The ability to regulate emotion in accordance with one’s goals is paramount in promoting wellbeing and resilience. While this skill is highly heterogeneous across individuals (Davidson, 2003), it is temporally stable within individuals (Lee, Shackman, Jackson, & Davidson, 2009). In a recent report, the ability to flexibly up- and downregulate emotion according to a situational goal predicted better adjustment to a novel stressful situation one year later (Bonanno, Papa, Lalande, Westphal, & Coifman, 2004). Numerous studies have shown that the volitional regulation of picture-induced negative affect recruits prefrontal cortical (PFC) circuitry, including the ventrolateral and dorsomedial regions (e.g., Eippert et al., 2007; Ochsner et al., 2004; Phan et al., 2005; van Reekum et al., 2007). Most of these studies have found amygdalar activity to covary with regulatory goal, suggesting that this region is a critical downstream target of regulatory efforts. Specifically, BOLD signal in the amygdala increases when negative emotion is upregulated and decreases when it is downregulated (Eippert et al., 2007; Ochsner et al., 2004; Urry et al., 2006; van Reekum et al., 2007). Furthermore, the degree of amygdalar signal change has been shown to be associated with self-reported success in regulation of negative affect (e.g., Eippert et al., 2007; Ochsner et al., 2004).

Electrophysiological and functional magnetic resonance imaging (fMRI) data suggest the amygdala may be an important site of integration of pain- and affective-motivational information. The amygdala responds with greater activation to nociceptive stimuli of different modalities (Bornhovd et al., 2002; Dube et al., 2009; Peyron et al., 2007; but also see Petrovic, Carlsson, Petersson, Hansson, & Ingvar, 2004), where the degree of activation is associated with subjective pain ratings (Bornhovd et al., 2002; Peyron et al., 2007). Regarding its function, poor spatial coding of nociceptive stimuli suggests that the amygdala does not subserve sensory discrimination (Bernard, Huang, & Besson, 1992; Neugebauer, Li, Bird, & Han, 2004). Rather, the amygdala has been shown to mediate the emotional modulation of spinal nociceptive responses to painful electrical stimuli (Roy, Piche, Chen, Peretz, & Rainville, 2009). Furthermore, amygdalar responses to pain are augmented among depressed individuals (Strigo, Simmons, Matthews, Craig, & Paulus, 2008a) and in individuals who report increases in pain unpleasantness following a depressed mood induction (Berna et al., 2010). Together, these studies point to the amygdala as a site where individual differences in affective disposition may also influence pain processing.

A large corpus of data indicates that individual differences in vulnerability to mood and anxiety disorders are associated with dysregulated amygdalar responding during emotion-inducing paradigms (Drabant, McRae, Manuck, Hariri, & Gross, 2009; Etkin et al., 2004). We have demonstrated that the magnitude of BOLD response in the amygdala to a fearful stimulus is stable over time (Johnstone et al., 2005), suggesting that individual differences in amygdalar reactivity are trait-like. Additionally, the extent of negative affect experienced over a month correlates with the degree of amygdalar activation to subliminally presented emotional stimuli a year later (Barrett, Bliss-Moreau, Duncan, Rauch, & Wright, 2007). Trait anxiety and habitual usage of reappraisal also closely predict amygdalar responses to fearful faces (Drabant et al., 2009; Etkin et al., 2004). Collectively, these data suggest functioning of the amygdala, a key target of regulatory attempts during emotion regulation paradigms, reliably reflects trait-like individual differences in affective disposition.

To test whether individual differences in emotion regulation success predict pain regulation success, we tested the same individuals three times over an approximately 3-year period (see Figure 1). Individuals came to the laboratory twice to participate in voluntary emotion regulation tasks, one in which peripheral-physiological data were collected (session 1), and one where neuroimaging data were collected (session 2). Individuals returned a third time to the laboratory to participate in a voluntary pain regulation task when neuroimaging, peripheral-physiological and behavioral data were collected (session 3). We hypothesized that individuals with greater ability to regulate negative emotion would also be more successful when regulating their responses to painful stimuli. Given that affect regulation and the emotional modulation of pain both target the amygdala, we further hypothesized that changes in amygdalar activity following regulation would reflect individual differences in regulatory success in both emotion and pain domains.

As individual differences in emotion regulation have been shown to be stable over time (Lee et al., 2009), in this longitudinal study we conducted the psychophysiological (first) and the neuroimaging (second) emotion regulation sessions on average 1.3 years apart, whereas the pain regulation session (third) took place 2.9 years following the psychophysiological emotion regulation session. Participants used cognitive reappraisal as the strategy to modify their responses to negative visual stimuli in both emotion regulation sessions and to nociceptive thermal stimuli in the pain regulation session (Figure 1). Cognitive reappraisal involves voluntarily changing the meaning of an emotion-eliciting event according to a regulatory goal (Gross, 1998) and has been widely demonstrated to alter the experience of emotion, manifested by changes in subjective ratings, facial expression (Gross, 1998) and peripheral-physiological output (Jackson, Malmstadt, Larson, & Davidson, 2000). In all three sessions participants were instructed to either decrease (“suppress”) or increase (“enhance”) their emotional responses to the aversive stimuli by imagining a better or worse outcome associated with them.

To maximize our ability to detect amygdalar changes following regulation, regulatory success was computed as the difference score between responses in the enhance and suppress conditions. A larger score therefore indicates a greater ability to volitionally regulate responses to the aversive stimuli (Bonanno et al., 2004). The adoption of this difference-score approach between two active conditions also allows us to control for effort expended during regulation, which has often been confounded in studies that included a passive control condition only (cf. Urry et al., 2006). Corrugator supercilii facial electromyography (EMG), a well-validated index of emotional state (Lang, Greenwald, Bradley, & Hamm, 1993) that also provides a highly reliable estimate of individual differences in emotion regulation (Lee et al., 2009) was collected during the first emotion regulation session, while BOLD fMRI was collected during the second emotion regulation session. During the pain regulation session, we collected BOLD fMRI and pain unpleasantness ratings. Heart rate data were also available for a subset of participants, which were used to further validate the unpleasantness ratings as an index of regulatory success of the pain experience (Rainville, Bao, & Chretien, 2005).

First, we tested the hypothesis that greater emotion regulation success predicted greater pain regulation success by examining whether changes in corrugator EMG collected during the psychophysiological emotion regulation session predicted changes in self-reported pain unpleasantness during the pain regulation session. Second, we tested whether both emotion regulation and pain regulation success were associated with change in amygdalar activity, and whether the neural correlates of regulatory success in the amygdala were consistent across modalities. Third, we investigated the commonality of skill across pain and emotion regulation paradigms at the neural level using an individual-differences approach: Specifically, we tested whether emotion regulation success measured by corrugator EMG predicted degree of amygdalar change during pain regulation. Finally, we tested whether individual differences in the degree of amygdalar change following emotion regulation predicted the degree of amygdalar change following the volitional regulation of pain as well as pain regulation success.

Our results point to a previously unreported commonality between emotion regulatory and pain regulatory success. Prior evidence stemming from various fields has highlighted the frequent co-occurrence of pain and negative affect (Neugebauer et al., 2004; Price, 2000; Wiech & Tracey, 2009). Negative affect deeply permeates both psychopathological and pain states (Price, 2000; Rainville et al., 2005) as is illustrated, for example, by the fact that the anxiolytic effects of benzodiazepines provide pain relief despite their lack of analgesic properties (Dellemijn & Fields, 1994). Thus, skill at volitionally regulating emotions may generalize to pain. We tested this hypothesis using three experimental paradigms that together examined individual ability to reappraise negative emotion and pain. We found that regulatory ability in response to negative pictures predicted success while regulating responses to pain, which suggests that common skills underlie the regulation of both emotion and pain.

Our study further extends previous findings showing that changing the meaning of a negative event impacts functioning of the amygdala. This subcortical region is considered part of the brain’s early appraisal system (LeDoux, 2000), and recent evidence suggests that it tracks a combination of valence and arousal dimensions of one’s subjective experience in response to an emotional stimulus (Winston, Gottfried, Kilner, & Dolan, 2005). Following this rapid tracking, the amygdala recruits behavioral, endocrine and autonomic responses via its efferent projections to brainstem nuclei (LeDoux, 2000; LeDoux, 2000; Winston et al., 2005). Relatedly, direct amygdalar stimulation increases activity of the corrugator muscle (Lanteaume et al., 2007), which is well known to be associated with valence judgments (Lang et al., 1993). Accordingly, amygdalar activity has been known to be sensitive to regulatory goals of increasing and decreasing negative affect as revealed by cognitive-reappraisal paradigms (Ochsner et al., 2004; Phan et al., 2005; Urry et al., 2006; van Reekum et al., 2007), where the extent of change in amygdalar activation during regulation correlates with self-reported changes in arousal and negative affect (e.g., Ochsner et al., 2004). Here, we extended this finding using an objective metric of emotional state, where our participants’ emotion regulatory abilities as measured by corrugator EMG activity were predictive of the degree of change in activity of a left-amygdalar cluster following emotion regulation instruction (Lee et al., 2010).

Notably, we found that emotion regulation success measured by corrugator EMG and left amygdalar activation during emotion regulation were both predictors of the modulation of amygdalar activation that was associated with pain regulation success. As noted earlier, the amygdala has been found to reflect emotion-dependent modulation of spinal nociceptive responses (Roy et al., 2009) and pain unpleasantness (Berna et al., 2010) following negative mood inductions. Here, we found that the degree of change in amygdalar activity while upregulating versus downregulating pain was associated with corresponding changes in subjective pain unpleasantness and heart rate. Of note, we found separate amygdalar clusters associated with regulatory success in the negative picture-induced emotion and in the thermal pain paradigms. Although our whole-brain image acquisition is not ideally suited to support claims regarding the involvement of specific amygdalar nuclei during our tasks, it is possible that sensory modality-specific demands of our paradigms may have primarily engaged different areas of amygdalar reappraisal circuitry. For example, extracellular recordings of neurons located in the central nucleus of the amygdala of rats have demonstrated that the majority of them respond to thermal and mechanical but not visual or auditory stimuli (Bernard et al., 1992; Neugebauer et al., 2004). In contrast, projections from the visual cortex in the monkey have been shown to be primarily to basal and lateral nuclei (Iwai, Yukie, Suyama, & Shirakawa, 1987). Another related possibility is that reappraising noxious thermal stimulation, an intrinsically threatening stimulus, evoked marked arousal processing in the amygdala, which has been shown to be primarily reflected in dorsal nuclei activity (Davis et al., 2010), consistent with the location of the peak in amygdalar BOLD signal associated with pain regulation success. In contrast, the reappraisal of negative images containing varying arousal levels, and the reflection of reappraisal outcome in corrugator EMG, which is known to be particularly sensitive to the valence, rather than arousal, dimension of one’s emotional responding (e.g., Lang et al., 1993), might have contributed to our finding a neural correlate of emotion regulatory success in a more ventral amygdalar region, previously shown to be implicated in valence processing (Davis et al., 2010). Despite our having found separate clusters reflecting amygdalar engagement across these two modalities of negative affect modulation, our finding that skills in reappraising negative emotion predicted the magnitude of change in the activation of the amygdala during pain regulation suggests that an important way in which affective style may influence the processing of pain is via an individual’s ability to effectively modulate appraisal processes that are at least partially reflected in this brain area. The finding that individual differences in degree of modulation of the amygdala during an emotion regulation paradigm strongly predict individual differences in the degree of modulation of amygdalar activity during a pain regulation paradigm further corroborates this idea.

The unusual nature of this study, with independent assessments of regulatory skill following multi-year temporal intervals, provided us with an excellent opportunity to examine the stability of individual differences in affective responding. The fact that our predictions were confirmed despite significant intervals is a strong indicator of the stability of affective style (Davidson, 2003). The amygdala is one of a few regions for which the reliability of hemodynamic responses to emotional stimuli (i.e., fearful faces) has been verified (Johnstone et al., 2005). Our results not only reinforce these findings by providing further evidence of the temporal stability of individual skill in voluntary regulation of negatively valenced emotional experience (Lee et al., 2009), but also indicate they may be extended to the emotional components involved in pain processing via the engagement of the amygdala.

In our current report of trait-like variability in emotion and pain regulation success, we adopted a contrast between two active regulatory conditions (enhance and suppress), which maximized our ability to identify individual differences in change in activity in a known primary neural target of regulation (i.e., the amygdala). While the focus in our analysis was on the amygdala, future work should address common involvement of cortical circuitry in picture-induced emotion regulation and pain regulation, both across active regulation conditions (controlling for cognitive demand), and across the more commonly analyzed contrasts that include a passive control condition. Of note, the ventrolateral prefrontal cortex (VLPFC) has been shown to play a crucial role in the instantiation of top-down control of both emotion (Wager, Davidson, Hughes, Lindquist, & Ochsner, 2008) and pain processing (Salomons, Johnstone, Backonja, Shackman, & Davidson, 2007). Such analyses will shed light on whether circuitry involving the VLPFC is common across similar reappraisal processes of emotion-eliciting information from different modalities.

Two limitations of the current work warrant future research. First, the nociceptive neuronal population in the amygdala is known to be heterogeneous: Although the majority of neurons respond to pain in an excitatory manner, some are inhibitory (Bernard et al., 1992; Neugebauer et al., 2004), which may underlie the amygdalar participation in stress-induced analgesia (Fields, 2000; Fox & Sorenson, 1994). Thus, delineating which neuronal groups in the amygdala are recruited under differential psychological contexts, leading to analgesic or hyperalgesic outcomes, requires further study. Lastly, although the inclusion of only males is a limitation, we previously found no sex differences in the reliability of emotion regulation skills as indexed by corrugator, suggesting that the predictive value of individual differences in affective style may be similarly valid across males and females(Lee et al., 2009). Future work should, however, include both females and males.

Supplementary Data