Abnormal hypothalamic functional connectivity associated with cognitive impairment in craniopharyngiomas

Area of Science:

• Neuroimaging
• Neurology
• Endocrinology

Background:

• Craniopharyngioma (CP) is a brain tumor that can affect the hypothalamus and surrounding structures.
• Neurocognitive deficits are common in CP patients, but the underlying functional mechanisms are not fully understood.

Purpose of the Study:

• To characterize resting-state functional connectivity (rsFC) in hypothalamic and extrahypothalamic nuclei of CP patients.
• To investigate the relationship between rsFC patterns and neurocognitive performance in CP patients.

Main Methods:

• Whole-brain seed-to-voxel analyses compared rsFC between 92 CP patients and 40 healthy controls.
• Regression analyses correlated neurocognitive performance with rsFC maps.
• Spectral Dynamic Causal Modeling (DCM) explored the hypothalamus circuit related to cognitive impairment.

Main Results:

• CP patients exhibited reduced rsFC in hypothalamic nuclei, particularly within the default mode network (DMN) regions (anterior and posterior cingulate cortices).
• Significant rsFC reductions were also observed in extrahypothalamic areas, including the limbic system (caudate nuclei, corpus callosum, fornix, thalamus).
• Worse cognitive performance correlated with abnormal hypothalamic rsFC within the DMN; DCM identified a hypothalamus-DMN circuit contributing to cognitive deficits.

Conclusions:

• Craniopharyngiomas impacting the hypothalamus disrupt hypothalamic and extrahypothalamic rsFC with DMN and limbic system areas.
• The severity of rsFC disruption correlates with the extent of hypothalamic involvement.
• Abnormal functional connectivity within the hypothalamus-DMN circuit represents a key mechanism underlying cognitive impairment in CP patients.