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In addiction, there are few human studies on the neural basis of cue-induced changes in value-based decision making (Pavlovian-to-instrumental transfer, PIT). It is especially unclear whether neural alterations related to PIT are due to the physiological effects of substance abuse or rather related to learning processes and/or other etiological factors related to addiction. We have thus investigated whether neural activation patterns during a PIT task help to distinguish subjects with gambling disorder (GD), a nonsubstance-based addiction, from healthy controls (HCs). Thirty GD and 30 HC subjects completed an affective decision-making task in a functional magnetic resonance imaging (fMRI) scanner. Gambling-associated and other emotional cues were shown in the background during the task. Data collection and feature modeling focused on a network of nucleus accumbens (NAcc), amygdala, and orbitofrontal cortex (OFC) (derived from PIT and substance use disorder [SUD] studies). We built and tested a linear classifier based on these multivariate neural PIT signatures. GD subjects showed stronger PIT than HC subjects. Classification based on neural PIT signatures yielded a significant area under the receiver operating curve (AUC-ROC) (0.70, p = 0.013). GD subjects showed stronger PIT-related functional connectivity between NAcc and amygdala elicited by gambling cues, as well as between amygdala and OFC elicited by negative and positive cues. HC and GD subjects were thus distinguishable by PIT-related neural signatures including amygdala-NAcc-OFC functional connectivity. Neural PIT alterations in addictive disorders might not depend on the physiological effect of a substance of abuse but on related learning processes or even innate neural traits.

Objective Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder with a substantial genetic contribution. While the specific variants underlying OCD's heritability are still unknown, findings from genome-wide association studies (GWAS) corroborate the importance of common SNPs explaining the phenotypic variance in OCD. Investigating associations between the genetic liability for OCD, as reflected by a polygenic risk score (PRS), and potential endophenotypes of the disorder, such as the personality trait harm avoidance, may aid the understanding of functional pathways from genes to diagnostic phenotypes. Methods We derived PRS for OCD at severalP-value thresholds based on the latest Psychiatric Genomics Consortium OCD GWAS (2688 cases, 7037 controls) in an independent sample of OCD patients (n = 180), their unaffected first-degree relatives (n = 108) and healthy controls (n = 200). Using linear regression, we tested whether these PRS are associated with the personality trait harm avoidance. Results Results showed that OCD PRS significantly predicted OCD status, with patients having the highest scores and relatives having intermediate scores. Furthermore, the genetic risk for OCD was associated with harm avoidance across the entire sample, and among OCD patients. As indicated by mediation analyses, harm avoidance mediated the association between the OCD PRS and OCD caseness. These results were observed at multipleP-value thresholds and persisted after the exclusion of patients with a current comorbid major depressive or anxiety disorder. Conclusion Our findings support the polygenic nature of OCD and further validate harm avoidance as a candidate endophenotype and diathesis of OCD.

BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

Objective: Attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. The authors sought to directly compare these disorders using structural brain imaging data from ENIGMA consortium data. Methods: Structural T1-weighted whole-brain MRI data from healthy control subjects (N=5,827) and from patients with ADHD (N=2,271), ASD (N=1,777), and OCD (N=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. The authors examined subcortical volume, cortical thickness, and cortical surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults, using linear mixed-effects models adjusting for age, sex, and site (and intracranial volume for subcortical and surface area measures). Results: No shared differences were found among all three disorders, and shared differences between any two disorders did not survive correction for multiple comparisons. Children with ADHD compared with those with OCD had smaller hippocampal volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller intracranial volume than control subjects and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared with adult control subjects and other clinical groups. No OCD-specific differences were observed across different age groups and surface area differences among all disorders in childhood and adulthood. Conclusions: The study findings suggest robust but subtle differences across different age groups among ADHD, ASD, and OCD. ADHD-specific intracranial volume and hippocampal differences in children and adolescents, and ASD-specific cortical thickness differences in the frontal cortex in adults, support previous work emphasizing structural brain differences in these disorders.

No diagnostic biomarkers are available for obsessive-compulsive disorder (OCD). Here, we aimed to identify magnetic resonance imaging (MRI) biomarkers for OCD, using 46 data sets with 2304 OCD patients and 2068 healthy controls from the ENIGMA consortium. We performed machine learning analysis of regional measures of cortical thickness, surface area and subcortical volume and tested classification performance using cross-validation. Classification performance for OCD vs. controls using the complete sample with different classifiers and cross-validation strategies was poor. When models were validated on data from other sites, model performance did not exceed chance-level. In contrast, fair classification performance was achieved when patients were grouped according to their medication status. These results indicate that medication use is associated with substantial differences in brain anatomy that are widely distributed, and indicate that clinical heterogeneity contributes to the poor performance of structural MRI as a disease marker.

Objective: Brain imaging communities focusing on different diseases have increasingly started to collaborate and to pool data to perform well-powered meta- and mega-analyses. Some methodologists claim that a one-stage individual-participant data (IPD) mega-analysis can be superior to a two-stage aggregated data meta-analysis, since more detailed computations can be performed in a mega-analysis. Before definitive conclusions regarding the performance of either method can be drawn, it is necessary to critically evaluate the methodology of, and results obtained by, meta- and mega-analyses. Methods: Here, we compare the inverse variance weighted random-effect meta-analysis model with a multiple linear regression mega-analysis model, as well as with a linear mixed-effects random-intercept mega-analysis model, using data from 38 cohorts including 3,665 participants of the ENIGMA-OCD consortium. We assessed the effect sizes and standard errors, and the fit of the models, to evaluate the performance of the different methods. Results: The mega-analytical models showed lower standard errors and narrower confidence intervals than the meta-analysis. Similar standard errors and confidence intervals were found for the linear regression and linear mixed-effects random-intercept models. Moreover, the linear mixed-effects random-intercept models showed better fit indices compared to linear regression mega-analytical models. Conclusions: Our findings indicate that results obtained by meta- and mega-analysis differ, in favor of the latter. In multi-center studies with a moderate amount of variation between cohorts, a linear mixed-effects random-intercept mega-analytical framework appears to be the better approach to investigate structural neuroimaging data.

Background. Feelings of doubt and perseverative behaviours are key symptoms of obsessive–compulsive disorder (OCD) and have been linked to hyperactive error and conflict signals in the brain. While enhanced neural correlates of error monitoring have been robustly shown, far less is known about conflict processing and adaptation in OCD. Method. We examined event-related potentials during conflict processing in 70 patients with OCD and 70 matched healthy comparison participants, focusing on the stimulus-locked N2 elicited in a flanker task. Conflict adaptation was evaluated by analysing sequential adjustments in N2 and behaviour, i.e. current conflict effects as a function of preceding conflict. Results. Patients with OCD showed enhanced N2 amplitudes compared with healthy controls. Further, patients showed stronger conflict adaptation effects on reaction times and N2 amplitude. Thus, the effect of previous compatibility was larger in patients than in healthy participants as indicated by greater N2 adjustments in change trials (i.e. iC, cI). As a result of stronger conflict adaptation in patients, N2 amplitudes were comparable between groups in incompatible trials following incompatible trials. Conclusions. Larger N2 amplitudes and greater conflict adaptation in OCD point to enhanced conflict monitoring leading to increased recruitment of cognitive control in patients. This was most pronounced in change trials and was associated with stronger conflict adjustment in N2 and behaviour. Thus, hyperactive conflict monitoring in OCD may be beneficial in situations that require a high amount of control to resolve conflict, but may also reflect an effortful process that is linked to distress and symptoms of OCD.

Background. Obsessive–compulsive disorder (OCD) is associated with marked anxiety, which triggers repetitive behaviours or mental rituals. The persistence of pathological anxiety and maladaptive strategies to reduce anxiety point to altered emotion regulation. The late positive potential (LPP) is an event-related brain potential (ERP) that reflects sustained attention to emotional stimuli and is sensitive to emotion-regulation instructions. We hypothesized that patients with OCD show altered electrocortical responses during reappraisal of stimuli triggering their symptoms. Method. To test our hypothesis, ERPs to disorder-relevant, generally aversive and neutral pictures were recorded while participants were instructed to either maintain or reduce emotional responding using cognitive distraction or cognitive reappraisal. Results. Relative to healthy controls, patients with OCD showed enhanced LPPs in response to disorder-relevant pictures, indicating their prioritized processing. While both distraction and reappraisal successfully reduced the LPP in healthy controls, patients with OCD failed to show corresponding LPP modulation during cognitive reappraisal despite successfully reduced subjective arousal ratings. Conclusions. The results point to sustained attention towards emotional stimuli during cognitive reappraisal in OCD and suggest that abnormal emotion regulation should be integrated in models of OCD.

Patienten mit Zwangserkrankung (OCD) weisen selektive Defizite in der Verarbeitung komplexer visueller Informationen sowie im Bereich der Exekutivfunktionen auf, welche sich teilweise auch bei depressiv erkrankten Patienten finden. Das Ziel der Untersuchung bestand darin, kognitive Defizite bei OCD-Patienten zu identifizieren, die ein spezifisches Korrelat der Zwangssymptomatik in Abgrenzung zu Patienten mit unipolarer Depression (MD) darstellen. Vierzig OCD-Patienten, 20 MD-Patienten sowie 40 gesunde Kontrollprobanden wurden hinsichtlich sieben kognitiver Domänen neuropsychologisch untersucht. Innerhalb der OCD-Stichprobe wurden die Leistungen von hoch- und niedrigdepressiven OCD-Patienten nach BDI-Mediansplit (MedianBDI = 15,5) sowie von Patienten mit vs. ohne familiäre Häufung der Erkrankung einander gegenübergestellt. Die OCD-Patienten zeigten Beeinträchtigungen gegenüber Gesunden in allen untersuchten Bereichen bis auf die Domäne „Verbales Gedächtnis“. Die Defizite in den Domänen „Visuelle Organisation“ und „Problemlösen/Arbeitsgedächtnis“ erwiesen sich spezifische Korrelate der Zwangssymptomatik. Die MD-Patienten wiesen ein mit den OCD-Patienten überlappendes Defizit in der Domäne „Verbale Flüssigkeit“ auf. In der OCD-Gruppe korrelierte die Schwere der Zwangsgedanken negativ mit der Domäne „Visuelle Organisation“. Das Ersterkrankungsalter korrelierte negativ mit der Domäne „Visuomotorik/Aufmerksamkeitswechsel“. Es bestand kein bedeutsamer Einfluss der depressiven Begleitsymptomatik sowie der familiären Häufung von OCD auf die kognitiven Leistungen. Anhand dieser Arbeit wurde belegt, dass es sich bei den Defiziten der OCD-Patienten hinsichtlich der visuellen Gestalterfassung sowie der mentalen Manipulation komplexer visueller Information um spezifische Merkmale der Zwangserkrankung in Abgrenzung zu milden Formen unipolarer Depression handelt. Eine leichte depressive Begleitsymptomatik mindert die kognitiven Leistungen von OCD-Patienten nicht zusätzlich., Patients suffering from Obsessive Compulsive Disorder (OCD) show selective deficits both in the processing of complex visual information and regarding executive functions. Patients with Major Depression (MD) were found to have, in parts, similar impairments. The aim of the present study was to identify those cognitive deficits in OCD patients which are a correlate specific to OCD, as opposed to MD patients. We also looked at the influence of the following factors on the cognitive functions of OCD patients: concomitant depression, severity of the disorder, age at onset, and the occurrence of OCD symptoms among immediate family. Forty OCD patients, 20 MD patients, and 40 healthy controls underwent neuropsychological assessment and were compared across seven cognitive domains. For the OCD sample, results of highly and slightly depressive OCD patients, according to BDI median split (medianBDI = 15.5) were compared, as were those of patients with and without a family history of the disorder. OCD patients showed impairments across all domains, not including “Verbal Memory”. The deficits in the domains “Visual Organisation” and “Problem Solving/Working Memory” were found to be specific correlates of obsessive-compulsive symptoms. MD patients had a deficit in “Verbal Fluency” similar to that of OCD patients. Within the OCD group, we found a negative correlation between the current severity of obsessive thoughts and the domain “Visual Organisation”. Age at onset correlated negatively with “Visual Motor Speed/Attentional Set-Shifting”. Neither concomitant depression nor a family history of OCD symptoms influenced cognitive performance significantly. The study proved that the deficits of OCD patients concerning visual organisation and mental manipulation of complex, visually coded information are features specific to this disorder, in delimitation from mild forms of major depression. Concomitant mild forms of depression do not further impair cognitive functions in OCD-patients

Ob es eine 'kritische Periode' beim Spracherwerb gibt oder nicht, wird kontrovers diskutiert. Die Untersuchung zweisprachiger Probanden mit unterschiedlichem Spracherwerbsalter und Sprachleistungsniveau in der Zweitsprache stellt eine gute Möglichkeit dar, diese Frage näher zu beleuchten. In der vorliegenden Studie nutzten wir die funktionelle Magnetresonanztomographie, um den Einfluss der Faktoren Spracherwerbsalter und Sprachleistungsniveau auf die neuronalen Korrelate grammatikalischer und semantischer Verarbeitungsprozesse bei italienisch-deutschsprachigen Probanden mit unterschiedlichem Spracherwerbsalter und Sprachleistungsniveau zu untersuchen. Während das zerebrale Aktivierungsmuster beim semantischen Urteilen größtenteils vom erreichten Sprachleistungsniveau abhängig war, beeinflusste das Spracherwerbsalter hauptsächlich die zerebrale Repräsentation grammatikalischer Verarbeitungsprozesse. Diese Ergebnisse weisen darauf hin, dass beide, das Spracherwerbsalter und das Sprachleistungsniveau, die neuronalen Substrate der Verarbeitung der Zweitsprache beeinflussen, jedoch mit einem unterschiedlichen Effekt auf grammatikalische und semantische Verarbeitungsprozesse., The existence of a 'critical period' for language acquisition is still controversial. Bilingual subjects with variable age of acquisition and proficiency level constitute a suitable model to study this issue. In the present study, we used functional magnetic resonance imaging to investigate the effects of age of acquisition and proficiency level on neural correlates of grammatical and semantic judgments in Italian-German bilinguals who learned the second language at different ages and had different proficiency levels. While the pattern of brain activity for semantic judgment was largely dependent on the proficiency level, the age of acquisition mainly affected the cortical representation of grammatical processes. These findings support the view that both age of acquisition and proficiency level affect the neural substrates of second language processing, with a differential effect on grammar and semantics.