Controllability modulates the anticipatory response in the human ventromedial prefrontal cortex

Abstract

Research has consistently shown that control is critical to psychological functioning, with perceived lack of control considered to play a crucial role in the manifestation of symptoms in psychiatric disorders. In a model of behavioral control based on non-human animal work, Maier et al. (2006) posited that the presence of control activates areas of the ventromedial prefrontal cortex (vmPFC), which in turn inhibit the normative stress response in the dorsal raphe nucleus and amygdala. To test Maier's model in humans, we investigated the effects of control over potent aversive stimuli by presenting video clips of snakes to 21 snake phobics who were otherwise healthy with no comorbid psychopathologies. Based on prior research documenting that disrupted neural processing during the anticipation of adverse events can be influenced by different forms of cognitive processing such as perceptions of control, analyses focused on the anticipatory activity preceding the videos. We found that phobics exhibited greater vmPFC activity during the anticipation of snake videos when they had control over whether the videos were presented as compared to when they had no control over the presentation of the videos. In addition, observed functional connectivity between the vmPFC and the amygdala is consistent with previous work documenting vmPFC inhibition of the amygdala. Our results provide evidence to support the extension of Maier's model of behavioral control to include anticipatory function in humans.

Keywords: PPI; amygdala; anticipation; controllability; fMRI; phobia; vmPFC.

Figure 1

Example trials. Left: a controllable snake trial where participant did not press the button fast enough and saw a video of a snake (left branch) or where participant pressed the button fast enough and did not see a video of a snake (right branch). Right: an uncontrollable snake trial where participant saw a video of a snake (left branch) or where participant did not see a video of a snake (right branch). The cue, presented for 3 s, was either yellow indicating an uncontrollable trial or blue indicating a control trial. The letter S indicated the potential video contained a snake. Following the cue, a fixation cross appeared for 1–7 s. We modeled the anticipation period as the time of the cue plus fixation cross. Following the fixation cross, a red square would appear, and the participant pressed a button as quickly as possible. Depending on the trial type and speed of the response, either a video or fixation cross would appear for 3 s. This was followed by another fixation cross for 1–7 s. If the participant saw a video, then they had 5 s to answer a rating question using a Likert scale. The scale was followed by a final fixation cross for 1–5 s before the onset of the next trial.

Figure 2

Anticipatory ventromedial prefrontal cortex (vmPFC) response showing the effect of controllability. Top: cortical surface renderings of the controllable snake (cS) minus uncontrollable snake (uS) contrast using multi-fiducial mapping in CARET with the strongest voxel within 2.5 mm of the surface (Van Essen, 2005). Results were thresholded at p < 0.05 cluster corrected. Brighter colors represent stronger effect or more overlap between the surfaces in the multi-fiducial map and can be interpreted as the most likely area of a strong effect. Bottom: the BOLD response in the cluster for cS, uS, and their difference. Error bars are SEM.

Figure 3

Anticipatory activations showing the effect of stimulus. Cortical surface renderings of snake (S) minus fish (F) contrast using multi-fiducial mapping in CARET with the strongest voxel within 2.5 mm of the surface (Van Essen, 2005). Results were thresholded at p < 0.05 cluster corrected. Bottom: heightened anticipatory activity reflected in greater activation in the ventromedial prefrontal cortex (vmPFC) (A), bilateral anterior insula (B,C), pregenual anterior cingulate cortex (ACC) (D), regions spanning from the ACC to the anterior mid-cingulate cortex (aMCC) (E), and bilateral aMCC (F) preceding snake videos compared to fish videos (S > F).

Figure 4

Functional connectivity using generalized psychophysiological interactions (gPPI). Top: significantly greater connectivity during controllable snake (cS) compared to uncontrollable snake (uS) shown in a coronal slice through the amygdala and thalamus. Results were thresholded at p < 0.05 cluster corrected. Bottom: plots for the left and right amygdala clusters showing the PPI values. Error bars are SEM. a.u. = arbitrary units.