The Electrophysiological Mechanism Of Impaired Cognitive Flexibility In Patients With Major Depressive Disorder

Objective:To measure the cognitive flexibility of patients with major depressive disorder(MDD),behavioral measurements and event-related potentials(ERPs)were combined to explore the specific pattern of cognitive flexibility impairment in patients with MDD and its electrophysiological mechanism.Methods:A total of 67 MDD patients and 68 health control subjects(HCs)were enrolled in this study.A series of psychological tests like the Center Depression Rating Scale(CES-D),State Anxiety Inventory(SAI),Cognitive Emotion Regulation Questionnaire(CERQ)were used to evaluate the mental health status of subjects;the Color Trails Test and the Stroop Color Word Test were performed to evaluate the cognitive characteristics of subjects,such as response inhibition and information processing speed;the non-emotional and emotional task switching paradigm were used to evaluate the cognitive flexibility,in the meanwhile,the event-related potentials during the task switching paradigm were collected.The amplitudes and latencies of early N1,P2,N2 and late P3,PSP in ERPs were extracted,and the microstate indicators during the task switching process were calculated.The group differences in demographic and psychological variables were compared byc~2 test and independent sample t test.The group differences in behavior and ERPs were compared by repeated measurement analysis of variance.Results:(1)There were significant differences in scores of CES-D,SAI,CERQ-M.The scores of MDD group were significantly higher than those of HC group(all p<0.01).(2)There were significant differences between MDD group and HC group in the response time of the Color Trails Test(all p<0.05);in the Stroop Color Word Test,there were significant differences between MDD group and HC group in the number of reading items under the word,color and interference condition(all p<0.05).(3)Behavioral analysis showed that the reaction time of MDD group was significantly longer(p<0.01)and the error rate was significantly higher(p<0.001)compared with HC group in the non-emotional task switching paradigm;there was no significant difference in the reaction time between MDD group and HC group(p=0.16),but the error rate of MDD group was significantly higher(p<0.05)in the emotional task switching paradigm.(4)ERPs time-domain analysis showed that in the non-emotional task switching paradigm,compared with HC group,N1 amplitude was marginally larger(p=0.052),P2,P3 and PSP amplitudes were significantly larger in MDD group(all p<0.05),and latencies of N1,P2 and P3 were significantly longer(all p<0.05),Pd2 latency was marginally shorter(p=0.063).The main effects of N1 latency and P2 latency were significant:N1 latency in switch task was significantly longer than that in repeat task(p<0.05),and P2 latency in switch task was significantly longer than that in repeat task(p<0.05).(5)ERPs time-domain analysis showed that in the emotional task switching paradigm,compared with the HC group,PSP amplitude in MDD group was significantly larger(p<0.05),Nd1 amplitude was significantly smaller(p<0.001),Pd2 latency was marginally longer(p=0.062),Nd2latency was significantly longer(p<0.05).The main effect of P2 amplitude and latency,N2 amplitude and latency,P3 amplitude and PSP amplitude was significant:P2 amplitude in the switch task was significantly larger than that in the repeat task(p<0.01),and N2 latency in the repeat task was significantly longer than that in the switch task(p<0.05),and N2 latency in the repeat task was significantly longer than that in the switch task(p<0.05).P3 amplitude in the switch task was significantly larger than that in the repeat task(p<0.001),and PSP amplitude in the switch task was significantly larger than that in the repeat task(p<0.01).(6)Microstate analysis showed that there were significant differences in the occurrence(p<0.01)and coverage(p<0.05)of microstate 2 between MDD group and HC group under the condition of non-emotional task switching;there were significant differences in the frequency(p<0.01)and coverage rate(p<0.01)of microstate 1 and in the mean duration(p<0.05)of microstate 3,marginally significant differences in the mean duration(p=0.052)of microstate 5 between MDD group and HC group under the condition of emotional task switching.Conclusions:(1)MDD patients had impaired cognitive flexibility,and this impairment was not emotion-specific.(2)Electroencephalogram abnormalities in the early attention stage and late preparation stage of task may be the characteristics of impaired cognitive flexibility in MDD.(3)Inadequate goal updating,impaired ability to inhibit interference,and inadequate task set reconstruction may be the electrophysiological mechanism of impaired cognitive flexibility in MDD patients.