Elsevier

NeuroImage

Volume 29, Issue 1, 1 January 2006, Pages 106-116
NeuroImage

Functional neuroanatomy of aversion and its anticipation

https://doi.org/10.1016/j.neuroimage.2005.06.068Get rights and content

Abstract

The capacity to anticipate aversive circumstances is central not only to successful adaptation but also to understanding the abnormalities that contribute to excessive worry and anxiety disorders. Forecasting and reacting to aversive events mobilize a host of affective and cognitive capacities and corresponding brain processes. Rapid event-related functional magnetic resonance imaging (fMRI) in 21 healthy volunteers assessed the overlap and divergence in the neural instantiation of anticipating and being exposed to aversive pictures. Brain areas jointly activated by the anticipation of and exposure to aversive pictures included the dorsal amygdala, anterior insula, dorsal anterior cingulate cortex (ACC), right dorsolateral prefrontal cortex (DLPFC), and right posterior orbitofrontal cortex (OFC). Anticipatory processes were uniquely associated with activations in rostral ACC, a more superior sector of the right DLPFC, and more medial sectors of the bilateral OFC. Activation of the right DLPFC in anticipation of aversion was associated with self-reports of increased negative affect, whereas OFC activation was associated with increases in both positive and negative affect. These results show that anticipation of aversion recruits key brain regions that respond to aversion, thereby potentially enhancing adaptive responses to aversive events.

Introduction

Signals preceding aversive events often serve to forecast impending danger, doom, or otherwise undesired outcomes. Anticipating negative events is a key component of worry and can be adaptive, leading to behavioral, emotional, and physiological adjustments in preparation for or prevention of aversive outcomes. The anticipation of aversion entails multiple affective and cognitive constituents, including threat detection, elicitation of unpleasant affect and anxiety, regulation of unpleasant emotions, attention to the expected source of the aversion, memory of relevant prior aversive events, and autonomic activity and initiation of motor programs to prime the organism for action and behavioral withdrawal. Unfortunately, anticipation and worry can become excessive and dysfunctional, a feature of various forms of psychopathology (e.g., panic disorder, generalized anxiety disorder, social anxiety disorder), and may evoke these anticipatory and response mechanisms unnecessarily.

Building on knowledge accrued from prior research identifying the functional neuroanatomy of processing aversive stimuli (Penfield and Faulk, 1955, Tomarken et al., 1990, Wheeler et al., 1993, Phillips et al., 1997, Phillips et al., 1998, Phillips et al., 2003, Phillips et al., 2004, Davidson and Irwin, 1999, Simpson et al., 2000, Calder et al., 2001, Davis and Whalen, 2001, Ostrowsky et al., 2002, LeDoux, 2002, Bentley et al., 2003, Murphy et al., 2003, Wicker et al., 2003), research efforts can now turn to novel experimental designs that allow for the dissection of the various constituent components, such as anticipatory and reactivity processes (Chua et al., 1999, Ploghaus et al., 1999, Ueda et al., 2003, Wager et al., 2004). Research on anticipating pain, shock, and pharmacologically induced panic has implicated the insula and ACC (Chua et al., 1999, Javanmard et al., 1999, Ploghaus et al., 1999, Ploghaus et al., 2003, Sawamoto et al., 2000, Craig, 2003, Wager et al., 2004, Lorenz et al., 2005). Also relevant is the extensive literature on fear conditioning (Davis, 1992, LeDoux, 2002), including neuroimaging studies that have reported amygdala activation to a paired conditioned stimulus (CS+) on trials when the unconditioned stimulus was not presented (BĆ¼chel et al., 1998, LaBar et al., 1998).

This rapid event-related fMRI study utilized warning cues that predicted aversive pictures to assess activation in five brain regions serving functions relevant to the anticipation of and exposure to aversion, including the amygdala in the detection of motivationally salient events (Davidson and Irwin, 1999, Davis and Whalen, 2001), insula and ACC in the integration of sensory, affective, cognitive, autonomic, and motor processes (Augustine, 1996, Price, 2000, Critchley et al., 2000, Critchley et al., 2002b, Critchley et al., 2004, Critchley et al., 2005, Craig, 2002, Craig, 2003, Singer et al., 2004), right DLPFC in withdrawal-related unpleasant affect (Davidson and Irwin, 1999, Davidson, 2002, Nitschke and Heller, 2002), and OFC in decoding the affective value of a stimulus or event (Rolls, 1999, Rolls, 2004, Nitschke et al., 2004). Accordingly, we predicted that these five hypothesized areas would activate both in anticipation of and response to the aversive pictures. In addition, we tested whether subregions of these areas would show preferential activation for anticipatory processing, as has been reported for the insula, ACC, DLPFC, and OFC (e.g., Murtha et al., 1996, Ploghaus et al., 1999, Ploghaus et al., 2003, O'Doherty et al., 2002, Wager et al., 2004). Finally, we hypothesized that right DLFPC activation would be associated with a self-report measure of withdrawal-related unpleasant affect (Davidson, 2002, Nitschke and Heller, 2002) and that OFC activation would be associated with pleasant and unpleasant affect (Rolls, 1999, Nitschke et al., 2004).

Section snippets

Subjects

Subjects were 21 right-handed undergraduate students (11 women and 10 men, mean age 19) who responded to flyers posted in the Department of Psychology at the University of Wisconsin-Madison. They were free of any medical or neurological problems, took no medications, and had no current psychiatric diagnoses as determined by the Structured Clinical Interview for the DSM-IV (SCID; First et al., 1996). All subjects gave informed consent in accord with study approval by the Human Subjects Committee

Experimental paradigm and stimuli

As shown in Fig. 1, each trial began with a 0.5-s warning cue (minus sign for aversive pictures, circle for neutral pictures) followed by a 2.5-s or 4.5-s black screen (pseudo-randomized within valence) and then two contiguous 0.5-s presentations of either aversive or neutral pictures. Another black screen for 16 or 18 s ended each 22-s trial. This trial structure was selected in an attempt to optimize methodological parameters for effectively distinguishing anticipation and picture reactivity

Results

A conjunction analysis of the effects for the anticipation and picture periods tested our primary hypothesis that anticipation of aversive pictures as well as exposure to them would activate the amygdala, insula, ACC, right DLPFC, and OFC. Confirmatory results were found for the bilateral dorsal amygdala, bilateral anterior insula, dorsal ACC, right DLPFC, and right posterior OFC (Fig. 2; Table 1). The less stringent conjunction analysis method implemented in SPM99 and SPM2 (Friston et al.,

Discussion

This study found that five key brain areas repeatedly implicated in previous research on aversion were activated not only when subjects viewed aversive visual stimuli but also in anticipation of them. The design of the rapid event-related fMRI paradigm, in tandem with advancing sophistication of data processing procedures, afforded the ability to delineate the respective contributions of the anticipation and picture periods to the hemodynamic responses elicited by aversion. Areas recruited both

Acknowledgments

We gratefully acknowledge Michael Anderle, Krystal Cleven, Kelli Ferber, Tom Johnstone, Hyejeen Lee, Terrence Oakes, Adrian Pederson, Alissa Possin, Thomas Ihde-Scholl, Brian Skinner, and Lesley Tarleton for their contributions to this project. JBN was supported by an NIMH Career Development Award (K08-MH63984), a Training Program in Emotion Research NIMH grant (T32-MH18931), and a Health Emotions Research Institute fellowship. RJD was supported by NIMH grants (MH40747, P50-MH52354, MH43454)

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