Disrupted Energy Landscape in Individuals with Mild Cognitive Impairment: Insights from Network Control Theory

Area of Science:

• Neuroscience
• Systems Biology
• Medical Imaging

Background:

• Mild cognitive impairment (MCI) is an early stage of cognitive decline characterized by brain structural and functional disruptions.
• Understanding the interplay between brain structure and function is crucial for developing effective interventions for MCI.
• Network Control Theory (NCT) offers a multi-modal approach to analyze brain energetic landscapes by integrating functional activity and structural connectivity.

Purpose of the Study:

• To investigate the differences in the brain's energetic landscape between individuals with MCI and healthy controls (HC).
• To explore the relationship between brain transition energy (TE), entropy, and neurodegenerative markers (amyloid-beta and tau) in MCI.

Main Methods:

• Functional MRI (fMRI) and PET imaging were used in 55 MCI patients and 499 HC.
• K-means clustering identified recurring brain activity states from fMRI data.
• Network Control Theory (NCT) calculated transition energy (TE) between states. Entropy, amyloid-beta (Aβ), and tau deposition were measured. Linear models compared TE and entropy between groups and assessed associations with Aβ and tau.

Main Results:

• MCI patients exhibited lower transition energy (TE) in the limbic network compared to HC (adjusted p=0.028).
• Global entropy was significantly decreased in MCI patients (p=7.29e-7).
• A positive association was found between TE and entropy in the frontoparietal network (p=7.03e-3), and increased global Aβ correlated with higher global entropy in MCI (p=0.041).

Conclusions:

• Lower limbic network TE in MCI may reflect neurodegeneration or compensatory functional upregulation.
• Altered brain energetic landscapes, characterized by reduced TE and entropy, are evident in early cognitive impairment.
• Further research including Alzheimer's disease (AD) patients is needed to fully characterize energetic landscape changes across cognitive decline stages.