The goal of this study was to explore differences in neural response to empathy-eliciting stimuli in adolescents with and without aggressive CD. As predicted, when the control participants observed painful situations accidentally caused, regions of the pain matrix were selectively activated, including the insula, aMCC, dorsal ACC, SMA, PAG and somatosensory cortex. This result fits well with previous functional neuroimaging studies on pain empathy (see Jackson, Rainville & Decety, 2006
for a review) that consistently showed that attending to the other people’ pain triggers an automatic somatic sensorimotor resonance mechanism between other and self, which activates almost the entire neural pain matrix in the observer including the periaqueductal gray (PAG) and the SMA.
Interestingly, the pattern of activation in the adolescents with CD showed both similarities as well as striking differences when observing these painful situations. In the CD group, hemodynamic signal increase was detected in the insula, aMCC, SMA, PAG, and somatosensory cortex (see ). In addition, strong activation was observed bilaterally in the amygdala, ventral striatum, and temporal poles. The dorsal portion of the TP projects to the hypothalamus, a neuromodulatory region important for autonomic regulation. Electrical stimulation of the TP produces changes in heart rate, respiration, and blood pressure (Gloor et al., 1982
). These regions (i.e., amygdala, striatum and TP) were not activated in the control participants. This result suggests that individuals with CD actually react to the pain of others to a greater extent than youth without CD. Direct comparison of the two groups further indicates that participants with CD have a stronger signal response in the aMCC, striatum and left amygdala than the control participants when viewing painful situations that have been accidentally caused.
The finding that aggressive adolescents with CD exhibit greater response in the pain matrix when viewing accidental pain than controls is interesting given the finding of previous fMRI studies that reported reduced amygdala response in youth with CD during the viewing of pictures with negative emotional valence (Marsh et al., 2008
; Sterzer et al., 2005
), as well as reduced amygdala volume (Sterzer et al., 2007
). The present findings suggest that youth with CD do not exhibit reduced amygdala response to all negatively valenced stimuli; indeed, they appear to exhibit enhanced response to images of people in pain, including a specific activation of the ventral striatum.
Our results suggest that there may be no deficit in neural response to distress of others (as reflected by the strong activation in the amygdala, temporal poles, and other structures in the pain matrix) in youth with CD. In fact, this somatic sensorimotor resonance was significantly greater (P
< 0.005) in participants with CD than without CD. We also observed that the extent of amygdala activation to painful situations in subjects with CD was significantly related in a positive direction to their number of aggressive acts and ratings of daring and sadism score on the CADS (Lahey et al., in press
The present findings generate at least two hypotheses for testing in future studies. First, it is important to note that the amygdala is involved in the processing of more than just negative affect. Numerous studies point to a role for the amygdala in positive affect, and its coupling with the ventral striatum enables a general arousing effect of reward (Murray, 2007
). It is possible, therefore, that the robust hemodynamic response in the amygdala/ventral striatum to viewing others in pain in youth with aggressive CD reflects a positive affective response (e.g., “excitement”). That is, highly aggressive antisocial youth may enjoy hurting others and, coupled with diminished PFC/amygdala connectivity may not effectively regulate positively reinforced aggressive impulses. The finding that CADS ratings on the daring dimension (which reflects sensation seeking) and sadism items correlate with amygdala response is consistent with this hypothesis. The ventral striatum (nucleus accumbens) plays an important role in reward, pleasure, but also in fear. It is located at the head of the caudate nucleus and anterior portion of the putamen and receives major input (excitatory fibers) from the amygdala and the hippocampal formation. It can be viewed as a functional interface between the limbic and motor systems (Mogenson, Jones & Yim, 1980
). In humans, the striatum is activated by stimuli associated with reward, but also aversive, novel or intense stimuli. A common property linking these stimuli is saliency (Groenewegen, 2007
). Attending to the pain of others may lead to either approach or avoidance. The instrumental aspects of avoidance unlike the Pavlovian elicited responses require connections between the amygdala and the ventral striatum for their acquisition and/or expression. In particular, the nucleus accumbens of the ventral striatum may be a crucial area for the initiation and control of instrumental responses motivated by either appetitive or aversive responses, resulting from its innervation by dopaminergic pathways (LeDoux, 2002
). It is thus difficult to decide whether the amygdala/ventral striatum response in CD participants is associated with enjoyment or repulsion when watching the pain of others. The fact that this condition was also associated with strong activation of the PAG may be a clue. This region of the midbrain receives input from the amygdala and its stimulation triggers aversive or defensive responses and anxiety. It is also worth noting that lesion to the ventral striatum is associated with selective impairment of anger processing, both in the recognition of signals of anger and the experience of this emotion (Calder et al., 2004
Second, many studies indicate that individuals with CD have a lower threshold for sensitivity to negative affect than other youth (Lahey & Waldman, 2003
). This is potentially important as their negative affect may increase the likelihood of aggression, especially in the absence of effective emotion regulation (Berkowitz, 1993
). This interpretation fits well with the hypothesis of a dysfunction in the neural circuitry of emotion regulation (Davidson et al., 2000
) and is consistent with our analyses of effective PFC/amygdala connectivity. Aggression may be related to affective instability and poor impulse control (Raine, 2002
). Children with aggressive behavior problems have difficulties regulating negative emotions, which may result in harmful patterns of interpersonal behavior (Lewis, Granic & Lamm, 2006
). Often triggered by hypersensitivity to specific stimuli, aggressive adults experience escalating agitation followed by an abrupt outburst of aggressive and threatening behavior (Gollan, Lee, & Coccaro, 2005
). Failure to discriminate between pain to others and to oneself may further lead to personal distress. The fact that the anterior TP was specifically and highly activated in youth with CD provides support for the distress interpretation. It has been suggested that the TP is part of a system that modulates visceral functions in response to emotionally evocative stimuli based on its anatomical connectivity (Kondo et al., 2003
). A number of neuroimaging studies have reported activation in the left anterior TP in response to negative visual and auditory stimuli, such as aversive sounds (Olson et al., 2007
). Importantly, one fMRI study found that TP activation correlates with personal distress scores, a measure of how much one personally feels upset when viewing another’s negative emotions (Moriguchi et al., 2006
The stimuli that depicted pain intentionally caused by another individual were associated, in the control group, with additional activation of temporoparietal junction, PCC and lateral OFC. The same pattern of activity was recently reported in a functional MRI study with typically developing children, and interpreted with relation to the perception of social interaction and intentionality (Decety, Michalska & Akitsuki, 2008
). Functional neuroimaging studies have consistently supported the existence of a distributed neural network underlying the ability to understand other people as intentional and emotional agents (theory of mind mechanism). This network comprises the superior temporal sulcus, the TPJ, and the medial prefrontal/anterior paracingulate cortex (e.g., Ciaramidaro et al., 2007
; Decety & Lamm, 2007
). Specifically, research indicates that the anterior PCC is implicated in understanding the mental states of an agent involved in social interaction, regardless of whether this interaction is observed, taking place online or even imagined (e.g., Walter et al., 2004
Different patterns of response were detected in the orbitofrontal cortex across the two groups. While the lateral OFC was selectively activated in the control participants when observing pain inflicted by another, activation of the medial OFC was found in the participants with CD. Direct comparison between the groups confirmed this finding. The OFC/MPFC has been specifically implicated in a variety of areas relevant to CD and aggression, including the regulation of negative affect (Phan et al., 2005
). The finding that the response to these situations in the lateral OFC was attenuated in CD subjects relative to controls suggests an impairment in the CD group in the regulation of negative affect. This interpretation supports the findings of a recent study that observed an attenuated response in this region to angry faces in adults with intermittent explosive disorder (Coccaro et al., 2007
The PPI analyses corroborated the functional MRI findings, demonstrating an amygdala/PFC coupling specifically while watching pain being intentionally caused by another individual and only for the control group. In particular, in healthy adolescents, left amygdala activity covaried with activity in the prefrontal cortex to a greater extent while watching situations of pain being intentionally caused compared to viewing of pain caused by accident. Adolescents with CD showed no functional connectivity between frontal regions and amygdala, which is in line with a recent study that demonstrated greater functional connectivity between the amygdala and PFC in comparison subjects than a group of aggressive youth (Marsh et al., 2008
We posit that the condition in which another individual is inflicting pain intentionally elicits in the normal controls a certain degree of regulation/inhibition. Such regulatory process depends upon posterior STS and medial prefrontal cortex (Harenski & Hamann, 2006
). A meta-analysis shows that frontal regions become active when subjects engage in cognitive strategies (such as reappraisal or detachment) to modulate negative affect (Ochsner & Gross, 2005
). This is consistent with the role of the prefrontal cortex in cognitive inhibition and executive function, processes that are important for the regulation of affect (Fuster, 2001
Overall, our results suggest a complex relation between the neural correlates of empathy and CD. The functional MRI data seem to indicate that adolescents with CD are at least as responsive to the pain of others than the adolescents without CD. The fact that activation of the posterior insula, somatosensory cortex, and PAG are involved in the observation of others in painful situations such an interpretation. However, unlike the adolescents without CD, and the group of typically developing children in our first preliminary study (Decety, Michalska & Akitsuki, 2008
), there was no activation in adolescents with CD in the neural regions that contribute to self-regulation and metacognition (including moral reasoning), such as the DLPFC, PCC, TPJ, dorsal and medial ACC and OFC.
Research with non-humans demonstrates that physical pain often elicits aggression (Berkowitz, 2003
). It has been hypothesized that aggressive persons are disposed to experience negative affect (Anderson & Bushman, 2002
; Lahey & Waldman, 2003
). This suggests that, in certain situations, empathic mimicry might produce high levels of distress in youth predisposed to be aggressive that, ironically, increases their aggression. It is possible that strong activation of neural circuits that underpin actual pain processing is associated with negative affect in youth with CD. This, in conjunction with reduced activation in areas associated with emotion regulation, could result in a dysregulated negative affective state, which may instigate aggression under some circumstances (Berkowitz, 1983
). For example, youth with CD who see an injured friend (or fellow member of a gang) may be more likely to respond aggressively than other youth for this reason.
Finally, the strong and specific activation of the amygdala and ventral striatum in the aggressive adolescents with CD during the perception of pain in others is an important and intriguing finding, which necessitates additional research in order to understand its role in aggression and empathic dysfunction.
This study is to our knowledge the first functional neuroimaging investigation of brain response to pain empathy-eliciting stimuli in aggressive adolescents with CD. In the future it will be important, given the limited size of our sample, to examine whether these findings replicate with larger samples. We believe that such investigations are critical to move beyond self-report measures of empathy. They will also provide a better understanding of the computational and neural mechanism underpinning empathy as well as their dysfunction in high-risk juvenile populations.