Impaired error processing in late-„phase psychosis: Four-„year stability and relationships with negative symptoms1. Introduction2. Methods and materials2.1. Participants2.2. Task and materials2.2.1. Symptoms2.2.2. Task2.3. Procedure2.4. EEG recording, processing, and data reduction2.5. Data analysis3. Results3.1. Cross-sectional associations3.2. Four-year stability3.3. Longitudinal associations4. DiscussionConflicts of interestContributorsFundingAcknowledgmentsReferencesImpaired error processing in late-phase psychosis: Four-year stabilityand relationships with negative symptomsDan Fotia,⁎,GregPerlmanb, Greg Hajcakc,AprajitaMohantyc,FeliciaJacksonc, Roman KotovbaDepartment of Psychological Sciences, Purdue University, West Lafayette, IN, United StatesbDepartment of Psychiatry, Stony Brook University, Stony Brook, NY, United StatescDepartment of Psychology, Stony Brook University, Stony Brook, NY, United Statesabstractarticle infoArticle history:Received 29 January 2016Received in revised form 6 May 2016Accepted 9 May 2016Available online 24 May 2016Error processing is impaired in psychosis, and numerous event-related potential studies have found reductions inthe error-related negativity (ERN) and, more recently, the error positivity (Pe). The stability of reduced ERN/Pe inpsychosis, however, is unknown. In a previous cross-sectional report, reduced ERN was associated with negativesymptom severity and reduced Pe with a diagnosis of schizophrenia versus other psychosis. Here, we test the sta-bility of impaired error processing over a four-year follow-up and relationships with subdimensions of negativesymptoms. The ERN and Pe were recorded from individuals with psychotic disorders twice: 79 individuals wereassessed 15 years after first hospitalization, and 69 were assessed at 19 years; 59 (26 with schizophrenia, 33 withother psychotic disorders) had data at both assessments. At 19 years the Pe was blunted in schizophrenia. TheERN and Pe exhibited temporal stab ility over the four years (r = 0.59 and 0.60, respectively). Reduced ERNand Pe correlated with the negative symptom subdimensions of inexpressivity and avolition, respectively, andnot with psychotic or disorganized symptoms. Moreover, 15-year ERN predicted an increase in inexpressivityby year 19. No evidence was found for the reverse: negative symptoms did not predict change in ERN/Pe. Similarto non-clinical samples, the ERN and Pe show impressive four-year stability in late-phase psychosis. The ERN andPe are promising neural measures for capturing individual differences in psychotic disorders, particularly withregard to negative symptomatology. They may prove to be useful clinically for forecasting illness course and astreatment targets.© 2016 Elsevier B.V. All rights reserved.Keywords:EEGERPError-related negativityError positivitySchizophrenia1. IntroductionExecutive function is impaired in schizophrenia (Kerns et al., 2008)and is a proposed cognitive mechanism for poor functioning (Bowieet al., 2008). One key aspect of executive function is error processing,which entails the evaluation of errors as salient events followed by thedynamic a djustment of cognitive control to improve performance(Kerns et al., 2008). Event-related potential (ERP) studies of error pro-cessing in schizophrenia have focused on the error-related negativity(ERN), which occurs 0–100 ms following errors on speeded tasks(Falkenstein et al., 1991; Gehring et al., 19 93) and reflects error-related activation of the anterior cingulate cortex (ACC) (Holroyd andColes, 2002). Numerous studies have observed a blunted ERN in schizo-phrenia (Alain et al., 2002; Bates et al., 2002, 2004; Foti et al., 2012,2013; Horan et al., 2012; Kansal et al., 2014; Kopp and Rist, 1 999;Mathalon et al., 2002; Morris et al., 2006), which is related to poor exec-utive function (Kim et al., 2006). A blunted ERN has also been observedin other psychotic disorders (Foti et al., 2012, 2013; Minzenberg et al.,2014), high-risk in dividuals (Laurens et al., 2010; Perez et al., 2012)and unaffected siblings (Simmonite et al., 2012).Studies have also examined the error positivity (Pe), which peaks200–400 ms following errors. The ERN and Pe track distinct stages oferror processing: early, automatic error detection and later, consciouserror recognition, respectively, (Hughes and Yeung, 2011;Nieuwenhuis et al., 2001). Pe relates to post-error adjustment at thebetween-subjects level (Hajcak et al., 2003), whereas ERN relates totrial-by-trial adjustment (Cavanagh and Shackman, 2015). Initial stud-ies in schizophrenia failed to find group differences in Pe amplitude ver-sus controls ( Alain et a l., 2002; Horan et al., 2012; Kim et al., 2006;Mathalon et al., 2002; Morris et al., 2006), perhaps due to limited sam-ple sizes and signal filters that attenuated the Pe (but not the ERN). Bycontrast, three recent studies have observed a blunted Pe specificallyin schizophrenia, both early (Perez et al., 2012) and later in the courseof illness (Foti et al., 2012; Kansal et al., 2014).The ERN and Pe are promising measures of impaired error process-ing, with the ERN reduced in psychotic illness broadly and the Pe re-duced specifically in schizophrenia. Previous studies hav e primarilybeen cross-sectional, however, leaving it unclear how impaired errorSchizophrenia Research 176 (2016) 520–526⁎ Corresponding author at: Department of Psychological Sciences, Purdue University,703 Third Street, West Lafayette, IN 47907, United States.E-mail address: [email protected] (D. Foti).http://dx.doi.org/10.1016/j.schres.2016.05.0090920-9964/© 2016 Elsevier B.V. All rights reserved.Contents lists available at ScienceDirectSchizophrenia Researchjournal homepage: www.elsevier.com/locate/schresprocessing relates to course of illness. In non-clinical samples, the ERNand Pe are highly stable, (Weinberg and Hajcak, 2011). Similarly hightemporal stability among patients would indicate chronic neural deficitsrather than indicators of current clinical state. In this case, it is possiblethat reduced ERN/Pe amplitudes may relate to long-term illness course.On the other hand, if the ERN and Pe fluctuate over time in patients(i.e., show low temporal stability), this would raise the question ofwhat is responsible for fluctuations over time (e.g., whether changesin ERN/Pe amplitudes map onto concurrent changes in symptoms andfunctioning). In one study, ERN amplitude partially normalized follow-ing antips ychotic