Failure to Regulate: Counterproductive Recruitment of Top-Down Prefrontal-Subcortical Circuitry in Major Depression

By Tom Johnstone, C. V. van Reekum, Heather L. Urry, Ned H. Kalin, Richard J. Davidson. Journal of Neuroscience, 2007

1,059 citations recorded by the source corpus.

Although depressed mood is a normal occurrence in response to adversity in all individuals, what distinguishes those who are vulnerable to major depressive disorder (MDD) is their inability to effectively regulate negative mood when it arises. Investigating the neural underpinnings of adaptive emotion regulation and the extent to which such processes are compromised in MDD may be helpful in understanding the pathophysiology of depression. We report results from a functional magnetic resonance imaging study demonstrating left-lateralized activation in the prefrontal cortex (PFC) when downregulating negative affect in nondepressed individuals, whereas depressed individuals showed bilateral PFC activation. Furthermore, during an effortful affective reappraisal task, nondepressed individuals showed an inverse relationship between activation in left ventrolateral PFC and the amygdala that is mediated by the ventromedial PFC (VMPFC). No such relationship was found for depressed individuals, who instead show a positive association between VMPFC and amygdala. Pupil dilation data suggest that those depressed patients who expend more effort to reappraise negative stimuli are characterized by accentuated activation in the amygdala, insula, and thalamus, whereas nondepressed individuals exhibit the opposite pattern. These findings indicate that a key feature underlying the pathophysiology of major depression is the counterproductive engagement of right prefrontal cortex and the lack of engagement of left lateral-ventromedial prefrontal circuitry important for the downregulation of amygdala responses to negative stimuli.

Subfields: Cognitive Neuroscience, Experimental and Cognitive Psychology

View Paper: https://www.semanticscholar.org/paper/53f717aeb19988816f7c869404ed4671f4fffa6b

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Citations in the corpus

Cognitive reappraisal of emotion: a meta-analysis of human neuroimaging studies. (2014, background): “Support for this comes from several studies have found that connectivity between vmPFC and subcortical structures differs between individuals as a function of psychiatric status (Johnstone et al. 2007; Erk et al. 2010), genetics (Schardt et al.”
The neurobiology of psychedelic drugs: implications for the treatment of mood disorders (2010, background): “show reduced PFC activity when executive control is engaged, and might suffer from decreased top-down inhibition of amygdala activit”
Emotion and the Prefrontal Cortex: An Integrative Review (2017, background): “It is widely recognized that the PFC plays a central role in emotion regulation (Beauregard, Levesque, & Bourgouin, 2001; Etkin et al., 2015; Johnstone et al., 2007; McRae et al., 2012; Ochsner et al., 2002; Ochsner & Gross, 2005; Ochsner & Gross, 2014; Quirk & Beer, 2006; Wager et al., 2008).”
Emotion Regulation in Depression: Relation to Cognitive Inhibition (2010, background): “Interestingly, Johnstone, van Reekum, Urry, Kalin, and Davidson ( 2007 ) recently reported that during reappraisal of emotional pictures, there was a correlation within non-depressed individuals (but not within depressed persons) between increased dorsolateral prefrontal cortex (DLPFC) activation an”
The evolution of the cognitive model of depression and its neurobiological correlates. (2008, background): “Johnstone and colleagues (59) point out that a key feature underlying the pathophysiology of major depression is the dysfunctional engagement of the right prefrontal cortex and the lack of engagement of the left lateral ventral medial prefrontal circuitry, important for the down-regulation of amygda”
Having a word with yourself: Neural correlates of self-criticism and self-reassurance (2010, background): “The VLPFC is associated with the top–down regulation of limbic regions, implicated in emotional processing (Eippert et al., 2007), and also in studies of emotional reappraisal of negatively valenced stimuli (Johnstone et al., 2007, Ochsner et al., 2004 ).”
Whole Brain Resting-State Analysis Reveals Decreased Functional Connectivity in Major Depression (2010, positive): “In depression, several studies have shown abnormal functional connectivity (FC) during both cognitive and emotional task paradigms (Urry et al., 2006; Johnstone et al., 2007; Chen et al., 2008; Matthews et al., 2008),”
Pupil diameter covaries with BOLD activity in human locus coeruleus (2014, result): “While several previous studies have combined pupillometry with fMRI [Critchley et al., 2005; Johnstone et al., 2007; Siegle et al., 2003; Sterpenich et al., 2006], a link between BOLD activity localized to the LC and concurrently recorded pupil diameter has not been reported previously.”