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.

Relationship between neurotoxic kynurenine metabolites and reductions in right medial prefrontal cortical thickness in major depressive disorder

“…The significant decrease in cortical thickness of BA24 and BA32 in MDD patients is partially consistent with the results of (Spati et al, 2015) who reported only one region of decreased cortical thickness in MDD - the right dorsal mid-anterior ACC. Similarly, reductions in thickness of the right rACC (Oertel-Knochel et al, 2015), the right dorsomedial PFC, including BA32 (Elvsashagen et al, 2013), and the left rACC (Foland-Ross et al, 2011; Lyoo et al, 2006) have been reported in patients with bipolar disorder.…”

Adolescent brain development and depression: A case for the importance of connectivity of the anterior cingulate cortex

“…Not surprisingly, given its importance to developmental psychopathology, connectivity of the ACC has been implicated in each of these research directions for depression (e.g. Barrett et al, 2004; Leaver et al, 2016; Spati et al, 2015). Research in this field could also, ultimately, identify new brain targets for intervention.…”

Ruminative brooding is associated with salience network coherence in early pubertal youth

“…Interestingly, this hyperconnectivity is also associated with increased rumination (Spati et al , 2015). Further, graph theoretic metrics indicate that the dACC is more strongly integrated with and more centrally positioned among other nodes of depressed individuals’ neural networks (Onoda and Yamaguchi, 2015), suggesting that, in depression, networks are functionally organized to readily send salient information to other networks for further consolidation and goal modulation.…”