The neural basis of the abnormal self‐referential processing and its impact on cognitive control in depressed patients

Abstract

Persistent pondering over negative self-related thoughts is a central feature of depressive psychopathology. In this study, we sought to investigate the neural correlates of abnormal negative self-referential processing (SRP) in patients with Major Depressive Disorder and its impact on subsequent cognitive control-related neuronal activation. We hypothesized aberrant activation dynamics during the period of negative and neutral SRP in the rostral anterior cingulate cortex (rACC) and in the amygdala in patients with major depressive disorder. Additionally, we assumed abnormal activation in the fronto-cingulate network during Stroop task execution. 19 depressed patients and 20 healthy controls participated in the study. Using an event-related functional magnetic resonance imaging (fMRI) design, negative, positive and neutral self-referential statements were displayed for 6.5 s and followed by incongruent or congruent Stroop conditions. The data were analyzed with SPM8. In contrast to controls, patients exhibited no significant valence-dependent rACC activation differences during SRP. A novel finding was the significant activation of the amygdala and the reward-processing network during presentation of neutral self-referential stimuli relative to baseline and to affective stimuli in patients. The fMRI analysis of the Stroop task revealed a reduced BOLD activation in the right fronto-parietal network of patients in the incongruent condition after negative SRP only. Thus, the inflexible activation in the rACC may correspond to the inability of depressed patients to shift their attention away from negative self-related stimuli. The accompanying negative affect and task-irrelevant emotional processing may compete for neuronal resources with cognitive control processes and lead thereby to deficient cognitive performance associated with decreased fronto-parietal activation.

Cortical morphometric predictors of autonomic dysfunction in generalized anxiety disorder

“…The rostral ACC is more active when participants are asked to regulate conflicting emotional information (Etkin et al, 2006), avoid attending to irrelevant emotional information (Bishop et al, 2004), or exercise top-down control upon processing of emotional stimuli (Ochsner et al, 2004), highlighting its joint roles in emotion representation and regulation (Smith et al, 2014, Smith and. In line with this view, inflexible activation in the rostral ACC has been associated with the inability to shift attention away from negative self-related stimuli (Wagner et al, 2015). Interestingly, in a previous fMRI study reduced activation of the ACC was reported during feelings of guilt in patients with obsessivecompulsive disorder, who, similarly to the present sample with GAD, had significantly higher STAI trait scores than controls (Basile et al, 2014).…”

Noninvasive brain stimulation treatments for addiction and major depression

“…MDD patients display a similar disruption of incentive salience for primary rewards and instead become attuned to disease‐specific stimuli. For example, the rostral ACC and ventral striatum are hypoactive during reward feedback and hyperactive during self‐referential negative processing . MDD patients also show an absence of ventral striatal and VMPFC/OFC inactivation for pleasant sights and tastes but heightened activation in the caudate in response to viewing aversive images .…”

“…For example, the rostral ACC and ventral striatum are hypoactive during reward feedback [110][111][112] and hyperactive during self-referential negative processing. 113,114 MDD patients also show an absence of ventral striatal and VMPFC/OFC inactivation for pleasant sights and tastes but heightened activation in the caudate in response to viewing aversive images. 115 Altered responses from the subgenual cingulate and OFC are also found in MDD during rumination and negative self-focus.…”

Brain networks for engaging oneself in positive-social emotion regulation

“…Previous studies have identified the temporoparietal junction (TPJ), dmPFC and precuneus as the core neural system involved in mentalizing (Spreng et al, 2009), mental-state attribution (Teufel et al, 2010), self-referential processing and assessment of the emotional states in social situations (Buckner and Carroll, 2007;Reeck et al, 2016;Zaki and Ochsner, 2012). Impairments of the self-referential neural system is often associated with depression (Lemogne et al, 2009;Wagner et al, 2015), schizophrenia (Harvey et al, 2013) and autism (Murdaugh et al, 2014;Oberman and Ramachandran, 2007;Zaki and Ochsner, 2012) disorders.…”