levels modulate abnormal resting-state network functional connectivity and cognitive impairment in...

Area of Science:

• Neuroscience
• Neurology
• Radiology

Background:

• Cognitive impairment in multiple sclerosis (MS) is linked to altered brain network functional connectivity and neurometabolite levels.
• The precise neurological mechanisms connecting neurometabolites, functional connectivity, and cognitive deficits in MS remain incompletely understood.

Purpose of the Study:

• To investigate the relationship between gamma-aminobutyric acid (GABA) and glutamate concentrations, functional connectivity, and cognitive function in relapsing-remitting MS (RRMS).
• To explore the mediating role of neurometabolite levels in the association between network connectivity and cognitive decline in RRMS.

Main Methods:

• Utilized magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (rs-fMRI) in 29 RRMS patients and 34 healthy controls.
• Measured GABA and glutamate in the posterior cingulate cortex, medial prefrontal cortex, and left hippocampus.
• Assessed inter-network functional connectivity within cognitive-related networks and employed neuropsychological tests for cognitive evaluation.

Main Results:

• RRMS patients exhibited significantly lower GABA and glutamate concentrations compared to controls.
• Aberrant functional connectivity in cognitive-related networks was observed in RRMS patients, correlating with cognitive decline.
• Mediation analysis revealed that reduced hippocampal GABA levels in RRMS patients mediated the relationship between default mode network connectivity and verbal memory deficits.

Conclusions:

• GABAergic system abnormalities play a crucial role in regulating network dysconnectivity and altered functional connectivity in RRMS.
• These findings highlight potential therapeutic targets for cognitive dysfunction in multiple sclerosis.
• The study provides novel insights into the neurobiological underpinnings of cognitive impairment in MS.