How cognitive performance‐induced stress can influence right VLPFC activation: An fMRI study in healthy subjects and in patients with social phobia

Abstract

The neural bases of interactions between anxiety and cognitive control are not fully understood. We conducted an fMRI study in healthy participants and in patients with an anxiety disorder (social phobia) to determine the impact of stress on the brain network involved in cognitive control. Participants performed two working memory tasks that differed in their level of performance-induced stress. In both groups, the cognitive tasks activated a frontoparietal network, involved in working memory tasks. A supplementary activation was observed in the right ventrolateral prefrontal cortex (VLPFC) in patients during the more stressful cognitive task. Region of interest analyses showed that activation in the right VLPFC decreased in the more stressful condition as compared to the less stressful one in healthy subjects and remain at a similar level in the two cognitive tasks in patients. This pattern was specific to the right when compared to the left VLPFC activation. Anxiety was positively correlated with right VLPFC activation across groups. Finally, left dorsolateral prefrontal cortex (DLPFC) activation was higher in healthy subjects than in patients in the more stressful task. These findings demonstrate that in healthy subjects, stress induces an increased activation in left DLPFC, a critical region for cognitive control, and a decreased activation in the right VLPFC, an area associated with anxiety. In patients, the differential modulation between these dorsal and ventral PFC regions disappears. This absence of modulation may limit anxious patients' ability to adapt to demanding cognitive control tasks.

Functional network dysfunction in anxiety and anxiety disorders

“…Increased activity in the VLPFC to the onset of non-emotional stimuli has been reported in patients with social phobia 50 and in adolescents with high trait anxiety. 43 In the study of social phobia, the magnitude of VLPFC activity correlated positively with measures of anxiety during a difficult task.…”

“…43 In the study of social phobia, the magnitude of VLPFC activity correlated positively with measures of anxiety during a difficult task. 50 The P200 response is a positive event-related potential (ERP) that appears 200 ms following stimulus onset and may be a marker of attention shifts including stimulus-driven shifts; the magnitude of this measure is increased in individuals with high trait anxiety 51, 52 or high anxious arousal 53 when they view non-emotional stimuli or a combination of emotional and non-emotional stimuli. Individuals with high anxiety may show a similar increase in activity in the ventral attention network for emotionally-laden stimuli as they do for neutral stimuli 33, 52, 54, 55 although this activity has been hypothesized to represent a compensatory response as it was shown to be negatively correlated with measures of anxiety in individuals with generalized anxiety disorder.…”

Neural responses to social threat and predictors of cognitive behavioral therapy and acceptance and commitment therapy in social anxiety disorder

“…We expected to see relatively greater activations in SAD individuals compared to healthy controls, particularly in amygdala, insula, and ACC, reflecting increased sensitivity to rejection and potential social threat, and that neural responses to rejection stimuli would be moderated by SAD severity, given evidence that severity of maladaptive processing of social information in SAD covaries with disorder severity (e.g., Ball et al, 2012; Brühl et al, 2011; Evans et al, 2008; Frick et al, 2013b; Goldin et al, 2009; Koric et al, 2012; Shah et al, 2009). Finally, we predicted that increased pre-treatment amygdala, ACC, prefrontal, occipital, and temporal activity would predict subsequent CBT/ACT outcomes consistent with previous related work demonstrating such a relationship (Klumpp et al, 2014; McClure et al, 2007; Siegle et al, 2006).…”

“…Despite the elegant simplicity of static facial expressions, there has been a growing emphasis on other types of stimuli with putatively greater ecological validity such as imagining feared social situations (Blair et al, 2010; Boehme et al, 2014; Nakao et al, 2011), anticipation of public speaking (Boehme et al, 2013; Cremers et al, 2015), performance evaluation (Gimenez et al, 2012; Koric et al, 2012; Pujol et al, 2013), and exposure to social criticism (Blair et al, 2008a; Goldin et al, 2009, 2011b; Ziv et al, 2013a). Such paradigms can provide valuable insights into the more complex processes that are typically encountered in SAD.…”

Have we met before? Neural correlates of emotional learning in women with social phobia

“…22,23 Altered activation patterns in prefrontal executive brain areas (i.e., prefrontal cortex [PFC]) have also been reported in patients with social phobia. [24][25][26] Theories suggest that prefrontal activation may downregulate anxiety-sensitive subcortical brain areas. [27][28][29] This interplay may be disturbed in patients with pathological anxiety, possibly resulting in increased amygdala responsiveness.…”