Resting State FMRI And Voxel-Based Morphometry Study On Brain Mechanisms Of Emotional Memory In Patients With Depression

Objective: Depression is a common mood disorder; women are twice as likely to experience major depression as men. However, the neural mechanisms that underlie the cognitive aspects of depression are not clear, and the research results are not consistent. This study discussed the changes of resting-state f MRI and default mode network(DMN), dorsal attention network(DAN), ventral attention network(VAN), frontoparietal control network(FPCN), emotional memory network(EMN) and the changes of brain structure in depression. We analyzed the relationship between brain structure and emotional memory in depressive patients, the relationship between brain structure and the severity of depression. We further explored gender differences in emotional memory and the severity of disease in depression.Methods:(1) 38 first episode of unipolar depression(male 12, female 26) and 38 healthy controls(male 14, female 24) were recruited in study 1. In the second study, 62 first episode of unipolar depression(25 male and 37 female) and 130 healthy controls(61 male, 69 female) were selected.(2) Resting-state f MRI(rs-f MRI) analysis:By using ALFF and ReHo, we analyzed the functional differences between depression and normal control. Using functional connections(FC) to analyze the difference of default network(DMN), dorsal attention network(DAN), the ventral attention network(VAN), frontoparietal control network(FPCS) and emotional memory network(including cognition-emotion control system(CECS) and hippocampus memory system(HCMS)) in depression and health controls.(3) Behavior Analysis:Sixty emotion pictures and sixty neutral pictures were used as experimental materials. The experiment was divided encoding and immediately extracted two parts. Behavioral results were record.(4) VBM(morphometry voxel-based): In this study, VBM was used to detect the difference of brain gray matter density changing in AAL116 brain regions between depression and controls, especially in amygdala, hippocampus and prefrontal cortex that associated with emotional memory. Combined behavioral and VBM methods, we detected emotional memory and brain gray matter density to investigate the morphological changes in brain structure in patients with depression; brain areas that related with emotional memory and gender differences were analyzed in depression and controls; the correlation between the severity of depression and brain density were analyzed, gender differences were also explored.Results:(1) Decreased mf ALFF in bilateral precuneus, left superior frontal gyrus / dorsolateral prefrontal cortex, left supplementary motor area and paracentral lobule was found in depression(P < 0.001). Increased mf ALFF was found in left calcarine gyrus, right angular gyrus, right parahippocampal gyrus, bilateral supramarginal gyrus, left cuneus and left middle cingulate gyrus in depression(P < 0.001).(2) Decreased Re Ho in right middle frontal gyrus, right supplementary motor area, right medial superior frontal gyrus, left inferior occipital gyrus, left postcentral gyrus, the right triangular part of inferior frontal gyrus, bilateral superior frontal gyrus / dorsolateral prefrontal cortex, right precentral gyrus and left inferior temporal gyrus was found in depression(P < 0.001). Increased Re Ho was found in bilateral superior temporal pole, bilateral fusiform gyrus, right hippocampus, right middle temporal gyrus, bilateral caudate, left post cingulate gyrus, left middle cingulate gyrus, right precuneus and right superior temporal gyrus in depression(P < 0.001).(3) Direct comparison showed significantly reduced correlation between the DMN and right lingual gyrus, right olfactory, right middle temporal gyrus, left orbital part of inferior frontal gyrus and right supplementary motor area(P < 0.001) in depression compared with controls, while right angular gyrus and right superior temporal gyrus of increased connectivity in the depressed group(P < 0.001).(4) Compared with healthy controls, significantly reduced correlation between the DAN and left middle occipital gyrus, right supplementary motor area was found in depression(P < 0.001), significantly increased connectivity was found between DAN and left opercula part of inferior frontal gyrus, left Rolandic operculum, left insula, left postcentral gyrus, left inferior temporal gyrus, right middle temporal gyrus, right cuneus gyrus and right precuneus(P < 0.001).(5) Direct comparison showed significantly reduced correlation between the VAN and left hippocampus, left lingual gyrus, right olfactory, right parahippocampal and left middle occipital gyrus(P < 0.001) in depression compared with controls, while left Rolandic operculum, left opercula part of inferior frontal gyrus, right middle temporal gyrus, left precentral gyrus, right precuneus, right precentral gyrus and left inferior temporal gyrus of increased connectivity in the depressed group(P < 0.001).(6) Compared with healthy controls, significantly reduced correlation between the FPN and right middle frontal gyrus, left orbital part of middle frontal gyrus and right precentral gyrus was found in depression(P < 0.001), significantly increased connectivity was found between FPN and right precuneus, right superior temporal gyrus and left inferior temporal gyrus(P < 0.001).(7) Direct comparison showed significantly reduced correlation between the EMN and bilateral middle temporal pole, left inferior temporal gyrus, right superior frontal gyrus / dorsolateral prefrontal cortex and right rectus gyrus(P < 0.001) in depression compared with controls, while left caudate, right superior temporal gyrus, right calcarine gyrus and left precentral gyrus of increased connectivity in the depressed group(P < 0.001).(8) Compared with healthy controls, significantly reduced correlation between the HMN and right superior temporal pole, left supplementary motor area and right superior frontal gyrus / dorsolateral prefrontal cortex in depression(P < 0.001), significantly increased connectivity was found between HMN and right insula(P < 0.001).(9) The average reaction time of the neutral pictures and the emotional pictures in depression were higher than those in controls, and the average response rate were lower(p<0.05). There’s no significant difference in emotional memory enhancement effect between two groups(t=1.487, p>0.05). The scores of BDI and HAMD were most highly correlate in depression(r=0.031, p=0.018). The difference between depression and controls was significant(t=-12.52, p=0). The average response rate in emotional pictures and BDI scores showed a significant positive correlation(P < 0.05), while we found no significant correlation between the average response rate in neutral pictures with BDI scores and there’s no significant correlation between emotional memory enhancement effect with BDI scores(P > 0.05).(10) Compared with healthy controls, reduced grey matter density in left superior frontal gyrus, the opercular part of left inferior frontal gyrus, the triangular part of left inferior frontal gyrus, left Rolandic operculum, right rectus gyrus, right ACC, left inferior occipital gyrus, bilateral fusiform gyrus, left Heschl gyrus, right superior temporal pole, left cerebellum Crus1, left cerebellum IV V and right cerebellum VI was found in depression(P < 0.05). Increased grey matter density was found in right calcarine cortex, left putamen, left pallidum, right thalamus, bilateral cerebellum VIII and right cerebellum IX in depression(P < 0.05).(11)In depression, we found positive correlation between emotional memory enhancement(△Pr) and grey matter density in the orbital part of right superior frontal gyrus, right supplementary motor area, right insula, right hippocampus, left parahippocampal, right amygdale, left cuneus, left lingual, right superior occipital gyrus, right fusiform gyrus and right inferior parietal lobule, bilateral superior temporal gyrus, left middle temporal gyrus, bilateral inferior temporal gyrus and bilateral cerebellum Crus2, left cerebellum Crus1 and right cerebellum VI. We didn’t find negative correlation between △Pr and grey matter density in depression. We found negative correlation between △ Pr and grey matter density in female depression in bilateral thalamus, left cerebellum VIII and left cerebellum VIIb, while in male depression we didn’t find negative correlation between △Pr and grey matter density. In healthy control, we found positive correlation between △Pr and bilateral MCC, right superior frontal gyrus and right superior temporal gyrus. We found negative correlation between △Pr and right hippocampus in controls. △Pr had negative correlation with grey matter density in left cerebellum Crus2 in normal female and in right hippocampus in normal male.(12) In depression, we found positive correlation between depressive symptoms(Beck Depression Inventory, BDI) and grey matter density in left precentral gyrus, the orbital part of right inferior frontal gyrus, the triangle part of left inferior frontal gyrus, right middle occipital gyrus, left postcentral gyrus, right supramarginal gyrus, bilateral cerebellum Crus1, left cerebellum VI and left cerebellum VIII. We didn’t find negative correlation between BDI and grey matter density in depression. We found negative correlation between BDI and grey matter density in female depression in bilateral superior frontal gyrus, the orbital part of left superior frontal gyrus, bilateral middle frontal gyrus, the orbital part of bilateral inferior frontal gyrus, the triangle part of right inferior frontal gyrus, right insula, right fusiform gyrus, left inferior parietal, right precuneus, left caudate, left pallidum, right middle temporal gyrus and cerebellum VI, while in male depression we found negative correlation between BDI and grey matter density in left precentral gyrus, orbital part of bilateral superior frontal gyrus, the orbital part of left inferior frontal gyrus, the opercular part of left inferior frontal gyrus, the triangle part of right inferior frontal gyrus, left olfactory, right gyrus rectus, right Rolandic operculum, right ACC, left MCC, left superior parietal lobule, right inferior parietal lobule, right superior temporal gyrus, left superior temporal pole, left inferior temporal gyrus and bilateral cerebellum Crus2.Conclusion:(1) Compared with controls, patients with depression showed significant decrease in cognitive; while the emotional memory enhancement effect still exists. Depressions have negative emotion bias.(2) Extensive abnormal of brain function and brain networks were found in depressive patient in resting state, including emotional memory networks. Both increase brain functional connectivity and decrease brain functional connectivity were existing in each single brain network in depression.(3) Depressions have impaired top-down cognitive control and enhanced bottom-up emotion regulation.(4) Compared with controls, patients with depression showed different abnormal brain subregions in emotional memory enhancement effect, and there is a gender difference.(5) Depression patients have a structural abnormality in the limbic-cortical(including the cerebellar cortex)-striatal-pallidal-thalamic tract(LCSPT).(6) There were brain regions associated with the severity of depression, and there is gender difference.