Problems of emotion processing are core aspects of pediatric bipolar disorder (PBD).1
To understand the pathophysiology underlying these alterations of emotion processing, studies have examined affective responses to emotional stimuli to delineate functional abnormalities in frontolimbic circuitry. Facial stimuli have been used for recruiting activation in brain areas crucial for emotion processing, such as the prefrontal cortex (PFC) and the amygdala.2
For example, a functional magnetic resonance imaging (fMRI) study conducted by Rich et al.3
reported greater ventrolateral PFC (VLPFC) and amygdala activity while subjects tried to evaluate hostility in emotionally neutral faces in patients with PBD compared with the controls (HC).3
In the same study, when attention was directed to nonemotional aspects (estimating the nose width in neutral faces), there were no differences between patients with PBD and HC. Another fMRI study found that passive viewing of happy and angry faces induced greater amygdala activity and reduced VLPFC activity in subjects with PBD relative to HC.4
In a variant of an affective Stroop task, patients with PBD showed greater amygdala activation and decreased PFC activation (at the junction of the VLPFC and the dorsolateral PFC [DLPFC]) for negative words compared with neutral words and also relative to negative words in HC.5
Furthermore, similar to previous findings with patients with PBD,3,4
facial affect recognition in adult euthymic bipolar patients has been associated with reduced activation in the right VLPFC and increased activation in the left amygdala.6
Therefore, there is growing evidence for excessive amygdala activation in PBD in response to emotional stimuli, which is consistent with their clinical pattern of increased emotional reactivity. With regard to prefrontal cortical regions that provide modulatory input to limbic systems, findings have been inconsistent because studies have reported increased3
as well as decreased4–6
VLPFC activation in patients with PBD, perhaps based on differences in behavioral paradigms, clinical state, or treatment status of patient groups.
In addition to the functional neuroimaging abnormalities in the PFC and the amygdala, structural neuro-imaging studies indicate smaller amygdala volumes in patients with PBD relative to HC,7–10
which contrasts with adult studies that have reported larger11,12
amygdala volumes. Larger amygdala in adult studies11,12,15,16
has in fact been hypothesized to result from hypertrophy due to chronic and excessive activation in manic patients.16
Although these findings of altered size, be it larger or smaller, do not necessarily imply intrinsic primary abnormalities in the amygdala, they may correlate with functional abnormalities such as increased activation in response to emotional stimuli, regardless of any dysfunction in PFC input to this limbic structure. Given its central role in assessing emotional valence and arousal to emotional stimuli,17–19
its role in emotion-cognition interface,20
and the morphological and functional abnormalities reported in bipolar disorder, examining alterations in amygdala function in PBD may be essential for understanding neural mechanisms of altered emotion processing in this disorder.
To probe the functional integrity of the PFC and the amygdala, studies of emotion have typically used two different emotional processing paradigms. “Directed” emotional processing involves making deliberate judgments about the intensity or type of affect conveyed in a stimulus. This deliberate evaluation process is believed to directly engage the DLPFC (a center for higher order cognitive control) and the VLPFC (a neocortical area providing higher order control of affective responses) that are believed to exert regulatory control over limbic structures such as the amygdala.17
In contrast, “incidental” processing tasks typically focus conscious attention toward nonaffective stimulus features, such as requiring a judgment about the sex or age of an emotional face. In this context, the DLPFC is often engaged in making cognitive decisions, but performing these paradigms does not seem to engage the VLPFC in evaluating emotional cues or regulating emotional responses in the limbic system. Nonbipolar adults,18,19
adult bipolar patients,21
and adult phobic patients22
showed greater amygdala activation, predominantly on the right side, during incidental than directed processing. The greater activation of the amygdala during incidental emotion processing may represent a neural correlate of automatic emotional responsivity when the VLPFC is not engaged in modulating emotion.18,19
In patients with PBD, as previously mentioned, Rich et al.3
examined the neural activity of emotion processing while focusing attention on emotional evaluation (directed processing) versus nonemotional judgments about neutral faces and reported increased VLPFC and left amygdala activation. The current study builds on this earlier study by directly examining incidental versus directed emotional processing of emotional rather than neutral faces. The block design paradigm consisted of a directed condition with deliberate processing of emotional faces (i.e., deciding whether an emotional face is happy or angry) and an incidental condition with implicit processing of emotional faces (i.e., deciding whether the emotional face is younger or older than 35 years). We included an equal number of angry and happy faces, known to have similar affective arousal levels from previous normative work,23
for both the incidental and directed conditions.
Based on the earlier findings illustrating frontolimbic dysfunction in PBD, and findings from adult bipolar studies using incidental versus directed emotion processing,21
we were primarily interested in the specific contribution of PFC and amygdala disturbances during emotion processing in PBD. The activation patterns in unmedicated patients with PBD and euthymia were compared with those in HC in this study. We hypothesized that the PBD group would have reduced control of automatic emotional responses in incidental processing condition relative to directed processing resulting in greater amygdala activation. Second, we predicted that the higher order systems that modulate emotional responses in the VLPFC24
would show decreased functioning in PBD during directed processing. The directed processing condition therefore served as a probe to test for a loss of top-down control of emotions. Elucidating the degree of relative disturbance in these incidental and directed processes can provide important information about the pathophysiology of emotion processing in PBD and potentially guide treatment development.