While being presented with masked fearful stimuli, our participants showed significant differences in areas that are thought to play a key role in emotion processing, namely the CC and insula. Further, our results suggest a link between family history of MDD and functional anomalies in the Heschl's gyrus.
MDD patients showed reduced activity in the left middle CC when compared to the HC group, adding to previous findings suggesting an important role of CC anomalies in the diagnosis of anxiety disorders and/or depression . In particular, this effect was observed when fearful facial expressions elicited stronger activation, in line with earlier fMRI research suggesting a role for the CC in orienting spatial attention to crude threat signals [8, 17]. In this study, we found no effect in the amygdalae for all participants, suggesting a more direct involvement of the CC in attention recruitment during performance in the dot-probe task. This result might also agree with previous findings showing an involvement of the CC in shaping emotional expectancy in both healthy individuals and patients with MDD . Interestingly, we found no effect in the prefrontal cortex, which contrasts with previous research showing prefrontal anomalies in both MDD and healthy participants with family history of MDD [8, 24, 36]. Our findings might suggest that our version of the dot-probe task is not sensitive to prefrontal activation anomalies in either MDD or FHP subjects, in line with previous research on the dot-probe task showing the involvement of the anterior CC, amygdalae, temporal and occipital cortices [12, 13]. Although these results might need replication, an important consideration is to be made when comparing our data to previous findings in similar experimental contexts: while in the study of Monk et al.  participants were required to consciously shift their attention towards a specific feature of the stimulus presented (that is, participants were asked to rate the size of the nose in a given face), in the dot-probe task, stimulus perception is subliminal (emotional stimuli are masked by neutral stimuli). This might have an effect on how attention is recruited and might explain why, in our study, we detected no prefrontal effect. Previous research [15, 17, 37] has shown that the CC plays a key role in directing attention when an individual is not conscious of an emotional facial stimulus being presented. Further, recent ERP findings suggest that backward masked fearful face-elicited spatial attention facilitates behavior and modulates the early stage of facial processing .
Interestingly, when compared to the FHN group, the FHP group exhibited activation differences in the right Heschl's gyrus. In this area, FHP participants had greater activation for contrast F > N and smaller activation for contrast F < N. The Heschl's gyrus is a subregion of the superior temporal gyrus that, apart from being functionally involved in auditory processing, plays an important role in emotional processing, theory of mind and empathy [39, 40]. Volumetric reductions in this area have been found in MDD patients, even after recovery from the disease . Moreover, similar results have also been shown in bipolar disorder patients . Our results implicate activation differences in superior temporoparietal areas between individuals with and without family history of MDD during exposure to fearful facial expressions. As only the right hemisphere was involved, our findings might also suggest a lateralization effect. This is perhaps in line with previous fMRI research suggesting a role of the right Heschl's gyrus during exposure to emotional (auditory) stimuli  and showing that the activation of auditory processing regions specialized for language, like the Heschl's gyrus, can be detected during performance in tasks requiring visual perception of the human face . This might support the belief that this cortical area plays a role in acquired dynamic audiovisual integration mechanisms in the left superior temporal sulcus . In this context, our results suggest a non-task specific role of the Heschl's gyrus in facial emotion processing, which is perhaps lost in MDD.
It is certainly interesting that MDD patients and FHP participants showed activation anomalies in different cortical areas, when compared to FHN participants. However, in the present study, these two groups consisted of unrelated individuals and whether MDD affects functional aberrances already detected before its onset in FHP subjects should be determined by future longitudinal studies.
The present study has a number of limitations. The subject sample was probably too small to reveal behavioral differences across groups. Additionally, the total number of HC participants was almost double than the number of MDD patients. This surely had an effect on our results. For example, our raw data suggested that MDD patients made considerably more errors than the HC group, although this could not be supported by statistical significance. Increasing the participant sample and having a comparable number of HC versus MDD participants would probably have yielded more definitive results. Further research in a larger sample of participants is also needed to confirm our RT analysis and comparisons (the RTs of some participants were lost due to a system failure).
Importantly, in the present study, we did not include images displaying faces conveying positive (happy) emotions. For this reason, we cannot rule out that our fMRI findings simply reflected brain activation associated with the presentation of emotional stimuli. In this regard, further fMRI research should aim at comparing brain activation relative to both happy and fearful faces. Participants were asked after scanning whether they could recognize subliminal images and confirmed that they did not detect them. Employing a detection task within the session would have been difficult, because participants already had to respond to the dots they saw after the shortly presented face images (100 ms). Further, future studies should also investigate correlations between behavioral and MRI data. Quite a substantial limitation of the present study is also represented by the inclusion of MDD patients with differences in medication which, as shown by previous fMRI research (for example, [23, 45]), can affect brain activation. Finally, it also possible that the outcome of this research was affected by our recruitment method. We selected FHP participants as first-degree relatives of patients with well-known recurrent depression, but who did not necessarily take part in the study. As all the MDD patients recruited were assessed by the same psychiatrists, selecting relatives of MDD patients involved in the study might have contributed to ascertain family history of the disease in FHP participants. On the other hand, this would have introduced a genetic bias, whose selective effect on MRI data should be investigated in future research.