Pervasive Competition Between Threat and Reward in the Brain
Pervasive Competition Between Threat and Reward in the Brain
To investigate the interactions between appetitive and aversive processing, we used a task with cues signaling the chance of monetary reward and/or mild aversive shock. Our design allowed us to measure responses during the preparatory/anticipatory delay phase with minimal contamination from other task phases, thus enabling us to probe stimulus-independent processes. SCR data revealed interactions between reward and threat during the delay phase. Imaging data during this phase revealed interactions between reward and threat in several key brain regions, including the midbrain/VTA, striatum, BNST, anterior insula, right MFG and dorsal ACC. Overall, our findings support the competition hypothesis and not the salience hypothesis: when reward and threat were jointly present, reward opposed the effect of threat [(threat vs safe)REWARD <(threat vs safe)NO-REWARD] and threat opposed the effect of reward [(reward vs no-reward)THREAT <(reward vs no-reward)SAFE].
Midbrain structures and the striatum are engaged by appetitive processing (Delgado, 2007; Haber and Knutson, 2010). But recruitment of these regions is not limited to appetitive conditions. They take part in the processing of aversive stimuli (Becerra et al., 2001; Roitman et al., 2005; Brischoux et al., 2009; Matsumoto and Hikosaka, 2009; Baliki et al., 2010), financial losses (Carter et al., 2009), anticipation of mild shocks (Jensen et al., 2003) and aversive learning (Delgado et al., 2008). The engagement of these regions during both positive and negative contexts has led to the idea of their role in 'motivational salience' (Jensen, et al., 2003, 2007; Carter et al., 2009; Metereau and Dreher, 2013). Our findings demonstrated instead that, in our task, simultaneous reward and threat information opposed each other. Together, the findings demonstrated competition during the processing of motivationally salient stimuli of opposite valence. Of note, when presented alone, appetitive and aversive cues evoked delay-phase responses in the midbrain and striatum (Figure 6A).
In the nucleus accumbens, consistent with prior studies (Schultz et al., 1992; Knutson et al., 2001), a main effect of Reward was observed during the delay phase. But, neither a main effect of Threat nor an interaction was observed. The absence of a threat effect was somewhat unexpected given the rodent literature (Schoenbaum and Setlow, 2003; Roitman et al., 2005). Nevertheless, the results are consistent with some studies in humans that did not observe accumbens activation during anticipation of mild shocks (Choi et al. 2012) and aversive pictures (Grupe et al., 2013). Future studies using other types of aversive conditions, such as monetary losses (Carter et al., 2009), are needed to clarify potential interactions between appetitive and aversive processing in this region.
The anterior insula is involved during the processing of negative events, such as cues signaling monetary losses (Knutson and Greer, 2008), as well as the anticipation and experience of aversive stimuli (Paulus and Stein, 2006; Simmons et al., 2006). The anterior insula also has been implicated in risk aversion (Kuhnen and Knutson, 2005). Yet, recent studies have observed activation in this region during appetitive processing, including to cues signaling monetary gains (Samanez-Larkin, et al., 2007; Liu et al., 2011; Padmala and Pessoa, 2011). Furthermore, anterior insula neurons increased responses when monkeys knew they would, or might receive, a reward based on performance (Mizuhiki et al., 2012). Here, we also observed the effect of reward and threat in the bilateral anterior insula during the delay phase (Figure 6A). Critically, threat and reward processing opposed each other when simultaneously presented.
We did not observe a main effect of Threat or an interaction in the amygdala during the delay phase. This null finding is not entirely surprising because, as proposed by Davis et al. (2010), responses in the amygdala may be more closely tied to phasic CS+ stimuli signaling 'fear' or transient cues that signal aversive stimuli (Grupe et al., 2013), as opposed to the periods of temporally extended and less predictable threats. Of note, in our previous study (Choi et al., 2012), as well as in a study by Somerville et al. (2010), greater amygdala responses were not detected during threat monitoring over a temporally extended period.
Another region that is involved in threat processing is the BNST in the basal forebrain, especially during conditions involving temporally extended and/or less predictable threat (Davis et al., 2010; Somerville et al., 2010; Alvarez et al., 2011; Somerville et al., 2013). Intriguingly, studies have also reported the involvement of BNST in appetitive processing (McGinty et al., 2011). This region, which is small and has a complex anatomy, is challenging to investigate with fMRI. Here, we investigated BNST responses based on an anatomical ROI and unsmoothed data. The right BNST was activated by both threat and reward during the delay phase. In addition, a significant interaction was detected there during the delay phase, such that reward and threat traded-off against each other.
In the context of aversive processing, the thalamus has been reported to be involved during the anticipation and experience of negative picture stimuli (Herwig et al., 2007; Goldin et al., 2008), anticipation of mild aversive shocks (Choi et al., 2012) and pain processing (Casey, 1999). At the same time, however, the thalamus participates in appetitive motivational circuits together with striatal and midbrain regions (Kalivas and Nakamura, 1999). The involvement of the thalamus in appetitive processing is further supported by human imaging studies with monetary incentives (Knutson et al., 2001; Galvan et al., 2005; Engelmann et al., 2009) and related studies in non-human animals (Gaffan and Murray, 1990; Balleine, 2005; Minamimoto et al., 2005). In the current study, delay-phase responses in the thalamus were observed during threat as well as reward (Figure 6A). In addition, we observed a significant interaction between reward and threat during the delay phase where reward and threat competed against each other when presented simultaneously.
The dorsal ACC participates in both appetitive and aversive processing, especially during goal-directed behaviors, suggesting that it plays an important function in 'adaptive control' (Rushworth and Behrens, 2008; Shackman et al., 2011). Many studies have reported dorsal ACC responses to reward (Shima and Tanji, 1998; Bush et al., 2002; Shidara and Richmond, 2002) and threat (Ploghaus et al., 1999; Etkin et al., 2011) stimuli. Here, dorsal ACC responses during the delay phase revealed simple effects of reward (vs no-reward during the safe condition) and threat (vs safe during the no-reward condition). Again, a competitive interaction between reward and threat was observed during the delay phase.
Whereas the dorsolateral PFC is important for cognition in general, it also has been proposed to be an important convergence site for the integration of both motivation and cognition (Watanabe, 1996; Leon and Shadlen, 1999; Kobayashi et al., 2002) and emotion and cognition (Gray et al., 2002; Erk et al., 2007). In a consistent fashion, here we observed an interaction between reward and threat processing in the right MFG during the delay phase such that reward and threat traded-off against each other.
We also observed a trade-off interaction in the FEF, bilaterally, during the delay phase. In addition, the FEF showed a main effect of Reward. These findings are intriguing because the FEF is important for attention (Kastner and Ungerleider, 2000; Corbetta and Shulman, 2002; Moore and Armstrong, 2003; Armstrong et al., 2006). We interpret the main effect of Reward in terms of attention given that, on seeing the reward cue, participants likely upregulated attention (as indicated by faster RTs). If this interpretation is correct, the counteracting effect of threat on FEF responses suggests that threat might have interfered with attention. In any case, the interaction reveals that reward and threat interact in frontal sites that are important for attention and other related cognitive functions.
Discussion
To investigate the interactions between appetitive and aversive processing, we used a task with cues signaling the chance of monetary reward and/or mild aversive shock. Our design allowed us to measure responses during the preparatory/anticipatory delay phase with minimal contamination from other task phases, thus enabling us to probe stimulus-independent processes. SCR data revealed interactions between reward and threat during the delay phase. Imaging data during this phase revealed interactions between reward and threat in several key brain regions, including the midbrain/VTA, striatum, BNST, anterior insula, right MFG and dorsal ACC. Overall, our findings support the competition hypothesis and not the salience hypothesis: when reward and threat were jointly present, reward opposed the effect of threat [(threat vs safe)REWARD <(threat vs safe)NO-REWARD] and threat opposed the effect of reward [(reward vs no-reward)THREAT <(reward vs no-reward)SAFE].
Midbrain structures and the striatum are engaged by appetitive processing (Delgado, 2007; Haber and Knutson, 2010). But recruitment of these regions is not limited to appetitive conditions. They take part in the processing of aversive stimuli (Becerra et al., 2001; Roitman et al., 2005; Brischoux et al., 2009; Matsumoto and Hikosaka, 2009; Baliki et al., 2010), financial losses (Carter et al., 2009), anticipation of mild shocks (Jensen et al., 2003) and aversive learning (Delgado et al., 2008). The engagement of these regions during both positive and negative contexts has led to the idea of their role in 'motivational salience' (Jensen, et al., 2003, 2007; Carter et al., 2009; Metereau and Dreher, 2013). Our findings demonstrated instead that, in our task, simultaneous reward and threat information opposed each other. Together, the findings demonstrated competition during the processing of motivationally salient stimuli of opposite valence. Of note, when presented alone, appetitive and aversive cues evoked delay-phase responses in the midbrain and striatum (Figure 6A).
In the nucleus accumbens, consistent with prior studies (Schultz et al., 1992; Knutson et al., 2001), a main effect of Reward was observed during the delay phase. But, neither a main effect of Threat nor an interaction was observed. The absence of a threat effect was somewhat unexpected given the rodent literature (Schoenbaum and Setlow, 2003; Roitman et al., 2005). Nevertheless, the results are consistent with some studies in humans that did not observe accumbens activation during anticipation of mild shocks (Choi et al. 2012) and aversive pictures (Grupe et al., 2013). Future studies using other types of aversive conditions, such as monetary losses (Carter et al., 2009), are needed to clarify potential interactions between appetitive and aversive processing in this region.
The anterior insula is involved during the processing of negative events, such as cues signaling monetary losses (Knutson and Greer, 2008), as well as the anticipation and experience of aversive stimuli (Paulus and Stein, 2006; Simmons et al., 2006). The anterior insula also has been implicated in risk aversion (Kuhnen and Knutson, 2005). Yet, recent studies have observed activation in this region during appetitive processing, including to cues signaling monetary gains (Samanez-Larkin, et al., 2007; Liu et al., 2011; Padmala and Pessoa, 2011). Furthermore, anterior insula neurons increased responses when monkeys knew they would, or might receive, a reward based on performance (Mizuhiki et al., 2012). Here, we also observed the effect of reward and threat in the bilateral anterior insula during the delay phase (Figure 6A). Critically, threat and reward processing opposed each other when simultaneously presented.
We did not observe a main effect of Threat or an interaction in the amygdala during the delay phase. This null finding is not entirely surprising because, as proposed by Davis et al. (2010), responses in the amygdala may be more closely tied to phasic CS+ stimuli signaling 'fear' or transient cues that signal aversive stimuli (Grupe et al., 2013), as opposed to the periods of temporally extended and less predictable threats. Of note, in our previous study (Choi et al., 2012), as well as in a study by Somerville et al. (2010), greater amygdala responses were not detected during threat monitoring over a temporally extended period.
Another region that is involved in threat processing is the BNST in the basal forebrain, especially during conditions involving temporally extended and/or less predictable threat (Davis et al., 2010; Somerville et al., 2010; Alvarez et al., 2011; Somerville et al., 2013). Intriguingly, studies have also reported the involvement of BNST in appetitive processing (McGinty et al., 2011). This region, which is small and has a complex anatomy, is challenging to investigate with fMRI. Here, we investigated BNST responses based on an anatomical ROI and unsmoothed data. The right BNST was activated by both threat and reward during the delay phase. In addition, a significant interaction was detected there during the delay phase, such that reward and threat traded-off against each other.
In the context of aversive processing, the thalamus has been reported to be involved during the anticipation and experience of negative picture stimuli (Herwig et al., 2007; Goldin et al., 2008), anticipation of mild aversive shocks (Choi et al., 2012) and pain processing (Casey, 1999). At the same time, however, the thalamus participates in appetitive motivational circuits together with striatal and midbrain regions (Kalivas and Nakamura, 1999). The involvement of the thalamus in appetitive processing is further supported by human imaging studies with monetary incentives (Knutson et al., 2001; Galvan et al., 2005; Engelmann et al., 2009) and related studies in non-human animals (Gaffan and Murray, 1990; Balleine, 2005; Minamimoto et al., 2005). In the current study, delay-phase responses in the thalamus were observed during threat as well as reward (Figure 6A). In addition, we observed a significant interaction between reward and threat during the delay phase where reward and threat competed against each other when presented simultaneously.
The dorsal ACC participates in both appetitive and aversive processing, especially during goal-directed behaviors, suggesting that it plays an important function in 'adaptive control' (Rushworth and Behrens, 2008; Shackman et al., 2011). Many studies have reported dorsal ACC responses to reward (Shima and Tanji, 1998; Bush et al., 2002; Shidara and Richmond, 2002) and threat (Ploghaus et al., 1999; Etkin et al., 2011) stimuli. Here, dorsal ACC responses during the delay phase revealed simple effects of reward (vs no-reward during the safe condition) and threat (vs safe during the no-reward condition). Again, a competitive interaction between reward and threat was observed during the delay phase.
Whereas the dorsolateral PFC is important for cognition in general, it also has been proposed to be an important convergence site for the integration of both motivation and cognition (Watanabe, 1996; Leon and Shadlen, 1999; Kobayashi et al., 2002) and emotion and cognition (Gray et al., 2002; Erk et al., 2007). In a consistent fashion, here we observed an interaction between reward and threat processing in the right MFG during the delay phase such that reward and threat traded-off against each other.
We also observed a trade-off interaction in the FEF, bilaterally, during the delay phase. In addition, the FEF showed a main effect of Reward. These findings are intriguing because the FEF is important for attention (Kastner and Ungerleider, 2000; Corbetta and Shulman, 2002; Moore and Armstrong, 2003; Armstrong et al., 2006). We interpret the main effect of Reward in terms of attention given that, on seeing the reward cue, participants likely upregulated attention (as indicated by faster RTs). If this interpretation is correct, the counteracting effect of threat on FEF responses suggests that threat might have interfered with attention. In any case, the interaction reveals that reward and threat interact in frontal sites that are important for attention and other related cognitive functions.
Source...