Resting-State Functional Connectivity in Patients with Long-Term Remission of Cushing's Disease

Abstract

Glucocorticoid disturbance can be a cause of psychiatric symptoms. Cushing's disease represents a unique model for examining the effects of prolonged exposure to high levels of endogenous cortisol on the human brain as well as for examining the relation between these effects and psychiatric symptomatology. This study aimed to investigate resting-state functional connectivity (RSFC) of the limbic network, the default mode network (DMN), and the executive control network in patients with long-term remission of Cushing's disease. RSFC of these three networks of interest was compared between patients in remission of Cushing's disease (n=24; 4 male, mean age=44.96 years) and matched healthy controls (n=24; 4 male, mean age=46.5 years), using probabilistic independent component analysis to extract the networks and a dual regression method to compare both groups. Psychological and cognitive functioning was assessed with validated questionnaires and interviews. In comparison with controls, patients with remission of Cushing's disease showed an increased RSFC between the limbic network and the subgenual subregion of the anterior cingulate cortex (ACC) as well as an increased RSFC of the DMN in the left lateral occipital cortex. However, these findings were not associated with psychiatric symptoms in the patient group. Our data indicate that previous exposure to hypercortisolism is related to persisting changes in brain function.

Figure 1

Resting-state networks of interest. (a) The limbic network. (b) The default mode network. (c) The executive control network. Images are z-statistics, overlaid on the MNI-152 1 mm standard brain. The left hemisphere of the brain corresponds to the right side of the coronal and transversal images.

Figure 2

Resting-state functional connectivity of the limbic network. (a) Depicted here are the within-group mean z-scores and the between-group effect for the limbic network. Images representing the statistics are overlaid on the MNI-152 1 mm standard brain. The between-group effect is displayed as p-statistics, TFCE corrected for family-wise error (p<0.05). The between-group effect shows increased RSFC between the limbic network and the subgenual ACC. (b) Distribution of the mean individual z-scores within the subgenual ACC. Depicted in red are the patients with long-term remission of Cushing's disease, depicted in blue are the matched healthy controls, and both are sorted from smallest to highest z-score. A full colour version of this figure is available at the Neuropsychopharmacology journal online.

Figure 3

Resting-state functional connectivity of the default mode network. (a) Depicted here are the within-group mean z-scores and between-group effect for the default mode network. Images representing the statistics are overlaid on the MNI-152 1 mm standard brain. The between-group effect is displayed as p-statistics, TFCE corrected for family-wise error (p<0.05). The between-group effect shows increased RSFC between the default mode network and a small cluster located in the superior division of the left lateral occipital cortex. (b) Distribution of the mean individual z-scores within the superior division of the left lateral occipital cortex. Depicted in red are the patients with long-term remission of Cushing's disease, depicted in blue are the matched healthy controls, and both are sorted from smallest to highest z-score.