Progression of brain functional connectivity and frontal cognitive dysfunction in ALS

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons.
• Frontal cognitive dysfunction is a common non-motor symptom in ALS.
• Understanding the neural underpinnings of cognitive changes is crucial for comprehensive ALS management.

Purpose of the Study:

• To investigate the longitudinal progression of resting-state functional connectivity (rs-FC) changes in ALS patients.
• To examine the relationship between rs-FC alterations and frontal cognitive deficits in ALS.
• To identify potential neuroimaging markers for extra-motor progression in ALS.

Main Methods:

• A multicentre, observational, longitudinal study involving 25 ALS patients.
• Baseline and six-month follow-up assessments included 3D T1-weighted MRI, resting-state functional MRI (rs-fMRI), and the Test of Attentional Performance (TAP).
• Independent component analysis and seed-based approaches were used to analyze rs-FC changes in brain networks, particularly involving the frontal lobe and middle frontal gyrus (MFG).

Main Results:

• ALS patients exhibited progressive increases in rs-FC within frontostriatal and frontoparietal networks over six months.
• Worse baseline performance on divided attention and category fluency tasks correlated with increased rs-FC in specific frontal regions (left MFG, left superior frontal gyrus).
• Seed-based analysis revealed decreased rs-FC between the right MFG and frontoparietal regions in ALS patients compared to controls.

Conclusions:

• rs-FC changes in ALS patients progress over time and are associated with frontal-executive dysfunction.
• The middle frontal gyrus (MFG) may be a key region in the frontoparietal functional breakdown characteristic of ALS.
• These findings suggest rs-FC alterations could serve as novel biomarkers for monitoring the extra-motor progression of ALS.