Chronic hypercortisolism disrupts the principal functional gradient in Cushing's disease: A multi-scale connectomics...

Area of Science:

• Neuroscience
• Endocrinology
• Genetics

Background:

• Cushing's disease (CD) involves cortisol excess, impacting brain function and causing cognitive/affective disorders.
• The brain's functional connectome may underlie these neurological symptoms in CD.

Purpose of the Study:

• To investigate how chronic hypercortisolism in CD affects the brain's principal functional gradient.
• To integrate connectomics and transcriptomics to understand these effects and their association with cognitive function and gene expression.

Main Methods:

• Resting-state functional MRI data from 140 participants (86 CD patients, 54 controls) were analyzed.
• Alterations in the principal gradient were examined and correlated with cortisol levels, cognitive domains, and gene expression profiles.

Main Results:

• CD patients showed altered connectome patterns, converging along the principal gradient compared to controls.
• Gradient values in specific brain regions (prefrontal, sensorimotor cortices) correlated with cortisol levels.
• Altered regions involved sensory processing and higher cognition, linking to gene expression patterns in synaptic components.

Conclusions:

• Converged alterations in the principal functional gradient may link hypercortisolism to cognitive impairments in CD.
• These changes may involve genes regulating synaptic function, offering insights into CD's neurological impact.