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

Abstract

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.

Neural correlates of pupil dilation during human fear learning

“…Although our data cannot provide evidence for a causal influence of dACC on pupil responses, we propose that at least part of this association could be explained by threat appraisal, which has been related to dACC activity in previous work (Etkin, Egner, & Kalisch, 2011;Maier et al, 2012;Mechias, Etkin, & Kalisch, 2010). In line with this, we found that pupil dilations in response to CS+ appear most robustly seconds after stimulus onset, just before US administration.…”

From Pavlov to PTSD: The extinction of conditioned fear in rodents, humans, and anxiety disorders

“…Fear conditioning or the expression of conditioned fear in healthy humans has been associated with activity in medial prefrontal brain regions such as dACC and vmPFC (Alvarez et al, 2008; Buchel et al, 1999; Buchel et al, 1998; Klucken et al, 2009; LaBar et al, 1998; Lang et al, 2009; Maier et al, 2012; Marschner, Kalisch, Vervliet, Vansteenwegen, & Buchel, 2008; Milad, Quirk, et al, 2007; Milad, Wright, et al, 2007; Morris & Dolan, 2004; Phelps, Delgado, Nearing, & LeDoux, 2004). SCRs during conditioning are correlated with fMRI response in dACC and dACC thickness (Milad, Quirk, et al, 2007), and with the rate of resting metabolism in dACC (Linnman et al, 2013).…”

A review on human reinstatement studies: an overview and methodological challenges

“…As instructed and uninstructed conditioning might tap different processes, this may translate into different behavioral and neural correlates (Mechias et al 2010;Maier et al 2012).…”