Anterior cingulate cortex modulates preparatory activation during certain anticipation of negative picture

Abstract

We studied the neural activation associated with anticipations of emotional pictures using functional magnetic resonance imaging (fMRI) by directly comparing certain with uncertain anticipation conditions. While being scanned with fMRI, healthy participants (n = 18) were cued to anticipate and then perceive emotional stimuli having predictable (i.e., certain) emotional valences (i.e., positive and negative), given a preceding cue, as well as cued stimuli of uncertain valence (positive or negative). During anticipation of pictures with certain negative valence, activities of supracallosal anterior cingulate cortex, ventrolateral prefrontal cortex, insula, and amygdala were enhanced relative activity levels that for the uncertain emotional anticipation condition. This result suggests that these brain regions are involved in anticipation of negative images, and that their activity levels may be enhanced by the certainty of anticipation. Furthermore, the supracallosal anterior cingulate cortex showed functional connectivity with the insula, prefrontal cortex, and occipital cortex during the certain negative anticipation. These findings are consistent with an interpretation that top-down modulation, arising from anterior brain regions, is engaged in certain negative anticipation within the occipital cortex. It is thought that the limbic system involving the amygdala, ACC, and insula, engaged emotional processes, and that the input system involving the visual cortex entered an idling state.

Introduction

Anticipation of emotional events is a key component of anxiety. Such anticipation can be adaptive for adjustments in behavior as well as for coping with emotional and physiological states by virtue of allowing an individual to prepare for and/or prevent aversive outcomes. Anticipation itself may entail multiple affective and cognitive constituents; these include threat detection, elicitation of unpleasant affect, regulation of unpleasant emotions, attentional orienting to an expected source of some event, memory of relevant prior negative events, and autonomic activity as well as initiation of motor programs that prime the organism for action and behavioral withdrawal (Nitschke, Sarinopoulos, Mackiewicz, Schaefer, & Davidson, 2006).

Functional neuroimaging has been used to study the neuronal correlates of various aspects in emotion processing (Phan, Wager, Taylor, & Liberzon, 2002). However, only recently have investigations been directed at identifying brain regions associated with the anticipation of pictorial emotional stimuli (Bermpohl et al., 2006; Herwig, Kaffenberger, Baumgartner, & Jancke, 2007; Nitschke et al., 2006; Simmons, Matthews, Stein, & Paulus, 2004; Simmons, Strigo, Matthews, Paulus, & Stein, 2006; Ueda et al., 2003). Most of the latter studies have employed emotional expectancy cues that can be characterized as instantiating high levels of certainty (i.e., cue validity) with regard to the emotional valence of a forthcoming picture; that is, these cues clearly and reliably predicted whether a negative or other type of picture would follow. Using this methodology, the expectation of a negative event, i.e., a negative expectancy, induced activation in dorsolateral prefrontal cortex (DLPFC; Nitschke et al., 2006), ventrolateral prefrontal cortex (VLPFC: Herwig, Baumgartner, et al., 2007; Herwig, Kaffenberger, et al., 2007; Simmons et al., 2004, Ueda et al., 2003), medial prefrontal cortex (MPFC; Ueda et al., 2003), orbitofrontal cortex (OFC; Nitschke et al., 2006), anterior cingulated cortex (ACC; Bermpohl et al., 2006; Herwig, Baumgartner, et al., 2007; Herwig, Kaffenberger, et al., 2007; Nitschke et al., 2006, Ueda et al., 2003), amygdala (Nitschke et al., 2006, Ueda et al., 2003), and insula (Nitschke et al., 2006, Simmons et al., 2004, Simmons et al., 2006).

In the present research, we are interested in whether the level of brain activation differs as function of the certainty (certain versus uncertain) of a given emotional anticipation. This idea is suggested by anticipation studies in other domains. For instance, anticipation of certain pain has been shown to involve the perigenual anterior cingulate cortex (PAC) (Ploghaus et al., 1999), whereas anticipation of uncertain pain is associated with activation in the supracallosal anterior cingulate cortex (SAC) (Porro, Cettolo, Francescato, & Baraldi, 2003). Similarly, in the reward domain, the anticipation of monetary reward produced larger activation in the SAC when higher outcome uncertainty was present (Critchley, Mathias, & Dolan, 2001). Bermpohl et al. (2006) has suggested that these findings extend to the domain of processing pictures that convey emotional meaning. In fact, the certainty of a given emotional expectancy has previously been shown to produce activation in parts of the emotional perception network including the PAC (Ueda et al., 2003); and Bermpohl et al. (2006) has also demonstrated that uncertain emotional expectancy involves the SAC. However, direct within-study comparisons of activations associated with certain versus uncertain emotional anticipations have not yet been undertaken. Therefore, we must acknowledge that distinctions between certain and uncertain emotional anticipation remain speculative.

In neuroimaging studies that involve anticipatory responses to emotional pictures, the control stimuli employed have typically consisted of neutral pictorial images that have low arousal levels (Bermpohl et al., 2006, Nitschke et al., 2006). It is important to note that activations of brain regions by emotional images, when compared with those activated by such neutral images preclude a straightforward explanation in terms of the affective valence of the emotional images. This is because arousal level may function as a confounding variable in such designs. That is, according to the international affective picture system (IAPS) (Lang, Bradley, & Cuthbert, 1999), emotional pictures (whether positive or negative) can be considered as highly arousing stimuli whereas valence-neutral pictures are typically found to be low arousing stimuli. Furthermore, recent studies have shown that emotional intensity and valence differ not only psychologically but also in their neural substrates (Anderson & Sobel, 2003; Dolcos, LaBar, & Cabeza, 2004; Small et al., 2003). These observations suggest that different brain regions could mediate different dimensions of emotion processing. Furthermore, because the different emotional dimensions are represented in different brain regions in the perception of emotional pictures (Grimm et al., 2006), we suggest that the brain localization results of Nitschke et al. (2006) and Bermpohl et al. (2006) which were based on comparisons of anticipation of negative (low valence and high arousal) images with anticipation of neutral (middle valence and low arousal) images should be interpreted with caution. These studies may be reflecting the activity of a neural network that is involved in anticipation of both negative and high arousal picture. For this reason, in assessing the neural substrate of anticipations associated with a negative valence, it is important that anticipations of negative pictures be compared with anticipations of corresponding positive pictures that have an equivalent level of (high) arousal.

In the present research, we first attempted to determine the neural locus of brain activity associated with anticipation. Next, we tested whether the brain regions reported in previous studies would be active in certain or uncertain anticipations of affective pictures. Finally, we explored the relationship between the brain region associated with affective anticipations and other brain regions, using psychophysiological interaction.