The Neural Pattern Of The Amygdala Activation And Functional Connectivity In Processing Negative Information For The Subjects With Congnitive Vulnerability To Depression

Objective:(1)To examine the activation patterns of the amygdale in subjects with cognitive vulnerability and subjects with major depressive disorder using facial matching task and functional magnetic resonance imaging (fMRI). (2) To examine the patterns of the functional connectivity between the amygdala and other brain regions in subjects with cognitive vulnerability and subjects with major depressive disorder while performing a facial matching task.Methods:(1) Using the cognitive style questionnaire (CSQ) and the Center for Epidemiologic Studies Depression Scale (CESD), we assessed 642 undergraduates in two universities and got 595 subjects with effective data. Computing the weakest scores based on the scores of CSQ and the theory of weakest link, we got subjects with cognitive vulnerability (CV) and healthy control subjects (HC). (2) 29 subjects with CV,33 HC subjects and 32 first-episode treatment-free subjects with major depressive disorder (MDD) from outpatients in the psychology clinic were scanned by fMRI while performing an emotional matching task. (3) Repeated-measures analyses of variance (RM-ANOVA) were used to analyze the accuracy rates and the reaction times (RT) of the subjects when performing the facial matching task. (4) The amygdala was selected as the region of interest (ROI), the activation patterns of the amygdala were examined for those subjects under the facial matching task. Then, the functional connectivity patterns between the amygdala and other brain regions were examined for each group.Results:(1) Psychological measure results:The CESD scores of MDD group were significantly larger than those of either the HC or CV group, while the CESD scores did not reach significantly different between the HC and CV group. The weakest scores of the three groups were significantly different from each other, CV>MDD>HC. (2)Behavioral results of the facial matching task:A significant Group difference for RT was revealed by a RM-ANOVA, and this difference was due to the mean RT of the MDD group being longer than those of the HC group and the CV group. The mean RTs of the HC and CV groups did not differ significantly from each other. We also found a main effect of Type due to the mean RT for matching face being slower than that for matching form. The RM-ANOVA also revealed a significant Type by Group interaction. A conservative Bonferroni post hoc test conducted to reveal the source of this interaction effect showed that mean RTs during the matching face task differed significantly between the groups with MDD subjects reacting slower than HC subjects and CV subjects, and no significant difference between the HC and CV groups. Mean RTs during the matching form task did not differ significantly between the three groups. RM-ANOVA also revealed a significant Type difference for accuracy rate. The accuracy rates for the matching form task were greater than those for the matching face task. There was not a significant group effect or a significant interaction for accuracy rate. (3)The results of activation pattern analysis:Perceptual processing of fearful and angry facial expressions was associated with increased bilateral amygdala activity, relative to the baseline control condition, for each of the three groups. Subjects in all three groups also exhibited significant responses in the dorsolateral prefrontal cortex (DLPFC) as well as occipital gyrus. An ANOVA revealed that there were significant group effects on brain activation elicited by emotional faces relative to baseline activity levels in the frontal lobe, limbic lobe, and sub-lobar region. Post hoc group comparisons highlighted several differences in task-related regional BOLD responses. The left amygdala and right cingulated gyrus showed a greater response in MDD subjects than in HC subjects. Left DLPFC activation was lower in MDD subjects than in HC subjects. A similar pattern was identified with post hoc comparisons between CV and HC subjects, with activity in the bilateral amygdala being significantly greater in CV subjects than in HC subjects and activity in the bilateral dlPFC being greater in HC subjects than in CV subjects. Analysis of the bilateral amygdala response showed that patients with MDD had lower activity in the right amygdala than did CV subjects. To investigate whether the observed amygdala effects were associated with severity of CV, a correlation analysis was performed within the CV group. We found that there was a positive correlation of those subjects with the weakest scores tending to have greater left amygdala responsiveness to threatening faces. (4) The results of functional connectivity pattern analysis:ANOVA showed a significant group effect. The right middle frontal gyrus showed less connectivity with the amygdala in subjects with CV than in HC subjects. The left inferior parietal lobule showed increased connectivity with amygdala in subjects with CV than in HC subjects. A few regions including the left insula, the left cingulated gyrus, bilateral fusiform gyrus showed increased while the left inferior frontal gyrus showed decreased connectivity with amygdala in MDD patients compared with HC subjects. There were significant difference between the MDD and CV group for the connectivity between the left medial frontal gyrus and the amygdala was increased in MDD group compared with CV group. Meanwhile, compared with the right amygdale, the left amygdala showed increased functional connectivity with several regions including the left caudate, the left middle temporal gyrus and the right superior temporal gyrus.Conclusion:(1) The results provide evidence for similar response patterns of the amygdala and prefrontal region to negative emotion stimuli in subjects with CV and MDD. When viewing negative stimuli, individuals with CV and MDD both showed significantly lower activity in the DLPFC and significantly greater activity in the amygdala compared to HC subjects. Besides, the functional connectivity between the amygdale and the prefrontal cortex was decreased for individuals with CV and MDD. (2) The present findings confirm the idea that CV is associated with an automatic negative cognitive bias. The present data also corroborate an earlier finding that MDD compromises an individual’s ability to respond to negative information. (3) The decrease regulation ability originated from the dysfunction of the prefrontal cortex facing negative information might be the neural basis of the vulnerability to depression.