Prefrontal thinning affects functional connectivity and regional homogeneity of the anterior cingulate cortex in depression

Abstract

Major depressive disorder (MDD) is associated with structural and functional alterations in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Enhanced ACC activity at rest (measured using various imaging methodologies) is found in treatment-responsive patients and is hypothesized to bolster treatment response by fostering adaptive rumination. However, whether structural changes influence functional coupling between fronto-cingulate regions and ACC regional homogeneity (ReHo) and whether these functional changes are related to levels of adaptive rumination and treatment response is still unclear. Cortical thickness and ReHo maps were calculated in 21 unmedicated depressed patients and 35 healthy controls. Regions with reduced cortical thickness defined the seeds for the subsequent functional connectivity (FC) analyses. Patients completed the Response Style Questionnaire, which provided a measure of adaptive rumination associated with better response to psychotherapy. Compared with controls, depressed patients showed thinning of the right anterior PFC, increased prefrontal connectivity with the supragenual ACC (suACC), and higher ReHo in the suACC. The suACC clusters of increased ReHo and FC spatially overlapped. In depressed patients, suACC ReHo scores positively correlated with PFC thickness and with FC strength. Moreover, stronger fronto-cingulate connectivity was related to higher levels of adaptive rumination. Greater suACC ReHo and connectivity with the right anterior PFC seem to foster adaptive forms of self-referential processing associated with better response to psychotherapy, whereas prefrontal thinning impairs the ability of depressed patients to engage the suACC during a major depressive episode. Bolstering the function of the suACC may represent a potential target for treatment.

Figures

Figure 1

Brain regions showing structural and functional connectivity (FC) differences in patients with major depressive disorder (MDD) and healthy controls. (a) Cortical thinning in patients with MDD compared with healthy controls was identified in the right rostral middle frontal cortex. The cluster is rendered in blue on the inflated surface after correction for multiple comparisons. (b) Depressed patients exhibited increased functional connectivity of the right rostral middle frontal cortex with the supragenual anterior cingulate cortex (suACC) compared with healthy controls. (c) Scatterplot shows the correlation between FC strength of the right rostral middle frontal cortex with the suACC (z-scores) and the standardized residual scores of self-focus rumination in depressed patients (solid line; r2=0.36).

Figure 2

Brain region showing regional homogeneity differences in patients with major depressive disorder (MDD) and healthy controls. (a) Supragenual anterior cingulate cortex cluster of increased regional homogeneity (ReHo) in depressed patients compared with healthy controls (HC). (b) Scatterplots show the correlation between ReHo z-scores and functional connectivity (FC) strength. The correlation was significant in patients with MDD (solid line; r2=0.39) and in healthy controls (HC: dashed line; r2=0.12). (c) Scatterplots show the correlation between ReHo z-scores and cortical thickness. The correlation was significant in patients with MDD (solid line; r_kendall's tau=0.45) but not in HC (dashed line; r_kendall's tau=0.15).