Conflict monitoring and adaptation as reflected by N2 amplitude in obsessive–compulsive disorder

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

Affective evaluation of errors and neural error processing in obsessive-compulsive disorder

Even though overactive error monitoring, indexed by enhanced amplitudes of the error-related negativity (ERN), is a potential biomarker for obsessive-compulsive disorder (OCD), the mechanisms underlying clinical variations in ERN amplitude remain unknown. To investigate whether ERN enhancement in OCD results from altered error evaluation, we examined the trial-wise valence evaluation of errors and its relation to the ERN in 28 patients with OCD and 28 healthy individuals. Electroencephalogram was recorded during an affective priming paradigm in which responses in a go/no-go task were followed by valence-based word categorization. Results indicated that errors were followed by faster categorization of negative than positive words, confirming that negative valence is assigned to errors. This affective priming effect was reduced in patients with OCD, while go/no-go performance was comparable between groups. Notably, this reduction amplified with increasing symptom severity. These results suggest attenuated affective error evaluation in OCD, possibly resulting from interfering effects of anxiety. There was no evidence for a trial-level association between valence evaluation and ERN, implying that ERN amplitude does not reflect valence assignment to errors. Consequently, altered error monitoring in OCD may involve alterations in possibly distinct processes, with weaker assignment of negative valence to errors being one of them.Peer Reviewe

Error-related brain activity as a transdiagnostic endophenotype for obsessive-compulsive disorder, anxiety and substance use disorder

Background Increased neural error-signals have been observed in obsessive-compulsive disorder (OCD), anxiety disorders, and inconsistently in depression. Reduced neural error-signals have been observed in substance use disorders (SUD). Thus, alterations in error-monitoring are proposed as a transdiagnostic endophenotype. To strengthen this notion, data from unaffected individuals with a family history for the respective disorders are needed. Methods The error-related negativity (ERN) as a neural indicator of error-monitoring was measured during a flanker task from 117 OCD patients, 50 unaffected first-degree relatives of OCD patients, and 130 healthy comparison participants. Family history information indicated, that 76 healthy controls were free of a family history for psychopathology, whereas the remaining had first-degree relatives with depression (n = 28), anxiety (n = 27), and/or SUD (n = 27). Results Increased ERN amplitudes were found in OCD patients and unaffected first-degree relatives of OCD patients. In addition, unaffected first-degree relatives of individuals with anxiety disorders were also characterized by increased ERN amplitudes, whereas relatives of individuals with SUD showed reduced amplitudes. Conclusions Alterations in neural error-signals in unaffected first-degree relatives with a family history of OCD, anxiety, or SUD support the utility of the ERN as a transdiagnostic endophenotype. Reduced neural error-signals may indicate vulnerability for under-controlled behavior and risk for substance use, whereas a harm- or error-avoidant response style and vulnerability for OCD and anxiety appears to be associated with increased ERN. This adds to findings suggesting a common neurobiological substrate across psychiatric disorders involving the anterior cingulate cortex and deficits in cognitive control

Temporospatial dissociation of Pe subcomponents for perceived and unperceived errors

Previous research on performance monitoring revealed that errors are followed by an initial fronto-central negative deflection (error-related negativity, ERN or Ne) and a subsequent centro-parietal positivity (error positivity, Pe). It has been shown that error awareness mainly influences the Pe, whereas the ERN seems unaffected by conscious awareness of an error. The aim of the present study was to investigate the relation of ERN and Pe to error awareness in a visual size discrimination task in which errors are not elicited by impulsive responding but by perceptual difficulty. Further, we applied a temporospatial principal component analysis (PCA) to examine whether the temporospatial subcomponents of the Pe would differentially relate to error awareness. Event-related potential (ERP) results were in accordance with earlier studies: a significant error awareness effect was found for the Pe, but not for the ERN. Interestingly, a modulation with error perception on correct trials was found: correct responses considered as incorrect had larger correct-related negativity (CRN) and lager Pe amplitudes than correct responses considered as correct. The PCA yielded two relevant spatial factors accounting for the Pe (latency 300 ms). A temporospatial factor characterized by a centro-parietal positivity varied significantly with error awareness. Of the two temporospatial factors corresponding to ERN and CRN, one factor with central topography varied with response correctness and subjective error perception on correct responses. The PCA results indicate that the error awareness effect is specifically related to the centro-parietal subcomponent of the Pe. Since this component has also been shown to be related to the importance of an error, the present variation with error awareness indicates that this component is sensitive to the salience of an error and that salience secondarily may trigger error awareness

Associations of neural error-processing with symptoms and traits in a dimensional sample recruited across the obsessive–compulsive spectrum

The error-related negativity (ERN), a neural response to errors, has been associated with several forms of psychopathology and assumed to represent a neural risk marker for obsessive–compulsive disorder (OCD) and anxiety disorders. Yet, it is still unknown which specific symptoms or traits best explain ERN variation. This study investigated performance-monitoring in participants (N = 100) recruited across a spectrum of obsessive–compulsive characteristics (n = 26 patients with OCD; n = 74 healthy participants including n = 24 with low, n = 24 with medium, and n = 26 with high OC-characteristics). Several compulsivity- and anxiety-associated characteristics were assessed and submitted to exploratory principal axis factor analysis. Associations of raw measures and derived factors with ERN and correct-related negativity (CRN) were examined. Patients with OCD showed increased ERN amplitudes compared to healthy participants. The ERN was associated with a variety of traits related to anxiety and negative affect. Factor analysis results revealed a most prominent association of the ERN with a composite measure of anxiety and neuroticism, whereas the CRN was specifically associated with compulsivity. Results support differential associations for the ERN and CRN and demonstrate that a dimensional recruitment approach and use of composite measures can improve our understanding of characteristics underlying variation in neural performance monitoring.Peer Reviewe

Gaussian Approximation Potentials: theory, software implementation and application examples

Gaussian Approximation Potentials are a class of Machine Learned Interatomic Potentials routinely used to model materials and molecular systems on the atomic scale. The software implementation provides the means for both fitting models using ab initio data and using the resulting potentials in atomic simulations. Details of the GAP theory, algorithms and software are presented, together with detailed usage examples to help new and existing users. We review some recent developments to the GAP framework, including MPI parallelisation of the fitting code enabling its use on thousands of CPU cores and compression of descriptors to eliminate the poor scaling with the number of different chemical elements

Massively parallel fitting of Gaussian approximation potentials

We present a data-parallel software package for fitting Gaussian approximation potentials (GAPs) on multiple nodes using the ScaLAPACK library with MPI and OpenMP. Until now the maximum training set size for GAP models has been limited by the available memory on a single compute node. In our new implementation, descriptor evaluation is carried out in parallel with no communication requirement. The subsequent linear solve required to determine the model coefficients is parallelised with ScaLAPACK. Our approach scales to thousands of cores, lifting the memory limitation and also delivering substantial speedups. This development expands the applicability of the GAP approach to more complex systems as well as opening up opportunities for efficiently embedding GAP model fitting within higher-level workflows such as committee models or hyperparameter optimisation

Error-related activity of the sensorimotor network contributes to the prediction of response to cognitive-behavioral therapy in obsessive–compulsive disorder

Background Although cognitive behavioral therapy is a highly effective treatment for obsessive–compulsive disorder (OCD), yielding large symptom reductions on the group level, individual treatment response varies considerably. Identification of treatment response predictors may provide important information for maximizing individual treatment response and thus achieving efficient treatment resource allocation. Here, we investigated the predictive value of previously identified biomarkers of OCD, namely the error-related activity of the supplementary motor area (SMA) and the sensorimotor network (SMN, postcentral gyrus/precuneus). Methods Seventy-two participants with a primary diagnosis of OCD underwent functional magnetic resonance imaging (fMRI) scanning while performing a flanker task prior to receiving routine-care CBT. Results Error-related BOLD response of the SMN significantly contributed to the prediction of treatment response beyond the variance accounted for by clinical and sociodemographic variables. Stronger error-related SMN activity at baseline was associated with a higher likelihood of treatment response. Conclusions The present results illustrate that the inclusion of error-related SMN activity can significantly increase treatment response prediction quality in OCD. Stronger error-related activity of the SMN may reflect the ability to activate symptom-relevant processing networks and may thus facilitate response to exposure-based CBT interventions