Study On The Characteristic And Neural Mechanism Of Error Feedback Procession In Obsessive-compulsive Disorder

Objective Obsessive-compulsive disorder(OCD) is a relatively common, high proportion of chronic illness courses that is often associated obsessions and compulsions. In the past decade, investigations using electrophysiological(event-related potentials, ERP) and functional magnetic resonance imaging(f MRI) have converged to implicate a dysfunctional ’error monitoring system’ in the etiology of OCD. Previous studies on the error monitoring function in OCD and SOC focused mainly on excessive and persistent error-related brain activity in Prefrontal Cortex/Anterior Cingulate Cortex(PFC/ACC) and error-related brain potentials(error-related negative wave, ERN). Increased ERN is even considered as a biomarker or endophenotype of the disorder. The processing of negative performance feedback is a critical component in decision-making that allows for flexible adjustment to optimize behavioral outcomes. However, current FRN studies on external feedback error monitoring in OCD are scarce and controversial.Therefore, the purpose of the present study was to examine the neurobiological basis of external feedback error monitoring in OCD from four levels: behaviour,electroencephalograph,source location analysis and Neural Biochemistry.Methods Study1. A total of 628 undergraduate students completed the Chinese Version of the Padua Inventory-Washington State University Revision(PI-WSUR). We chose 14 students who scored in the upper 10% and 14 students who scored in the lowest 10% without anxiety symptoms as a subclinical OC group(SOC) and a low obsessive-compulsive group(LOC). The students all performed the revised Iowa Gambling Task(IGT). There were no significant differences between the 2 groups in sex,age, handedness, HAMA, HAMD and PI-WSUR scores. We used the behavioral research, event-related potentials(ERP) and standardized low-resolution brain electromagnetic tomography(s LORETA) to track external negative feedback processing and its substrate in the brain. Study2. We chose 20 unmedicated OCD patients students who matched to SOC and LOC group in sex, age, handedness. In particular, the OCD patients exhibited no anxiety or depressive symptoms.We compared the FRN amplitude under loss condition and the the amplitude differences between the loss and win conditions in three groups.And the behavioral and electrophysiological characteristics are also compared between Anxiety and Obsessive-compulsive patients. Study3. We chose 11 OCD patients treated with serotonin reuptake inhibitors and 8 OCD patients treated with serotonin reuptake inhibitors-aripiprazole combination.There were no significant differences between the 2 groups in sex, age, handedness,HAMA,HAMD and Yale–Brown Obsessive Compulsive Scale(Y-BOCS) scores. We compared the FRN amplitude under loss condition and the the amplitude differences between the loss and win conditions in the 2 groups, and explore the influence of dopamine agonists on error feedback processing in OCD.Results Study1. The repeated-measures ANOVA of the netscores in IGT task revealed significant effects for the blocks factor [F(5,130)=2.95,P<0.05] and a block by group interaction effect [F(5,130)=2.77, P=0.05].The simple analysis revealed that no significant main effect for blocks were detected in the SOC subjects [F(5,78)=1.82, P=0.12]. However, there was a significant main effect for blocks in the LOC group [F(5,78)=3.062, P=0.015]. In ERP results, the FRN interaction effect of feedback type and group was significant [F(1,26)=15.42, P<0.01]. This simple analysis of effects revealed that the amplitude differences between the loss and win conditions were larger in the SOC group compared with the LOC group. The SOC group displayed larger FRN loss-win difference waveform amplitude(-7.60±4.57 μ V) than the LOC group(-2.59±3.01μV).We observed that FRN is negatively correlated with netscores in behavioral results in SOC group. The current source density in the anterior prefrontal cortex(a PFC), the intersection between the left frontal pole and the left orbito-frontal cortex(BA10/11), was significantly greater in the SOC group compared with the LOC group(t(26)=4.68, P<0.05). we found an intercorrelation of current source density during the loss condition between the d ACC and a PFC in the LOC subjects but not in the SOC group. Study2. In IGT task, there were no significant block by group interaction effect [F(5,264)=1.23,P=0.29] in SOC、OCD、LOC groups.The simple analysis revealed that no significant main effect for blocks were detected in the SOC and OCD subjects [F(5,78)=1.82,P=0.12;F(5,108)=0.43,P=0.83].However, there was a significant main effect for blocks in the LOC group [F(5,78)=3.062, P=0.015]. In ERP results, the FRN interaction effect of feedback type and group was significant[F(1,96)=5.39, P=0.008]. The amplitude differences between the 3 groups are significant(OCD:6.93±1.19μV, SOC:12.89±1.43μV, LOC:13.76±0.91μV). The FRN loss-win difference waveform amplitude differences between the 3 groups are significan [F(2,96) =4.68, P=0.014](SOC:-6.19±0.91μV,OCD:-3.34±0.76μV, LOC:-2.47 ±0.91μV). The OCD group displayed larger amplitude of the FRN than the AND group[F(2,96) =6.86, P=0.013].Significant correlations were not found between the clinical measures(Y-BOCS) and the FRN amplitude. We observed that the correlation between netscores in behavioral results and FRN in OCD significantly[r=-0.53,P=0.02]. Study3. In IGT task, there were no significant block by group interaction effect[F(5,264)=1.23, P=0.29] in SSRI and SSRIDA groups.The simple analysis revealed that no significant main effect for blocks were detected in the 2 groups [F(1,30)=2.66,P=0.12].The FRN loss-win difference waveform amplitude differences between the 2 groups are significant[F(1,38)=4.77, P=0.04], The SSRIDA group displayed lower SSRI loss-win difference waveform amplitude(-2.078±1.04μV) than the LOC group(-5.06±0.89μV). Significant correlations were not found between the clinical measures(Y-BOCS),the FRN amplitude and behavioral results.Conclusions Study1.We found SOC subjects were impaired in their decision making compared with LOC controls.SOC subjects displayed greater amplitudes of FRN during the presentation of loss feedback and greater FRN amplitude differences between loss and win conditions compared with LOC controls. Importantly, our results confirmed that SOC subjects display larger a PFC activation in response to negative feedback stimuli and a dysfunction in the interaction between a PFC and d ACC during FRN production in SOC,which related to decreased ability of decision making in SOC. Study2. We found OCD subjects were impaired in their decision making in IGT task and displayed greater amplitudes of FRN during the presentation of loss feedback when compared with LOC controls. We demonstrated increased FRN for loss feedback in the OCD group and a negative correlation with the behavior adjustment toward a disadvantageous direction.Our results confirmed that OCD subjects displayed larger FRN amplitudes than AND patients. Study3. The current study demonstrated decreased FRN amplitude differences between loss and win conditions in SSRIDA group compared with SSRI controls.It reflects the regulatory role of DA neurotransmitter system on error feedback processing in OCD.