Cognitive Impairments In Patients With Pituitary-Evidence From The ERPs Study

Background:Evidences showed impaired cognitive ability of patients with pituitary adenoma even though cured in image or endocrinology.Therefore,it’s important to explore the characteristic of impaired cognitive ability and underlying neural mechanism.Event-related potentials(ERPs)have been widely used in the early assessment of cognitive functions associated with disease,taking advantage of the high temporal resolution,and then analyzed the characteristics of emotional competence from the perspective of cognitive processing.Sample evidence suggested that the N2nogo amplitude is a valuable measure for response inhibitionas.The Nogo-P3 is generally related to the later stage of the inhibition process that is closely related to the actual conflict inhibition of the motor system.This reflects the non-physiological process of conflict monitoring and inhibitory control in pituitary patients.Mismatch negativity(MMN)is the main biological index of pre-attentive processing.Visual MMN(vMMN)that evoked from facial expressions is known as expression-related Visual MMN(EMMN).It reflects the pre-attentive processing of facial expressions.Therefore,we recorded ERP data using Go/Nogo task to reflect the non-physiological process of conflict monitoring and inhibitory control,and MMN task to reflect probe the physiological mechanism of patients with pituitary adenoma.Method:All patients and control participants had normal or corrected-to-normal visual acuity and sufficient hearing ability.There were 26 patients with PRL pituitary adenoma,GH pituitary adenoma and non-functional pituitary adenoma meeting the above-mentioned conditions(male,11;female,15;27.9±2.8 y).26 healthy volunteers(male,12;female,14;27.2±2.9 y)were selected as the control group.Patients in the control group were in good health,without mental retardation and mental illness,without history of psychoactive substance abuse and family history of mental illness.There was no significant difference in age,gender,educational level and patient group between the two groups(p>.05).一、The dysfunction of inhibition control in Pituitary patients:Evidence from the Go/Nogo ERP study1.1:Stimuli and procedure Visual stimuli(single and double triangles)werepresented in the center of a computer screen(light degree = 60 cd/m2).Participants were seated in a semi-dark room,facing a monitor place 100 cm from their eyes,with a visual angle of 4°×4°.There were 3 blocks with 60 Go(double triangles)and 40 Nogo(single triangle)stimuli for each.The participants were instructed to respond by pressing a button as quickly as possible after the Go stimuli appeared and to withhold the response when the Nogo stimuli appeared.1.2:EEG recording and analysis The electroencephalography(EEG)was recorded from 64-channel array with linked earlobe reference electrodes using Ag/AgCl electrodes mounted in an elastic cap.EEG signals were continuously recorded(band pass 0.05-200Hz,sampling rate 1000Hz)at frontal-central electrode sites(Fz,FCz,Cz;10-20 International System)L3:Statistical analysis The measurements of latencies and amplitudes of N2d and P3d components(measure windows:200-300 ms and 300-600 ms forNd2 and Pd3 components,respectively)were subjected to 2-way repeated measures ANOVA with Site(Fz,FCz,Cz)as within-subject factors and Group(patients,control)as between-subject factor.The degrees of freedom were corrected using the Greenhouse-Geisser epsilon.二、The dysfunction of processing task-irrelevant emotional faces in Pituitary patients:an evidence from expression-related visual MMN2.1:Stimuli and procedure We used deviant-standard-reverse oddball paradigm.The participants were instructed to focus on the center of the display and to detect unpredictable changes in size of the fixation cross("+")in the center of the visual field as accurately as possible,ignoring the faces which appeared on the right and left sides of the fixation cross.2.2EEG recording and analysis The electroencephalography(EEG)was recorded from 64-channel array with linked earlobe reference electrodes using Ag/AgCl electrodes mounted in an elastic cap.EEG signals were continuously recorded(band pass 0.05-200Hz,sampling rate 1000Hz)at occipital-temporal electrode sites(P7,P8,01,02;10-20 International System)2.3Statistical analysis Three-way RMANOVA of early EMMN and late EMMN were calculated for between-group comparisons with factors of the Group(Patients and Controls),Brain region(left and right)and Electrode site TP7/TP8,P7/P8,P07/P08).The P-value was from two-sided statistical tests,and P<0.05 was regarded as statistically significant.ResultPart 11.1:Behavioral data There is behavioral data indicating that RTs in the pituitary adenoma group(365 ms)was similar with that in the control group(370 ms;p =.15).The accuracy did not differ between two groups(95.4%and 96.5%for pituitary adenoma and control groups,respectively;p =.85).1.2ERPs data The ANOVA revealed thatthe Nd2was significantly larger in control group(-1.8μV)that that in patients group(-0.5 μV;F(1,50)=8.8,p<0.01),with faster peak latencies in control group(210 ms)than that in patients group(252 ms;F(1,50)=4.9,p<0.05).Although the Pd3 wasslightly larger in control group(1.7 μV)that that in patients group(1.5p,V;p>0.1),the peak latency ofPd3 was more quickly in control group(310 ms)than that in patients group(360 ms;F(1,50)= 5.2,p<0.05).Part 22.1:There was a significant main effect of Group,F(1,50)= 4.052,p<0.01;partialη2 = 0.51,indicating larger early EMMN in the normal controls(-0.48 μV)than in the depression group(-0.24 μV).The two-way interaction of Group*Expression was significant,F(1,50)= 3.052,p<0.05;partialrη 2 = 0.32,showing that,in the normal group,the expression effect was significant(-0.72 μV and-0.24 μV for sad and happy EMMNs,respectively;p<0.01),whereas the EMMNs did not differ between sad(-0.32 μV)and happy(-0.22 μV;p = 0.72)face conditions in patient group.Conclusion:Part 1There was no significant group difference of behavioral performance,the Nogo effect of N2 component reflecting the conflict monitoring significantly decreased in patients over control group.Moreover,the Pd3 component reflecting conflict inhibition was significantly delayed and slightly smaller in patients.These data indicated that there was a dysfunction of inhibitory control in pituitary adenoma patients.These data suggest the reduced earlier and later stage of inhibitory processes in pituitary individuals,implicating the dysfunction of conflict detection and inhibitory control.Part 2For pituitary adenoma patients,EMMN as an automated information processing index can be derived without the active participation of patients.The EMMN was smaller or absent in the pituitary adenoma patients,as compared with the normal group,which reflected frontal the dysfunction of preattentive processing in the pituitary adenoma group.This study plays an important role in the occurrence and development of affective dysfunction.