Clarifying the Role of the Rostral dmPFC/dACC in Fear/Anxiety: Learning, Appraisal or Expression?

<div><p>Recent studies have begun to carve out a specific role for the rostral part of the dorsal medial prefrontal cortex (dmPFC) and adjacent dorsal anterior cingulate cortex (dACC) in fear/anxiety. Within a novel general framework of dorsal mPFC/ACC areas subserving the appraisal of threat and concomitant expression of fear responses and ventral mPFC/ACC areas subserving fear regulation, the rostral dmPFC/dACC has been proposed to specifically mediate the conscious, negative appraisal of threat situations including, as an extreme variant, catastrophizing. An alternative explanation that has not been conclusively ruled out yet is that the area is involved in fear learning. We tested two different fear expression paradigms in separate fMRI studies (study 1: instructed fear, study 2: testing of Pavlovian conditioned fear) with independent groups of healthy adult subjects. In both paradigms the absence of reinforcement precluded conditioning. We demonstrate significant BOLD activation of an identical rostral dmPFC/dACC area. In the Pavlovian paradigm (study 2), the area only activated robustly once prior conditioning had finished. Thus, our data argue against a role of the area in fear learning. We further replicate a repeated observation of a dissociation between peripheral-physiological fear responding and rostral dmPFC/dACC activation, strongly suggesting the area does not directly generate fear responses but rather contributes to appraisal processes. Although we succeeded in preventing extinction of conditioned responding in either paradigm, the data do not allow us to definitively exclude an involvement of the area in fear extinction learning. We discuss the broader implications of this finding for our understanding of mPFC/ACC function in fear and in negative emotion more generally.</p> </div

Areas activated during Instructed and Uninstructed Fear.

<p>Areas activated in the contrasts CS+>CS− and CS−>CS+ at p_uncorr<0.001, k = 10, in Instructed Fear (study 1, IF-Test) and Uninstructed Fear (study 2, UF-Test).</p

Instructed fear (study 1): Skin conductance.

<p>SCRs show stable threat responding across the two test runs (IF-Test1, IF-Test2). Error bars: s.e.m.</p

Uninstructed fear (study 2): Behavior.

<p>SCRs (<b>A</b>), CS valence (<b>B</b>), and UCS expectancy (<b>C</b>) during the two conditioning runs (UF-Cond1, UF-Cond2) and the test run (UF-Test). SCR analysis (<b>A</b>) was restricted to unpaired CS+s and CS−s, and responses were averaged across each run. Rating data (<b>B, C</b>) are normalized to the baseline rating given after habituation and before conditioning. Responses to the refresher CS at the outset of the UF-Test run (see <b>Methods</b>) are not shown. VAS, visual analog scale. Error bars: s.e.m.</p

Uninstructed fear (study 2): Rostral dmPFC/dACC activation.

<p>(<b>A</b>) Contrast ‘unpaired CS+>CS−’ at testing (UF-Test run). Display threshold: p<0.001 uncorrected. Activations superimposed on a canonical structural image. (<b>B</b>) Parameter estimates from the peak voxel during all three runs (UF-Cond1, UF-Cond2, UF-Test). Error bars: s.e.m.</p