Does the amygdala response correlate with the personality trait ‘harm avoidance’ while evaluating emotional stimuli explicitly?

The heritable temperament trait ‘Harm Avoidance’ (HA) from the psychobiological model of personality [1–3] describes an individuals susceptibility to the feelings of fear and anxiety and his/her tendency to exhibit inhibition behavior [3]. The HA dimension ranges from neurotic introversion (high HA) to stable extraversion (low HA) [4]. It shows a strong positive correlation with neuroticism, a strong negative correlation with extraversion and a weak negative correlation with openness and conscientiousness [5], from the Big Five personality model. A high HA individual is characterized by an enhanced fear of uncertainty, by pessimism, extensive worries, shyness and proneness to fatigue. The HA trait has been demonstrated to be useful in the epidemiology and detection of depressions and anxiety disorders and to be predictive for their severity and treatment outcome [6–9]. Individuals prone to anxiety disorders or depressive states have been found to be more attentive to negative stimuli (attentional bias) and to rate positive and neutral stimuli as less positive (emotional bias) [10–13].

The left and right amygdalae are known to be key nodes in the processing of affective stimuli. Both amygdalae are subdivided into 3 subregions: the laterobasal (LB) amygdala mainly involved in determining the valence (positive or negative) and arousal (strength) of the observed emotion, the superficial (SF) amygdala mainly recruited in directing attention towards affective stimuli and finally the centromedial (CM) amygdala mainly involved in initiating behavioral responses [14–19]. The induced emotional responses are down regulated by cognitive processes in the prefrontal cortex by reappraisal of the stimuli and limiting the attention given to the stimuli [20–22].

The personality traits ‘trait anxiety’, ‘neuroticism’ [10, 23–27] and HA [28] were found to correlate positively with the left and right amygdalae responses to fearful stimuli. These studies used a functional magnetic resonance imaging (fMRI) task in which the emotional stimuli were processed implicitly. More specifically, the volunteers were instructed to focus on the non-emotional stimuli presented following an emotional stimulus [28] or on a non-emotional feature in the presented facial expressions (e.g., color, age or gender) [10, 24–26]. Ball et al. [27] asked their subjects to match faces by their facial expressions. These tasks mainly related individual differences in the attentional bias to amygdalae activation as that the presented emotional information was processed automatically and attracted the attention while it had to be ignored to perform the required task.

In a previous study [29] when trying to relate emotion induced amygdalae activity to the personality trait HA beyond the attentional modulation, the participants were instructed to simply observe attentively positive, negative and neutral stimuli without, performing any emotional or cognitive task. This study was based on an earlier study [30] in which differences in the lateralization of the amygdalae responses to affective stimuli were studied in low, average and high HA females. The volunteers were asked to focus on their emotions elicited while passively viewing the stimuli. This study revealed an increased left lateralized amygdala response to the negative stimuli in the high HA participants while no lateralization of the amygdalae response was observed in the low and average HA participants. Contrary to this, the [29] study revealed a negative correlation between the left amygdala activation and HA during the sustained processing of negative stimuli, probably due to an increased tendency in the high HA participants to shift attention away from the negative stimuli in an attempt to control the induced emotional reaction.

Compared to implicitly processed emotional stimuli, explicitly processed stimuli were found to evoke an increased response in the visual processing areas (the visual cortex, the fusiform gyrus and the associated temporal gyrus) due to the increased attentional load and a more detailed analysis of the stimuli and in the prefrontal cortex due to the increased cognitive control needed to perform the task [20, 31–35]. As a result of these differences in visual processing and cognitive control during the explicit processing of affective stimuli, increased amygdalae responses were observed by some researchers [34] while others observed decreased amygdalae responses [31, 33]. The amygdalae responses were found to be less active during an explicit valence rating task than in a passive viewing task [20, 32] due to an increased top-down control from the prefrontal cortex.

An extension of the correlations between amygdalae activity and HA reported using implicit processing and passive viewing tasks could be hypothesized for explicit processing tasks. However, contrary to the attentional bias which has been consistently revealed in patients with affective disorders and is related to affective personality traits in healthy individuals, the emotional bias during facial recognition has only been reported in patients [36–38] but not in healthy individuals [37, 39, 40]. The observed bias in patients was found to be accompanied by an hyperactivation of both amygdalae while subjects rated negative expressions and an hypoactivation while they rated positive expressions.

In the current study, using fMRI we have tried to relate the activation of the different subregions of the amygdalae during the explicit processing of emotional stimuli to HA. We expected the activation in the LB amygdalae to increase with HA due to an increased sensory input from the visual processing areas while we did not expect to find such a correlation in the SF amygdalae and the CM amygdalae due to the increased cognitive control from the prefrontal and cingulate cortex.

In this study, we hypothesized individual differences, dependent on the participants HA scores in the amygdalae activations observed during the explicit evaluation of emotional stimuli. In the high HA participants, the correlation analyses and the ANOVA revealed an enhanced response to the positive and to the negative stimuli in the left LB amygdala. The LB amygdala is known to be involved in processing of the sensory input coming from the visual cortex and the fusiform gyrus [19]. In high HA individuals, the increased visual input was hypothesized to result from an enhanced attentional bias. It has been shown that an enhanced attention towards facial expressions increases the response in the neural system responsible for the perception and the analysis of stimuli [63–65]. More specifically, an increased attentional load will boost the neural activity in the occipital cortex, the temporal cortex and the fusiform gyrus. In line with the hypothesized attentional bias, our whole-brain correlation analyses revealed a positive correlation between the response to the positive stimuli in the visual cortex and the fusiform gyrus and HA. Moreover, a significantly higher neural activation was observed in the high compared to the low HA participants in the right visual cortex independently of the stimulus valence. These observed differences are in agreement with the results of [66], who reported enhanced visual processing in anxious individuals related to their increased attentional bias as revealed by their eye-tracking results. Supplementary to our results [67], reported individual differences, dependent on the subjects HA scores, in the LB amygdalae connectivity with the visual cortex and fusiform gyrus. These differences in connectivity were most clearly observed in their female subjects.

The ANOVA and correlation analyses failed to reveal any activation difference in the CM and SF amygdalae between the low and high HA participants. The CM amygdalae are involved in the generation of the emotional output while the SF amygdalae are an intermediate station between the input from the visual processing areas and the prefrontal cortex [19]. Both subregions have connections with the prefrontal cortex which were found to correlate with HA [67]. However, these correlations were mainly observed in males. Through these connections, the prefrontal cortex is able to inhibit the neural activity in the CM amygdalae. Current theories hypothesize that emotion regulation and the inhibition of the amygdalae responses to affective stimuli are initiated in the VLPFC and continues over a neural network including the DLPFC, the MCC, the ACC, the insular cortex and the superior temporal cortex [68]. It has been shown that explicitly processing affective stimuli requires an increased cognitive control of the induced emotional responses from these areas [20, 31–35]. Our whole brain results revealed that the neural activity in the prefrontal cortex and the cingulate gyrus differs between the low and high HA participants. In general, the neural activity in the prefrontal cortex was found to be higher in the high HA participants. These findings indicate that these participants had to make more efforts to regulate the induced emotional responses during explicit processing of the affective stimuli. We hypothesized that these increased efforts provided an explanation for the absence of any difference in the behavioral responses between the low and high HA participants. The behavioral results were in line with the behavioral results reported in [40]. In agreement with our whole-brain findings [69], reported increased neural correlates of the inhibition of negative emotional information in subjects at family risk to develop a major depressive disorder.

In clinical populations with an anxiety or depressive disorder, response differences while evaluating emotional stimuli were reported in the insular cortex, ACC, MCC, VLPFC and DLPFC in addition to increased amygdalae activations [70, 71]. Unfortunately, these studies did not assign their findings to the amygdalae subregions. These results suggest that depressive patients or patients with an anxiety disorder do not only have impairments in their emotional responses but also in the cognitive and attentional regulation of these induced responses. Functional connectivity studies revealed that impairments in the down-regulation of the amygdalae responses from the prefrontal cortex could be causal for affective disorders [72–74]. Interestingly [72], was able to show this in females with a major depressive disorder while they where processing negative stimuli as well as positive stimuli. As we excluded subjects with symptoms of an affective disorder or a BDI above 9, it was not possible to relate our findings to clinical symptoms.

The results of the current study are in line with our previous papers [29, 30]. In these papers we reported left lateralized amygdala responses to negative stimuli in high HA females [30] and a correlation between the left amygdala activation while passively watching negative stimuli and HA [29]. Others also reported differences between anxious and non-anxious individuals in their left amygdala responses to negative stimuli [27] or correlations between bilateral amygdalae responses to negative stimuli and HA [28] or anxiety [25]. Etkin et al. [10] revealed a positive correlation between the right amygdala activity and trait anxiety. Unfortunately, these previous studies did not assign their findings to the amygdalae subregions. Although it has been shown that the amygdalae respond to positive stimuli as well [75], most of these studies did not include positive stimuli in their paradigm. The current study seems to indicate similar differences related to trait HA in amygdalae responses in response to positive stimuli as to negative stimuli.

In general, these findings imply that individual differences in the neural responses induced by affective stimuli can be partly explained by individual differences in the personality trait HA. The current study extends these findings to the situation in which the participants had to evaluate the affective stimuli explicitly. While during implicit processing or passive viewing of affective stimuli an enhanced emotional response and attentional control has been observed [28, 29], our new results point at differences in the cognitive control needed to perform the explicit task. In healthy females, this enhanced cognitive processing seems to be sufficient to inhibit increased emotional response. Unfortunately, our subject group did not include healthy females with a very high HA score (above 25). This limited range of HA scores limits the interpretation of our results to low, moderate and high HA females and the findings cannot be extended to healthy females with a very high HA score.

Although lateralization studies revealed that both amygdalae respond to emotional stimuli, the left and right amygdalae are found to be involved in different ways in emotional processing. The left amygdala is hypothesized to be involved in processing the emotional valence and arousal of the stimuli while the right amygdala is involved in the fast detection of emotional content in a stimulus [76, 77]. Given that only the left amygdala response correlated with HA in the current and previous studies [29, 30], our findings seem to indicate that only the processing of the valence and arousal of the affective stimuli is related to HA but not the fast detection of these stimuli.

Remarkably, although the neural response in the left LB amygdala correlated significantly with HA, the underlying response was found to be non-significant. As presented in the plots in Figure 3, an explanation for this is that the left LB amygdala deactivated in the low HA participants while it activated in the high HA participants. The performed T-test evaluated whether the mean response from all participants, independent of their HA score, was significantly different from 0.

The only significant amygdalae response observed was an activation of the left and right SF amygdalae, induced by the negative stimuli. This response did not correlate with HA or differ between the low and high HA participants. The SF amygdala is known to be sub-specialized into directing the attention towards socially relevant stimuli and processing the basic emotion of disgust [19]. We hypothesized these observed responses to be indicative for an increased feeling of disgust induced by the negative stimuli due to the dermatological ailments present in the baby faces, in all participants independent of their HA score. These increased feelings of disgust resulted in an increased response time after viewing a negative stimulus. In line with this interpretation, in [29] we had already reported a significant increase in the feelings of disgust (t(19) = 5.69, p < 0.01) in a similar group of healthy females after viewing the negative stimuli outside the MRI environment.

Some final remark should be made regarding the assignment of the findings to the amygdalae subregions. In the current study, this assignment was done using the probabilistic cytoarchitectonic maps of [57]. Although, these probabilistic maps were specifically designed for use in fMRI studies, some caution should exercised regarding the obtained results. Due to the limited spatial resolution of fMRI images, the performed smoothing step and the correlations between neighboring voxels, the accuracy of the assignment of the clusters observed in the amygydalae to the small subregions is rather limited. However, it would be of interest for studies of the relations between amygdalae activations and personality traits or affective disease states to assign their results to the amygdalae subregions given their different roles in affective processing.

A major limitation of the current study is the limited sample size. The sample size was similar to that used by others in similar studies (e.g., [10]: 17 participants, [27]: 45 participants, [28]: 29 participants and [26]: 20 participants). This limited sample size could have resulted in a lack of power, increasing the chance of reporting false negative results (type II errors) aand false positive results (type I errors) [78]. To make an acceptable balance between the chances for reporting type I and type II errors, we performed Monte Carlo simulations in AlphaSim [60, 61] for each analysis. These simulations revealed rather conservative cluster-extent thresholds in combination with the voxel significance threshold of p ≤ 0.005 selected to look at the whole brain results.

The setup of this study implies some limitations on the scope of our results and conclusions. First of all, the study was exclusively carried out on young, healthy females. An extension of our results and conclusions to younger, older or male subjects is not possible without evidence from further research. Secondly, stimuli similar to the ones in our previous studies were used. These stimuli were adapted to our subject group of young females. Although we have shown in earlier publications that these stimuli elicited the desired emotional responses, further evidence is needed to generalize our conclusions to other types of stimuli (e.g., facial expressions of healthy adults and non-facial stimuli) and other emotions (e.g., anger and anxiety). Thirdly, we were not able to incorporate eye tracking in this study. Due to the absence of such a device, we were not able to check whether all volunteers remained focused on the stimulus presentation.

In this study, we have extended the previously reported relationship between the personality trait HA and the neural activity generated while passively viewing or implicitly processing affective stimuli, to the situation where these stimuli are processed explicitly. The results obtained, pointed in the high HA participants to a higher activity in the visual cortex and facial processing areas and in the prefrontal cortex. The enhanced facial processing boosts the activity in the left LB amygdala, while the increased cognitive control successfully inhibits any increased emotional response in the CM amygdalae in high HA females.

Written informed consent was obtained from the participating volunteers for the publication of this report and any accompanying images.