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. 2010 Sep 22;36(1):183–206. doi: 10.1038/npp.2010.166

Figure 3.

Figure 3

(a) Schematic representation of frontocingulate and frontolimbic interactions associated with adaptive forms of reflective, self-focused processing, as well as adaptive regulation of cognition and emotions. In controls, increased resting rACC activity as well as functional coupling (positive correlations) between the rACC and amygdala (see arrow 1) are observed during resting states (Margulies et al, 2007) and self-referential processing (Schmitz and Johnson, 2006). When confronted with cognitive or affective challenges, healthy controls show increased coupling (positive correlations) between the (1) rACC and DLPFC (arrow 2; Holmes and Pizzagalli, 2008b; Etkin et al, 2006) and (2) DLPFC and dACC (arrow 3; Aizenstein et al, 2009; Fox et al, 2005; Margulies et al, 2007; Schmitz and Johnson, 2006). The interplay among these regions is hypothesized to reduce task-induced rACC activation (arrow 4; Drevets and Raichle, 1998; Fox et al, 2005; Margulies et al, 2007) and downregulate amygdala activation, fostering adaptive regulation of cognition and emotions. (b) Relative to controls, MDD subjects show stronger functional coupling (positive correlations) between the rACC and the amygdala during negative self-referential processing (arrow 1; Yoshimura et al, 2010) as well as reduced structural connectivity between these two regions (arrow 5; Cullen et al, 2010). In addition, relative to controls, MDD subjects show reduced functional connectivity between the (1) rACC and DLPFC (arrow 2; Holmes and Pizzagalli, 2008b; Siegle et al, 2007) and (2) DLPFC and dACC (arrow 3; Aizenstein et al, 2009; Schlösser et al, 2008), but abnormally elevated functional connectivity between the dACC and rACC (arrow 4; Schlösser et al, 2008) during cognitive and/or affective challenges. The dysregulated interplay among these regions is hypothesized to lead to failures to deactivate the rACC and amygdala during affective and cognitive challenges, fostering the emergence of maladaptive forms of rumination, and ultimately treatment nonresponse. Numbers do not reflect chronological unfolding of interactions among brain regions.