Action sequence learning, habits, and automaticity in obsessive-compulsive disorder.

This study investigates the goal/habit imbalance theory of compulsion in obsessive-compulsive disorder (OCD), which postulates enhanced habit formation, increased automaticity, and impaired goal/habit arbitration. It directly tests these hypotheses using newly developed behavioral tasks. First, OCD patients and healthy participants were trained daily for a month using a smartphone app to perform chunked action sequences. Despite similar procedural learning and attainment of habitual performance (measured by an objective automaticity criterion) by both groups, OCD patients self-reported higher subjective habitual tendencies via a recently developed questionnaire. Subsequently, in a re-evaluation task assessing choices between established automatic and novel goal-directed actions, both groups were sensitive to re-evaluation based on monetary feedback. However, OCD patients, especially those with higher compulsive symptoms and habitual tendencies, showed a clear preference for trained/habitual sequences when choices were based on physical effort, possibly due to their higher attributed intrinsic value. These patients also used the habit-training app more extensively and reported symptom relief post-study. The tendency to attribute higher intrinsic value to familiar actions may be a potential mechanism leading to compulsions and an important addition to the goal/habit imbalance hypothesis in OCD. We also highlight the potential of smartphone app training as a habit reversal therapeutic tool.

Altered neural anticipation of reward and loss but not receipt in adolescents with obsessive-compulsive disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is characterized by persistent, unwanted thoughts and repetitive actions. Such repetitive thoughts and/or behaviors may be reinforced either by reducing anxiety or by avoiding a potential threat or harm, and thus may be rewarding to the individual. The possible involvement of the reward system in the symptomatology of OCD is supported by studies showing altered reward processing in reward-related regions, such as the ventral striatum (VS) and the orbitofrontal cortex (OFC), in adults with OCD. However, it is not clear whether this also applies to adolescents with OCD. METHODS: Using functional magnetic resonance imaging, two sessions were conducted focusing on the anticipation and receipt of monetary reward (1) or loss (2), each contrasted to a verbal (control) condition. In each session, adolescents with OCD (n1=31/n2=26) were compared with typically developing (TD) controls (n1=33/ n2=31), all aged 10-19 years, during the anticipation and feedback phase of an adapted Monetary Incentive Delay task. RESULTS: Data revealed a hyperactivation of the VS, but not the OFC, when anticipating both monetary reward and loss in the OCD compared to the TD group. CONCLUSIONS: These findings suggest that aberrant neural reward and loss processing in OCD is associated with greater motivation to gain or maintain a reward but not with the actual receipt. The greater degree of reward 'wanting' may contribute to adolescents with OCD repeating certain actions more and more frequently, which then become habits (i.e., OCD symptomatology).

Hyperactivity of indirect pathway-projecting spiny projection neurons promotes compulsive behavior.

Compulsive behaviors are a hallmark symptom of obsessive compulsive disorder (OCD). Striatal hyperactivity has been linked to compulsive behavior generation in correlative studies in humans and causal studies in rodents. However, the contribution of the two distinct striatal output populations to the generation and treatment of compulsive behavior is unknown. These populations of direct and indirect pathway-projecting spiny projection neurons (SPNs) have classically been thought to promote or suppress actions, respectively, leading to a long-held hypothesis that increased output of direct relative to indirect pathway promotes compulsive behavior. Contrary to this hypothesis, here we find that indirect pathway hyperactivity is associated with compulsive grooming in the Sapap3-knockout mouse model of OCD-relevant behavior. Furthermore, we show that suppression of indirect pathway activity using optogenetics or treatment with the first-line OCD pharmacotherapy fluoxetine is associated with reduced grooming in Sapap3-knockouts. Together, these findings highlight the striatal indirect pathway as a potential treatment target for compulsive behavior.

From compulsivity to compulsion: the neural basis of compulsive disorders.

Compulsive behaviour, an apparently irrational perseveration in often maladaptive acts, is a potential transdiagnostic symptom of several neuropsychiatric disorders, including obsessive-compulsive disorder and addiction, and may reflect the severe manifestation of a dimensional trait termed compulsivity. In this Review, we examine the psychological basis of compulsions and compulsivity and their underlying neural circuitry using evidence from human neuroimaging and animal models. Several main elements of this circuitry are identified, focused on fronto-striatal systems implicated in goal-directed behaviour and habits. These systems include the orbitofrontal, prefrontal, anterior cingulate and insular cortices and their connections with the basal ganglia as well as sensoriomotor and parietal cortices and cerebellum. We also consider the implications for future classification of impulsive-compulsive disorders and their treatment.

Family accommodation in obsessive-compulsive disorder: An updated systematic review and meta-analysis.

Family accommodation might play a crucial role in obsessive-compulsive disorder (OCD). Previous systematic reviews on family accommodation in OCD have focused on specific populations or variables or are outdated. We conducted a preregistered systematic review and meta-analysis on family accommodation in adults, children, and adolescents with OCD (CRD42021264461). We searched PubMed, Scopus, and Web of Science using the keywords "family accommodation" and "obsessive-compulsive disorder. One hundred-eight studies involving 8928 individuals with OCD were included. Our results indicate that levels of family accommodation in OCD are moderate, that there is a significant positive correlation between family accommodation and OCD severity (r = 0.42), that baseline family accommodation does not predict pre- to post-treatment change in OCD severity (g = -0.03), and that family accommodation decreases as a result of both individual and family-focused cognitive behavioral therapy for OCD (g = 2.00 and g = 1.17, respectively). Our findings highlight the relevance of family accommodation in OCD and may help guide assessment and treatment.

Neurocomputational model of compulsivity: deviating from an uncertain goal-directed system.

Despite a theory that an imbalance in goal-directed versus habitual systems serve as building blocks of compulsions, research has yet to delineate how this occurs during arbitration between the two systems in obsessive-compulsive disorder. Inspired by a brain model in which the inferior frontal cortex selectively gates the putamen to guide goal-directed or habitual actions, this study aimed to examine whether disruptions in the arbitration process via the fronto-striatal circuit would underlie imbalanced decision-making and compulsions in patients. Thirty patients with obsessive-compulsive disorder [mean (standard deviation) age = 26.93 (6.23) years, 12 females (40%)] and 30 healthy controls [mean (standard deviation) age = 24.97 (4.72) years, 17 females (57%)] underwent functional MRI scans while performing the two-step Markov decision task, which was designed to dissociate goal-directed behaviour from habitual behaviour. We employed a neurocomputational model to account for an uncertainty-based arbitration process, in which a prefrontal arbitrator (i.e. inferior frontal gyrus) allocates behavioural control to a more reliable strategy by selectively gating the putamen. We analysed group differences in the neural estimates of uncertainty of each strategy. We also compared the psychophysiological interaction effects of system preference (goal-directed versus habitual) on fronto-striatal coupling between groups. We examined the correlation between compulsivity score and the neural activity and connectivity involved in the arbitration process. The computational model captured the subjects' preferences between the strategies. Compared with healthy controls, patients had a stronger preference for the habitual system (t = -2.88, P = 0.006), which was attributed to a more uncertain goal-directed system (t = 2.72, P = 0.009). Before the allocation of controls, patients exhibited hypoactivity in the inferior frontal gyrus compared with healthy controls when this region tracked the inverse of uncertainty (i.e. reliability) of goal-directed behaviour (P = 0.001, family-wise error rate corrected). When reorienting behaviours to reach specific goals, patients exhibited weaker right ipsilateral ventrolateral prefronto-putamen coupling than healthy controls (P = 0.001, family-wise error rate corrected). This hypoconnectivity was correlated with more severe compulsivity (r = -0.57, P = 0.002). Our findings suggest that the attenuated top-down control of the putamen by the prefrontal arbitrator underlies compulsivity in obsessive-compulsive disorder. Enhancing fronto-striatal connectivity may be a potential neurotherapeutic approach for compulsivity and adaptive decision-making.

Mindfulness-based cognitive therapy neurobiology in treatment-resistant obsessive-compulsive disorder: A domain-related resting-state networks approach.

Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes -the precuneus and the frontopolar cortex- were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.

Maximizing translational value in models of compulsive behavior: A commentary on Pickenhan et al. (2024).

In this issue of Cognitive, Affective, and Behavioral Neuroscience, Pickenhan et al. (2024) discuss the need for translational studies to understand features underlying obsessive-compulsive disorder (OCD). They highlight the translational value of the observing-response task (ORT) for modeling functional and maladaptive checking behaviors, a common symptom of OCD.

Compulsive rituals in Obsessive-Compulsive Disorder - A qualitative exploration of thoughts, feelings and behavioral patterns.

BACKGROUND AND OBJECTIVES: Rituals are common among healthy individuals and across cultures and often serve adaptive purposes. In individuals with obsessive-compulsive disorder (OCD), rituals become compulsive, time-consuming and distressing, and may lead to functional impairment. Previous research has examined the functions and characteristics of compulsive rituals, but there is paucity of in-depth, first-person reports about this topic. METHOD: We used a qualitative approach to explore thoughts, feelings, and behavioral patterns that characterize OCD rituals. Ten individuals with OCD participated in a semi-structured interview that focused on their most prominent compulsive ritual. The interviews were subjected to a thematic analysis. RESULTS: Eight themes emerged from the analysis and were organized in two main categories: Micro Level perspective, comprising triggers, attention, emotional changes, and stopping criteria; and Macro Level perspective, comprising feelings and perceptions, change over time, motives, and inhibitors. The findings shed light on the role of fixed rules and feelings of "completeness" in OCD rituals, the nature of emotional and attentional characteristics during rituals performance, and the evolution of compulsive rituals over time. LIMITATIONS: This study used a qualitative approach based on a small number of participants, which limits the generalizability of the findings. CONCLUSION: Our results, if replicated, may have clinical implications. The reported patterns of anxiety reduction during ritual performance may contribute to the fine-tuning of CBT for OCD. The findings concerning the nature of attention during ritual performance and the development of rituals over time may be important for understanding the mechanisms that maintain compulsive rituals.

Externally orienting cues improve cognitive control in OCD.

BACKGROUND AND OBJECTIVES: An executive overload model of obsessive-compulsive disorder (OCD) posits that broad difficulties with executive functioning in OCD result from an overload on the executive system by obsessive thoughts. It implies that, if individuals with OCD "snap out" of their obsessive thoughts, their performance on neurocognitive tasks will improve. METHODS: We test this prediction using the revised Attention Network Test, ANT-R, and distinct subsamples of data from unmedicated OCD and healthy controls (HC). ANT-R includes Simon and Flanker tasks; in both, incongruent trials take longer to resolve ('conflict costs'). On some trials, a warning cue helps participants to respond faster ('alerting benefits'). In OCD (N = 34) and HC (N = 46), matched on age, IQ, and sex, we tested (1) the effect of OCD on alerting benefits, and (2) the effect of OCD on warning cue related reductions in conflict costs. In a distinct subsample of OCD (N = 32) and HC (N = 51), we assessed whether alerting benefits and cue-related reductions in conflict costs are associated differently with different OCD symptoms. RESULTS: A warning cue can help individuals with OCD more than HC to improve performance on Simon and Flanker tasks. This effect is positively associated with severity of contamination symptoms. LIMITATIONS: This study did not directly assess how distracted participants are by obsessive thoughts. It relied on the ANT-R subtraction measures. Symptom severity was assessed using self-report measures. CONCLUSIONS: Difficulties in resolving conflict during decision-making in OCD can be modulated by a warning cue presented immediately before an attentional task.

Dysconnectivity of the Nucleus Accumbens and Amygdala in Youths with Thought Problems: A Dimensional Approach.

Background: Youths with thought problems (TP) are at risk to develop psychosis and obsessive-compulsive disorder (OCD). Yet, the pathophysiological mechanisms underpinning TP are still unclear. Functional magnetic resonance imaging (fMRI) studies have shown that striatal and limbic alterations are associated with psychosis-like and obsessive-like symptoms in individuals at clinical risk for psychosis, schizophrenia, and OCD. More specifically, nucleus accumbens (NAcc) and amygdala are mainly involved in these associations. The current study aims to investigate the neural correlates of TP in youth populations using a dimensional approach and explore potential cognitive functions and neurotransmitters associated with it. Methods: Seed-to-voxels functional connectivity analyses using NAcc and amygdala as regions-of-interest were conducted with resting-state fMRI data obtained from 1360 young individuals, and potential confounders related to TP such as anxiety and cognitive functions were included as covariates in multiple regression analyses. Replicability was tested in using an adult cohort. In addition, functional decoding and neurochemical correlation analyses were performed to identify the associated cognitive functions and neurotransmitters. Results: The altered functional connectivities between the right NAcc and posterior parahippocampal gyrus, between the right amygdala and lateral prefrontal cortex, and between the left amygdala and the secondary visual area were the best predictors of TP in multiple regression model. These functional connections are mainly involved in social cognition and reward processing. Conclusions: The results show that alterations in the functional connectivity of the NAcc and the amygdala in neural pathways involved in social cognition and reward processing are associated with severity of TP in youths.

Intense Imagery Movements May Lead to Maladaptive Daydreaming: A Case Series and Literature Review.

BACKGROUND: This case series highlights the connection between childhood intense imagery movements (IIM) and adult-reported maladaptive daydreaming (MD). Motor stereotypies occur in typically developing children and also with co-occurring neurodevelopmental differences. A subgroup with complex motor stereotypies reports accompanying intense imagery, often enhanced by the movements. This phenomenon can persist into adulthood and, in some cases, will need active management to prevent significant distress and impairment. CASES: Six adults, self-reporting maladaptive daydreaming associated with stereotypies, are presented to demonstrate the associations. LITERATURE REVIEW: The clinical significance and function of IIM and MD are unclear, but several hypotheses are discussed, including the mechanism of emotional regulation through sensory seeking, as a process for processing childhood psychological trauma, as intrusive thoughts or images as part of a subtype of Obsessive Compulsive Disorder, or as a result of diverse attentional networks seen in neurodevelopmental disorders. CONCLUSIONS: This paper highlights important connections between IIM and MD. Many adults with MD show a childhood origin of stereotypical movements. Whilst immersive daydreaming may provide creativity and emotional regulation, there is evidence of distress and impairment of function for some adults, leading to MD diagnoses. Recognizing this phenomenon is important for all neurologists and physicians working with stereotypical movements.

Opening new vistas on obsessive-compulsive disorder with the observing response task.

Obsessive-compulsive disorder (OCD), a highly prevalent and debilitating disorder, is incompletely understood in terms of underpinning behavioural, psychological, and neural mechanisms. This is attributable to high symptomatic heterogeneity; cardinal features comprise obsessions and compulsions, including clinical subcategories. While obsessive and intrusive thoughts are arguably unique to humans, dysfunctional behaviours analogous to those seen in clinical OCD have been examined in nonhuman animals. Genetic, ethological, pharmacological, and neurobehavioural approaches all contribute to understanding the emergence and persistence of compulsive behaviour. One behaviour of particular interest is maladaptive checking, whereby human patients excessively perform checking rituals despite these serving no purpose. Dysfunctional and excessive checking is the most common symptom associated with OCD and can be readily operationalised in rodents. This review considers animal models of OCD, the neural circuitries associated with impairments in habit-based and goal-directed behaviour, and how these may link to the compulsions observed in OCD. We further review the Observing Response Task (ORT), an appetitive instrumental learning procedure that distinguishes between functional and dysfunctional checking, with translational application in humans and rodents. By shedding light on the psychological and neural bases of compulsive-like checking, the ORT has potential to offer translational insights into the underlying mechanisms of OCD, in addition to being a platform for testing psychological and neurochemical treatment approaches.

Temporal dynamics of autonomic nervous system responses under cognitive-emotional workload in obsessive-compulsive disorder.

Dysregulation of the autonomic nervous system (ANS) is commonly observed in various mental disorders, particularly when individuals engage in prolonged cognitive-emotional tasks that require ANS adjustment to workload. Although the understanding of the temporal dynamics of sympathetic and parasympathetic tones in obsessive-compulsive disorder (OCD) is limited, analyzing ANS reactions to cognitive-emotional workload could provide valuable insights into one of the underlying causes of OCD. This study investigated the temporal dynamics of heart rate (HR) and pupil area (PA) while participants with OCD and healthy volunteers solved antisaccade tasks, with affective pictures serving as central fixation stimuli. The data of 31 individuals with OCD and 30 healthy volunteers were included in the study, comprising three separate blocks, each lasting approximately 8 min. The results revealed an increase in sympathetic tone in the OCD group, with the most noticeable rise occurring during the middle part of each block, particularly during the presentation of negative stimuli. Healthy volunteers demonstrated adaptive temporal dynamics of HR and PA from the first block to the last block of tasks, whereas individuals with OCD exhibited fewer changes over time, suggesting a reduced adaptation of the ANS sympathetic tone to cognitive-emotional workload in OCD.

Deep brain stimulation for Tourette syndrome: modulation of the limbic-motor interface network.

OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for medically refractory Tourette syndrome (TS). Several effective targets have been reported, but there is still controversy about the networks involved in the efficacy of DBS for TS. Here, the authors aimed to identify the basal ganglia-thalamo-cortical networks associated with tic and obsessive-compulsive behavior (OCB) improvement and the network link between the two main targets for TS. METHODS: A retrospective analysis of 21 patients treated with pallidal and thalamic DBS was performed. Tics and OCB scores were recorded before and after DBS. The authors localized the electrodes in standard MNI (Montreal Neurological Institute) space and calculated the volume of tissue activated with the settings at the last follow-up to obtain areas of maximal improvement ("sweet spots") among all patients for the pallidal and thalamic targets. Tractography was used to show the white matter pathways associated with maximal tic and OCB improvement. RESULTS: Ten patients treated with pallidal DBS and 11 patients treated with thalamic DBS were included. Responder rates were 80% in the pallidal and 64% in the thalamic target groups. Sweet spots for tics and OCB clustered in several areas across the basal ganglia and thalamus delineated two main networks. Tic reduction in the pallidal target mapped to a limbic pallidothalamic network and in the thalamic target to the premotor thalamocortical network. Putting these two networks together will form the main output of the so-called limbic-motor interface network. However, OCB reduction mapped a dorsomedial prefrontal cortex/dorsal anterior cingulate (dmPFC/dACC) network. CONCLUSIONS: The authors demonstrated the involvement of the limbic-motor interface network during effective DBS for tics in patients with TS. OCB redution was associated with the additional involvement of dmPFC/dACC connections passing dorsal to the head of the globus pallidus pars externa on its way to the thalamus and midbrain.

Astrocyte-neuron subproteomes and obsessive-compulsive disorder mechanisms.

Astrocytes and neurons extensively interact in the brain. Identifying astrocyte and neuron proteomes is essential for elucidating the protein networks that dictate their respective contributions to physiology and disease. Here we used cell-specific and subcompartment-specific proximity-dependent biotinylation1 to study the proteomes of striatal astrocytes and neurons in vivo. We evaluated cytosolic and plasma membrane compartments for astrocytes and neurons to discover how these cells differ at the protein level in their signalling machinery. We also assessed subcellular compartments of astrocytes, including end feet and fine processes, to reveal their subproteomes and the molecular basis of essential astrocyte signalling and homeostatic functions. Notably, SAPAP3 (encoded by Dlgap3), which is associated with obsessive-compulsive disorder (OCD) and repetitive behaviours2-8, was detected at high levels in striatal astrocytes and was enriched within specific astrocyte subcompartments where it regulated actin cytoskeleton organization. Furthermore, genetic rescue experiments combined with behavioural analyses and molecular assessments in a mouse model of OCD4 lacking SAPAP3 revealed distinct contributions of astrocytic and neuronal SAPAP3 to repetitive and anxiety-related OCD-like phenotypes. Our data define how astrocytes and neurons differ at the protein level and in their major signalling pathways. Moreover, they reveal how astrocyte subproteomes vary between physiological subcompartments and how both astrocyte and neuronal SAPAP3 mechanisms contribute to OCD phenotypes in mice. Our data indicate that therapeutic strategies that target both astrocytes and neurons may be useful to explore in OCD and potentially other brain disorders.

Abnormally Enhanced Midfrontal Theta Activity During Response Monitoring in Youths With Obsessive-Compulsive Disorder.

BACKGROUND: Response monitoring, as reflected in electroencephalogram recordings after commission of errors, has been consistently shown to be abnormally enhanced in individuals with obsessive-compulsive disorder (OCD). This has traditionally been quantified as error-related negativity (ERN) and may reflect abnormal neurophysiological mechanisms underlying OCD. However, the ERN reflects the increase in phase-locked activities, particularly in the theta-band (4-8 Hz), and does not reflect non-phase-locked activities. To more broadly investigate midfrontal theta activity in a brain region that is essential for complex cognition, this study investigated theta abnormalities during response monitoring in participants with OCD to acheive a better understanding of the mechanism underlying the ERN. METHODS: Electroencephalogram data were recorded from 99 participants with pediatric OCD and 99 sex- and age-matched healthy control participants while they completed the arrow flanker task. Effects of group (OCD, healthy control) and response type (error, correct) on postresponse theta total power and intertrial phase coherence (ITPC) were examined using mixed analysis of covariance and Bayesian analyses controlling for sex and accuracy. RESULTS: Theta total power was larger on error than on correct trials and larger in OCD than healthy control participants, but there was no effect of response type between groups. Theta ITPC was larger on error than correct trials, but there was no group difference or response type difference between the groups. Correlations of theta total power and ITPC with clinical measures were overall small. CONCLUSIONS: Abnormally enhanced midfrontal theta total power, but not ITPC, may reflect ineffective heightened response monitoring or compensatory activity in pediatric OCD.

P300 and delay-discounting in obsessive-compulsive disorder.

Previous research showed that dysfunctions of fronto-striatal neural networks are implicated in the pathophysiology of obsessive-compulsive disorder (OCD). Accordingly, patients with OCD showed altered performances during decision-making tasks. As P300, evoked by oddball paradigms, is suggested to be related to attentional and cognitive processes and generated in the medial temporal lobe and orbitofrontal and cingulate cortices, it is of special interest in OCD research. Therefore, this study aimed to investigate P300 in OCD and its associations with brain activity during decision-making: P300, evoked by an auditory oddball paradigm, was analysed in 19 OCD patients and 19 healthy controls regarding peak latency, amplitude and source density power in parietal cortex areas by sLORETA. Afterwards, using a fMRI paradigm, Blood-oxygen-level-dependent (BOLD) contrast imaging was conducted during a delay-discounting paradigm. We hypothesised differences between groups regarding P300 characteristics and associations with frontal activity during delay-discounting. The P300 did not differ between groups, however, the P300 latency over the P4 electrode correlated negatively with the NEO-FFI score openness to experience in patients with OCD. In healthy controls, P300 source density power correlated with activity in frontal regions when processing rewards, a finding which was absent in OCD patients. To conclude, associations of P300 with frontal brain activation during delay-discounting were found, suggesting a contribution of attentional or context updating processes. Since this association was absent in patients with OCD, the findings could be interpreted as being indeed related to dysfunctions of fronto-striatal neural networks in patients with OCD.

Co-occurrence of schizo-obsessive traits and its correlation with altered executive control network functional connectivity.

The prevalence of obsessive-compulsive symptoms (OCS) in schizophrenia patients is as around 30%. Evidence suggested that mild OCS could reduce symptoms of schizophrenia, supporting the presence of compensatory functions. However, severe OCS could aggravate various impairments in schizophrenia patients, supporting the "double jeopardy hypothesis". Patients with schizo-obsessive comorbidity, schizophrenia patients and obsessive-compulsive disorder patients have been found to have similarities in executive dysfunctions and altered resting-state functional connectivity within the executive control network (ECN). Executive functions could be associated with the ECN. However, little is known as to whether such overlap exists in the subclinical populations of individuals with schizo-obsessive traits (SOT), schizotypal individuals and individuals with high levels of obsessive-compulsive symptoms (OCS). In this study, we recruited 30 schizotypal individuals, 25 individuals with OCS, 29 individuals with SOT and 29 controls for a resting-state ECN-related functional connectivity (rsFC) and a go/shift/no-go task. We found that individuals with SOT exhibited increased rsFC within the ECN compared with controls, while schizotypal individuals exhibited the opposite. Individuals with OCS exhibited decreased rsFC within the ECN and between the ECN and the default mode network (DMN), relative to controls. No significant correlational results between altered rsFC related to the ECN with executive function performance were found after corrections for multiple comparisons in three subclinical groups. Our findings showed that individuals with SOT had increased rsFC within the ECN, while schizotypal individuals and individuals with OCS showed the opposite. Our findings provide evidence for possible neural substrates of subclinical comorbidity of OCS and schizotypy.

Impaired differential learning of fear versus safety signs in obsessive-compulsive disorder.

Pavlovian learning mechanisms are of great importance both for models of psychiatric disorders and treatment approaches, but understudied in obsessive-compulsive disorder (OCD). Using an established Pavlovian fear conditioning and reversal procedure, we studied skin conductance responses in 41 patients with OCD and in 32 matched healthy control participants. Within both groups, fear acquisition and reversal effects were evident. When comparing groups, patients showed impaired differential learning of threatening and safe stimuli, consistent with previous research. In contrast to prior findings, differential learning impairments were restricted to fear acquisition, and not observed in the reversal stage of the experiment. As previous and present fear reversal experiments in OCD differed in the use of color coding to facilitate stimulus discrimination, the studies converge to suggest that differential learning of threatening versus safe stimuli is impaired in OCD, but manifests itself differently depending on the difficulty of the association to be learned. When supported by the addition of color, patients with OCD previously appeared to acquire an association early but failed to reverse it according to changed contingencies. In absence of such color coding of stimuli, our data suggest that patients with OCD already show differential learning impairments during fear acquisition, which may relate to findings of altered coping with uncertainty previously observed in OCD. Impaired differential learning of threatening versus safe stimuli should be studied further in OCD, in order to determine whether impairments in differential learning predict treatment outcomes in patients, and whether they are etiologically relevant for OCD.