Generalized social anxiety disorder (gSAD) is characterized by extreme fears of potential scrutiny encompassing most social situations [1
] and, therefore, can lead to impaired functioning in educational, occupational, and interpersonal domains [1
]. Clinical manifestations of gSAD reflect a heightened threat processing system. These include excessive attention to negative social-signals (e.g., angry, fearful facial expressions [5
]); fear-based physiological responses (autonomic changes) in anticipation of [6
], or during [8
], anxiety-evoking situations; and negative predictions about social events [9
Thus far, models of the neural pathophysiology of gSAD have focused on an enhanced threat processing system that have fundamentally evolved from amygdala-centric ‘functional’ brain activation paradigms. In light of the central role amygdala plays in mediating fear and threat-related processing [7
], its response to emotional information has been a predominant focus in affective neuroscience. As one example, when coupled with functional neuroimaging, perceptual matching tasks are designed to isolate the influence of emotional face content by contrasting a matching face condition with a sensorimotor control condition (i.e., matching shapes) and to robustly elicit amygdala response in healthy volunteers [13
]. Building on this paradigm, studies of gSAD have shown amygdala reactivity to threat exceeds that of healthy individuals [17
] and the extent of this reactivity has been shown to reflect symptom severity [19
There is increasing evidence that the neural substrates of gSAD extend beyond the amygdala. In addition, there is a growing realization that functional neuroimaging paradigms should move beyond perceptual assessment tasks that primarily probe subcortical reactivity in key emotion processing regions. First, accumulating data point to insula hyper-reactivity in regard to processing negative emotional information in gSAD [20
], and evidence of a correlation between anterior insula (aINS) reactivity to threat-relevant cues and symptom severity [24
] also supports the notion that exaggerated aINS reactivity underlies anxiety disorders [28
]. It has been posited that negative beliefs are mediated by feeling states, a core function of the aINS [30
]. That is, aberrant insula activiation in anxiety is thought to be driven by sensitivity to aversive interoceptive signals and/or inaccurate interpretations of ordinary changes in bodily state [28
]. Second, the prefrontal cortex (PFC) has reciprocal connections with the amygdala [32
] and aINS [30
], yet less is known about prefrontal mechanisms in gSAD. The relative gap in knowledge may relate to the interest in aberrant amygdala activation in anxiety and use of perceptual matching tasks, which are not well-validated to probe PFC regions.
Several functional neuroimaging tasks exist that are known to robustly recruit PFC areas by engaging cognitive functions such as ‘top down’ attentional control—that is, the ability to effectively resolve the type of conflict that occurs when cognitive goals compete with salient distractors for limited processing resources [40
]. For example, to reflect the competition for processing resources imposed by distractors, tasks such as the emotional counting Stroop [48
], modified dot probe detection [51
], and “faces/houses” [40
] have in common the rapid and simultaneous presentation of non-emotional, task-relevant stimuli and salient distractors (e.g., 500 ms or less; [40
]). Studies using such tasks have shown that anxiety-prone [40
] and clinically anxious patients [49
], including those with gSAD [49
], exhibit deficiencies in the recruitment of the anterior cingulate cortex (ACC) and other emotion regulation areas (e.g., dorsolateral PFC) in the presence of threat distractors. Excessive attention to threat appears to encompass impoverished top-down control at least when the window of information processing is markedly restricted (i.e., when visual processing is fast).
Current models propose that there is a balance between attending to the task at hand and to the emotional salience that surround the given task. Resolving emotional conflict must occur in the context that salient emotional cues not only capture but sustain visual attention [58
]. Consequently, prefrontal areas should engage during the maintenance of goal-directed attention even when the window of information processing is extended to that of direct emotion processing.
In order to capture this balance, we adapted the face matching task into a relatively slow, easy-to-perform blocked perceptual matching task known as the “Emotional Faces Shifting Attention Task” (EFSAT), which requires subjects to shift their attention towards and away from emotional faces. In contrast to the traditional faces-only and shapes-only images, in EFSAT both image types were configured to be in the same field of view (Figure ). Therefore, the instruction to “Match Shapes” directed attention away
from emotional faces whereas “Match Faces” directed attention towards
emotional faces. Analogous to traditional perceptual assessment tasks, each matching trial was presented for 4 sec in back-to-back blocks. In a recent study [59
], we demonstrated the modification was successful as healthy volunteers engaged the amygdala to “Match Faces” and the rostral ACC to “Match Shapes” indicating the ACC effectively impeded the processing of task-irrelevant emotional faces presented alongside shapes. Thus, EFSAT complements traditional attentional control paradigms shown to recruit PFC areas.
Schematic of an exemplar Match Faces and Match Shapes blocks in the Emotional Faces Shifting Attention Task (EFSAT).
In an effort to assess neural correlates of sustained attentional control in gSAD, participants performed the EFSAT during functional MRI. Our predictions for emotion processing (Match Faces
Match Shapes) were individuals with gSAD compared to demographically matched healthy controls (HC) would demonstrate: 1) exaggerated amygdala and anterior insula reactivity, 2) a positive relationship between activation in these regions and symptom severity, and 3) subcortical effects would be most pronounced when the faces constituted social signals of threat (angry and fear). Regarding attentional control (Match Shapes
Match Faces), we predicted gSAD compared to HC would exhibit: 1) reduced ACC activation, and 2) deficient ACC response would be most pronounced in the presence of distracting threat faces. Lastly, given reciprocal subcortical-ACC associations, we hypothesized insula activation to emotion processing would negatively correlate with ACC response during attentional control across participants.