Our study examined the processing of subliminally presented fearful faces in youths with ADHD and the effects of stimulant medications on this processing. We found that in unmedicated youths with ADHD, right amygdalar hyperactivation was associated with the presentation of the fearful faces. This finding overlaps with that of another recent fMRI study in which ADHD subjects were asked to provide subjective ratings of fear in response to neutral faces.8
Although that task design differed from ours in important ways, both studies suggest that fear processing is associated with amygdalar hyperactivation in ADHD youths. Our study extends these findings by also demonstrating that stimulant medications normalize amygdalar hyperactivation in ADHD youths. This is consistent with an oft-noted clinical response of improved emotional control resulting from the use of stimulant medication.33
A recent positron emission tomography (PET) study described attenuated release of dopamine in the amygdala of patients with ADHD,34
a finding that helps explain why dopaminergic agents such as stimulants may help normalize amygdalar functioning in ADHD patients.
Along with abnormal amygdalar activation, we also found abnormal connectivity between the LPFC and amygdala in unmedicated ADHD participants. Although some studies suggest that the prefrontal cortex (PFC) and in particular, the orbitofrontal cortex, may be involved in the regulation of emotion35, 36
, others suggest a division within the PFC with the medial portion indexing reward and pleasure and the more lateral portion indexing loss and negative affect.11, 37
This functional division of the medial and lateral portions of the PFC was supported by a recent meta-analysis of 87 functional neuroimaging studies involving the PFC.37
The enhanced amygdala–LPFC connectivity in ADHD patients may therefore suggest an over-representation, or amplification, the negative affect associated with fearful faces. Indeed, intense outbursts of negative emotion, such as frustration, are quite common in ADHD youths.38
Similarly, we found that the presentation of fearful faces produced a greater inhibitory effect on the amygdala–LPFC connection in the controls compared with the unmedicated ADHD participants. This difference seemed to be greater in the right amygdala–LPFC connections than on the left, consistent with our main finding of right amygdalar hyperactivation in the unmedicated ADHD sample. Taken together, our findings support the interpretation that anomalous processing of negative stimuli within the amygdala and amygdala–LPFC circuit may underlie the intense, negative emotional reactions often seen in ADHD youths. Subsequent investigations with larger sample sizes and more detailed assessments of behavioral responses to negative stimuli should be able to test this interpretation.
Several limitations of this study merit consideration. First, because ADHD participants were scanned twice and the controls only once, the possibility that practice effects account for some of our findings cannot be excluded. This is unlikely given that the ADHD participants demonstrated amygdalar hyperactivation and practice effects should produce less amygdalar activation, not more. Second, the ADHD participants began the study on stimulant medications and it is therefore possible that our results were the product, not of ADHD, but rather of medication exposure itself. This is also unlikely given our findings that the stimulant medications seem to normalize neural activity. Third, the ADHD participants were not all taking the same stimulant medication. Although stimulant medications overlap considerably in their clinical effects and mechanisms of action, they may nonetheless have different effects on the processing of fearful faces; a larger, follow-up study would be necessary to examine this possibility. Fourth, our sample size was small and thus follow-up study with a larger sample is needed to establish the stability of our findings. Fifth, the threshold between subliminal and supraliminal perception may differ between ADHD youths and controls. Thus, it is possible that for the ADHD youths, the presentation of the fearful faces were, at times, supraliminal whereas for the controls, the presentation of the fearful faces remained subliminal. This is unlikely given that post-scanning questionnaires indicate that the ADHD youths were no more likely than the controls to recall having seen the fearful faces, but this potential confound cannot be fully excluded. Sixth, dynamic causal modeling is dependent on the construction of a priori models of interacting brain regions. For each model, causality (i.e., neural activity in region A causes change in the neural activity of region B) is mathematically specified and statistically tested; however, as with all cross-sectional research, causal vs. correlational links cannot be definitively established.
In conclusion, we have shown increased amygdalar activation in unmedicated youths with ADHD in response to subliminal fearful face processing, as well as the coupling of this increased activation with enhanced connectivity between the amygdala and LPFC. Lastly, our study demonstrates that by altering amygdalar activation and amygdalar–LPFC connectivity, stimulant medications can have a normalizing effect on emotional processing.