Atypical action updating in a dynamic environment associated with adolescent obsessive-compulsive disorder.

BACKGROUND: Computational research had determined that adults with obsessive-compulsive disorder (OCD) display heightened action updating in response to noise in the environment and neglect metacognitive information (such as confidence) when making decisions. These features are proposed to underlie patients' compulsions despite the knowledge they are irrational. Nonetheless, it is unclear whether this extends to adolescents with OCD as research in this population is lacking. Thus, this study aimed to investigate the interplay between action and confidence in adolescents with OCD. METHODS: Twenty-seven adolescents with OCD and 46 controls completed a predictive-inference task, designed to probe how subjects' actions and confidence ratings fluctuate in response to unexpected outcomes. We investigated how subjects update actions in response to prediction errors (indexing mismatches between expectations and outcomes) and used parameters from a Bayesian model to predict how confidence and action evolve over time. Confidence-action association strength was assessed using a regression model. We also investigated the effects of serotonergic medication. RESULTS: Adolescents with OCD showed significantly increased learning rates, particularly following small prediction errors. Results were driven primarily by unmedicated patients. Confidence ratings appeared equivalent between groups, although model-based analysis revealed that patients' confidence was less affected by prediction errors compared to controls. Patients and controls did not differ in the extent to which they updated actions and confidence in tandem. CONCLUSIONS: Adolescents with OCD showed enhanced action adjustments, especially in the face of small prediction errors, consistent with previous research establishing 'just-right' compulsions, enhanced error-related negativity, and greater decision uncertainty in paediatric-OCD. These tendencies were ameliorated in patients receiving serotonergic medication, emphasising the importance of early intervention in preventing disorder-related cognitive deficits. Confidence ratings were equivalent between young patients and controls, mirroring findings in adult OCD research.

Impaired cognitive plasticity and goal-directed control in adolescent obsessive-compulsive disorder.

BACKGROUND: Youths with obsessive-compulsive disorder (OCD) experience severe distress and impaired functioning at school and at home. Critical cognitive domains for daily functioning and academic success are learning, memory, cognitive flexibility and goal-directed behavioural control. Performance in these important domains among teenagers with OCD was therefore investigated in this study. METHODS: A total of 36 youths with OCD and 36 healthy comparison subjects completed two memory tasks: Pattern Recognition Memory (PRM) and Paired Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED) task to quantitatively gauge learning as well as cognitive flexibility. A subset of 30 participants of each group also completed a Differential-Outcome Effect (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of goal-directed and habitual behavioural control. RESULTS: Adolescent OCD patients showed a significant learning and memory impairment. Compared with healthy comparison subjects, they made more errors on PRM and PAL and in the first stages of IED involving discrimination and reversal learning. Patients were also slower to learn about contingencies in the DOE task and were less sensitive to outcome devaluation, suggesting an impairment in goal-directed control. CONCLUSIONS: This study advances the characterization of juvenile OCD. Patients demonstrated impairments in all learning and memory tasks. We also provide the first experimental evidence of impaired goal-directed control and lack of cognitive plasticity early in the development of OCD. The extent to which the impairments in these cognitive domains impact academic performance and symptom development warrants further investigation.

The effects of oxytocin on social reward learning in humans.

It has been hypothesised that the mechanisms modulating social affiliation are regulated by reward circuitry. Oxytocin, previously shown to support affiliative behaviour and the processing of socio-emotional stimuli, is expressed in areas of the brain involved in reward and motivation. However, limited data are available that test if oxytocin is directly involved in reward learning, or whether oxytocin can modulate the effect of emotion on reward learning. In a double-blind, randomised, placebo-controlled, within-group study design, 24 typical male volunteers were administered 24 IU of oxytocin or placebo and subsequently completed an affective reward learning task. Oxytocin selectively reduced performance of learning rewards, but not losses, from happy faces. The mechanism by which oxytocin may be exerting this effect is discussed in terms of whether oxytocin is affecting identity recognition via affecting the salience of happy faces. We conclude that oxytocin detrimentally affects learning rewards from happy faces in certain contexts.

Effects of oxytocin on attention to emotional faces in healthy volunteers and highly socially anxious males.

BACKGROUND: Evidence suggests that individuals with social anxiety demonstrate vigilance to social threat, whilst the peptide hormone oxytocin is widely accepted as supporting affiliative behaviour in humans. METHODS: This study investigated whether oxytocin can affect attentional bias in social anxiety. In a double-blind, randomized, placebo-controlled, within-group study design, 26 healthy and 16 highly socially anxious (HSA) male volunteers (within the HSA group, 10 were diagnosed with generalized social anxiety disorder) were administered 24 IU of oxytocin or placebo to investigate attentional processing in social anxiety. Attentional bias was assessed using the dot-probe paradigm with angry, fearful, happy and neutral face stimuli. RESULTS: In the baseline placebo condition, the HSA group showed greater attentional bias for emotional faces than healthy individuals. Oxytocin reduced the difference between HSA and non-socially anxious individuals in attentional bias for emotional faces. Moreover, it appeared to normalize attentional bias in HSA individuals to levels seen in the healthy population in the baseline condition. The biological mechanisms by which oxytocin may be exerting these effects are discussed. CONCLUSIONS: These results, coupled with previous research, could indicate a potential therapeutic use of this hormone in treatment for social anxiety.

Trauma and mental disorder: multi-perspective depictions in Top Boy.

Psychiatry has often had an uneasy relationship with popular culture as depictions of mental health may be stigmatising and inaccurate. A recent critically acclaimed series, Top Boy, set in a crime-filled fictional housing estate in the London Borough of Hackney offers an informed and fairly balanced insight into broad mental health-related themes including racial trauma embodied in social inequities, the syndemic of mental disorder, substance misuse and gang-based crime as well as the psychosocial ramifications of illustrated mental health conditions. From both idiographic and nomothetic perspectives, Top Boy touches on a rich variety of structural determinants of mental health, as well as individual and environmental predisposition to mental disorder and substance misuse. The show offers an opportunity for education for both the broader society and the groups which suffer these syndemics. An understanding of how structural factors epidemiologically affect what psychiatric conditions individuals are likely to suffer, how they can be better reached by psychiatric services, and what interventions can help improve the socioeconomic factors that lead to the behaviours/paths that individuals end up is vital for public mental health policy.

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.

Compulsive avoidance in youths and adults with OCD: an aversive pavlovian-to-instrumental transfer study.

Compulsive behaviour may often be triggered by Pavlovian cues. Assessing how Pavlovian cues drive instrumental behaviour in obsessive-compulsive disorder (OCD) is therefore crucial to understand how compulsions develop and are maintained. An aversive Pavlovian-to-Instrumental transfer (PIT) paradigm, particularly one involving avoidance/cancellation of negative outcomes, can enable such investigation and has not previously been studied in clinical-OCD. Forty-one participants diagnosed with OCD (21 adults; 20 youths) and 44 controls (21 adults; 23 youths) completed an aversive PIT task. Participants had to prevent the delivery of unpleasant noises by moving a joystick in the correct direction. They could infer these correct responses by learning appropriate response-outcome (instrumental) and stimulus-outcome (Pavlovian) associations. We then assessed whether Pavlovian cues elicited specific instrumental avoidance responses (specific PIT) and induced general instrumental avoidance (general PIT). We investigated whether task learning and confidence indices influenced PIT strength differentially between groups. There was no overall group difference in PIT performance, although youths with OCD showed weaker specific PIT than youth controls. However, urge to avoid unpleasant noises and preference for safe over unsafe stimuli influenced specific and general PIT respectively in OCD, while PIT in controls was more influenced by confidence in instrumental and Pavlovian learning. Thus, in OCD, implicit motivational factors, but not learnt knowledge, may contribute to the successful integration of aversive Pavlovian and instrumental cues. This implies that compulsive avoidance may be driven by these automatic processes. Youths with OCD show deficits in specific PIT, suggesting cue integration impairments are only apparent in adolescence. These findings may be clinically relevant as they emphasise the importance of targeting such implicit motivational processes when treating OCD.

Excessive Checking in Obsessive-Compulsive Disorder: Neurochemical Correlates Revealed by 7T Magnetic Resonance Spectroscopy.

Background: Compulsive checking, a common symptom of obsessive-compulsive disorder (OCD), has been difficult to capture experimentally. Therefore, determination of its neural basis remains challenging despite some evidence suggesting that it is linked to dysfunction of cingulostriatal systems. This study introduces a novel experimental paradigm to measure excessive checking and its neurochemical correlates. Methods: Thirty-one patients with OCD and 29 healthy volunteers performed a decision-making task requiring them to decide whether 2 perceptually similar visual representations were the same or different under a high-uncertainty condition without feedback. Both groups underwent 7T magnetic resonance spectroscopy scans on the same day. Correlations between out-of-scanner experimental measures of checking and the glutamate/GABA (gamma-aminobutyric acid) ratio in the anterior cingulate cortex, supplementary motor area, and occipital cortex were assessed. Their relationship with subjective ratings of doubt, anxiety, and confidence was also investigated. Results: Patients with OCD exhibited excessive and dysfunctional checking, which was significantly correlated with changes in the glutamate/GABA ratio within the anterior cingulate cortex. No behavioral/neurochemical relationships were evident for either the supplementary motor area or occipital cortex. The excessive checking observed in patients was negatively correlated with their confidence levels and positively related to doubt, anxiety, and compulsivity traits. Conclusions: We conclude that experimental measures of excessive and dysfunctional checking in OCD, which have been linked to increased doubt, anxiety, and lack of confidence, are related to an imbalance between excitatory and inhibitory neural activity within the anterior cingulate cortex. This study adds to our understanding of the role of this region in OCD by providing a laboratory model of the possible development of compulsive checking.

Novel pharmacological agents targeting memory and cognition in the treatment of anxiety disorders.

OBJECTIVE: The aim of this study is to review data for several promising novel pharmacological drugs for anxiety disorders and describe how they exert their effects. METHOD: We presented a review of the published literature. Online search plus reference list checking was also used. RESULTS: The neurobiology of anxiety is overviewed. N-methyl-D-aspartate and beta adrenaline are involved in memory consolidation. We describe studies using memantine, D-cycloserine, propranolol, and riluzole that modulate these pathways. CONCLUSION: There are a number of promising new therapies, but these require further studies before they can enter routine clinical practice.

Cortical glutamate and GABA are related to compulsive behaviour in individuals with obsessive compulsive disorder and healthy controls.

There has been little analysis of neurochemical correlates of compulsive behaviour to illuminate its underlying neural mechanisms. We use 7-Tesla proton magnetic resonance spectroscopy (1H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex (ACC) and supplementary motor area (SMA) of healthy volunteers and participants with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behaviour are related to glutamate levels, whereas a behavioural index of habitual control correlates with the glutamate:GABA ratio. Participants with OCD also show the latter relationship in the ACC while exhibiting elevated glutamate and lower GABA levels in that region. This study highlights SMA mechanisms of habitual control relevant to compulsive behaviour, common to the healthy sub-clinical and OCD populations. The results also demonstrate additional involvement of anterior cingulate in the balance between goal-directed and habitual responding in OCD.

Oxytocin enhances basolateral amygdala activation and functional connectivity while processing emotional faces: preliminary findings in autistic vs non-autistic women.

Oxytocin is hypothesized to promote social interactions by enhancing the salience of social stimuli. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to face stimuli in autistic men, effects in autistic women remain unclear. In this study, the influence of intranasal oxytocin on activation and functional connectivity of the basolateral amygdala-the brain's 'salience detector'-while processing emotional faces vs shapes was tested in 16 autistic and 21 non-autistic women by functional magnetic resonance imaging in a placebo-controlled, within-subject, cross-over design. In the placebo condition, minimal activation differences were observed between autistic and non-autistic women. However, significant drug × group interactions were observed for both basolateral amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35-voxel cluster, Montreal Neurological Institute (MNI) coordinates of peak voxel = -22 -10 -28; mean change = +0.079%, t = 3.159, PTukey = 0.0166) but not among non-autistic women (mean change = +0.003%, t = 0.153, PTukey = 0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not in non-autistic women, attenuating group differences in the placebo condition. Taken together, these findings extend evidence of oxytocin's effects on the amygdala to specifically include autistic women and specify the subregion of the effect.

Association of Environmental Uncertainty With Altered Decision-making and Learning Mechanisms in Youths With Obsessive-Compulsive Disorder.

Importance: Adults with obsessive-compulsive disorder (OCD) display perseverative behavior in stable environments but exhibit vacillating choice when payoffs are uncertain. These findings may be associated with intolerance of uncertainty and compulsive behaviors; however, little is known about the mechanisms underlying learning and decision-making in youths with OCD because research into this population has been limited. Objective: To investigate cognitive mechanisms associated with decision-making in youths with OCD by using executive functioning tasks and computational modeling. Design, Setting, and Participants: In this cross-sectional study, 50 youths with OCD (patients) and 53 healthy participants (controls) completed a probabilistic reversal learning (PRL) task between January 2014 and March 2020. A separate sample of 27 patients and 46 controls completed the Wisconsin Card Sorting Task (WCST) between January 2018 and November 2020. The study took place at the University of Cambridge in the UK. Main Outcomes and Measures: Decision-making mechanisms were studied by fitting hierarchical bayesian reinforcement learning models to the 2 data sets and comparing model parameters between participant groups. Model parameters included reward and punishment learning rates (feedback sensitivity), reinforcement sensitivity and decision consistency (exploitation), and stickiness (perseveration). Associations of receipt of serotonergic medication with performance were assessed. Results: In total, 50 patients (29 female patients [58%]; median age, 16.6 years [IQR, 15.3-18.0 years]) and 53 controls (30 female participants [57%]; median age, 16.4 years [IQR, 14.8-18.0 years]) completed the PRL task. A total of 27 patients (18 female patients [67%]; median age, 16.1 years [IQR, 15.2-17.2 years]) and 46 controls (28 female participants [61%]; median age, 17.2 [IQR, 16.3-17.6 years]) completed the WCST. During the reversal phase of the PRL task, patients made fewer correct responses (mean [SD] proportion: 0.83 [0.16] for controls and 0.61 [0.31] for patients; 95% CI, -1.31 to -0.64) and switched choices more often following false-negative feedback (mean [SD] proportion: 0.09 [0.16] for controls vs 0.27 [0.34] for patients; 95% CI, 0.60-1.26) and true-positive feedback (mean [SD] proportion: 0.93 [0.17] for controls vs 0.73 [0.34] for patients; 95% CI, -2.17 to -1.31). Computational modeling revealed that patients displayed enhanced reward learning rates (mean difference [MD], 0.21; 95% highest density interval [HDI], 0.04-0.38) but decreased punishment learning rates (MD, -0.29; 95% HDI, -0.39 to -0.18), reinforcement sensitivity (MD, -4.91; 95% HDI, -9.38 to -1.12), and stickiness (MD, -0.35; 95% HDI, -0.57 to -0.11) compared with controls. There were no group differences on standard WCST measures and computational model parameters. However, patients who received serotonergic medication showed slower response times (mean [SD], 1420.49 [279.71] milliseconds for controls, 1471.42 [212.81] milliseconds for patients who were unmedicated, and 1738.25 [349.23] milliseconds for patients who were medicated) (control vs medicated MD, -320.26 [95% CI, -547.00 to -88.68]) and increased unique errors (mean [SD] proportion: 0.001 [0.004] for controls, 0.002 [0.004] for patients who were unmedicated, and 0.008 [0.01] for patients who were medicated) (control vs medicated MD, -0.007 [95% CI, -3.14 to -0.36]) on the WCST. Conclusions and Relevance: The results of this cross-sectional study indicated that youths with OCD showed atypical probabilistic reversal learning but were generally unimpaired on the deterministic WCST, although unexpected results were observed for patients receiving serotonergic medication. These findings have implications for reframing the understanding of early-onset OCD as a disorder in which decision-making is associated with uncertainty in the environment, a potential target for therapeutic treatment. These results provide continuity with findings in adults with OCD.

Action-Outcome Knowledge Dissociates From Behavior in Obsessive-Compulsive Disorder Following Contingency Degradation.

BACKGROUND: In obsessive-compulsive disorder (OCD), actions persist despite being inappropriate to the situation and without relationship to the overall goal. Dysfunctional beliefs have traditionally been postulated to underlie this condition. More recently, OCD has been characterized in terms of an imbalance between the goal-directed and the habit systems. To test these competing hypotheses, we used a novel experimental task designed to test subjective action-outcome knowledge of the effectiveness of actions (i.e., instrumental contingency), together with the balance between goal-directed and habitual responding. METHODS: Twenty-seven patients with OCD and 27 healthy control subjects were tested on a novel task involving the degradation of an action-outcome contingency. Sensitivity to instrumental contingency and the extent to which explicitly reported action-outcome knowledge guided behavior were probed by measuring response rate and subjectively reported judgments. RESULTS: Patients with OCD responded more than healthy control subjects in situations in which an action was less causally related to obtaining an outcome. However, patients showed intact explicit action-outcome knowledge, as assessed by self-report. In patients, the relationship between causality judgment and responding was altered; therefore, their actions were dissociated from explicit action-outcome knowledge. CONCLUSIONS: These findings indicate reduced sensitivity to instrumental contingency in OCD, reinforcing the notion of a deficient goal-directed system in this disorder. By showing a dissociation between subjectively reported action-outcome knowledge and behavior, the data provide experimental evidence for the ego-dystonic nature of OCD.

Confirmation of the genetic association between the U2AF homology motif (UHM) kinase 1 (UHMK1) gene and schizophrenia on chromosome 1q23.3.

UHMK1 has previously been implicated as a susceptibility gene for schizophrenia in the 1q23.3 region by significant evidence of allelic and haplotypic association between schizophrenia and several genetic markers at UHMK1 in a London-based case-control sample. Further fine mapping of the UHMK1 gene locus in the University College London schizophrenia case-control sample was carried out with tagging SNPs. Two additional SNPs were found to be associated with schizophrenia (rs6604863 P = 0.02, rs10753578 P = 0.017). Tests of allelic and haplotypic association were then carried out in a second independent sample from Aberdeen consisting of 858 individuals with schizophrenia and 591 controls. Two of these SNPs also showed association in the Aberdeen sample (rs7513662 P = 0.0087, rs10753578 P = 0.022) and several haplotypes were associated (global permutation P = 0.0004). When the UCL and Aberdeen samples were combined three SNPs (rs7513662 P = 0.0007, rs6427680 P = 0.0252, rs6694863 P = 0.015) and several haplotypes showed association (eg HAP-A, HAP-B, HAP-C permutation P = 0.00005). The finding of allelic association with markers in the UHMK1 gene might help explain why it has not been possible, despite great effort, to satisfactorily confirm previously reported associations between schizophrenia and the genes RGS4 and NOS1AP/CAPON. These genes flank UHMK1 and all three loci are within a 700 kb region showing linkage to schizophrenia. The confirmation of association between UHMK1 and schizophrenia, rather than RGS4 and NOS1AP in the London sample, points to the possibility that previous efforts to accurately fine map a gene in the 1q23.3 region have lacked accuracy or may have suffered from methodological flaws.

Reduction in occipital cortex gamma-aminobutyric acid concentrations in medication-free recovered unipolar depressed and bipolar subjects.

BACKGROUND: Studies using proton magnetic resonance spectroscopy (MRS) have indicated that unmedicated, acutely depressed patients have decreased levels of gamma-aminobutyric acid (GABA) in occipital cortex. Cortical levels of glutamate (Glu) may be increased, although these data are less consistent. The aim of this study was to use MRS to determine whether changes in GABA and Glu levels were present in patients with mood disorders who had recovered and were no longer taking medication. METHODS: An [1H]-MRS was used to measure levels of GABA, of the combined concentration of Glu and glutamine (Gln), and of N-acetylaspartate (NAA) in occipital cortex in medication-free, fully recovered subjects with a history of recurrent unipolar depression (n = 15), bipolar disorder (n = 16), and a group of healthy controls (n = 18). RESULTS: Occipital levels of GABA and NAA were significantly lower in recovered depressed and bipolar subjects than in healthy controls, whereas Glu +Gln concentrations were higher. CONCLUSIONS: Our data suggest that recovered unmedicated subjects with a history of mood disorder have changes in cortical concentrations of GABA, NAA, and Glu +Gln. These biochemical abnormalities may be markers of a trait vulnerability to mood disorder, rather than neurochemical correlates of an abnormal mood state.

Failure to confirm allelic and haplotypic association between markers at the chromosome 6p22.3 dystrobrevin-binding protein 1 (DTNBP1) locus and schizophrenia.

BACKGROUND: Previous linkage and association studies may have implicated the Dystrobrevin-binding protein 1 (DTNBP1) gene locus or a gene in linkage disequilibrium with DTNBP1 on chromosome 6p22.3 in genetic susceptibility to schizophrenia. METHODS: We used the case control design to test for of allelic and haplotypic association with schizophrenia in a sample of four hundred and fifty research subjects with schizophrenia and four hundred and fifty ancestrally matched supernormal controls. We genotyped the SNP markers previously found to be significantly associated with schizophrenia in the original study and also other markers found to be positive in subsequent studies. RESULTS: We could find no evidence of allelic, genotypic or haplotypic association with schizophrenia in our UK sample. CONCLUSION: The results suggest that the DTNBP1 gene contribution to schizophrenia must be rare or absent in our sample. The discrepant allelic association results in previous studies of association between DTNBP1 and schizophrenia could be due population admixture. However, even positive studies of European populations do not show any consistent DTNBP1 alleles or haplotypes associated with schizophrenia. Further research is needed to resolve these issues. The possible confounding of linkage with association in family samples already showing linkage at 6p22.3 might be revealed by testing genes closely linked to DTNBP1 for allelic association and by restricting family based tests of association to only one case per family.

Compulsivity Reveals a Novel Dissociation between Action and Confidence.

Confidence and actions are normally tightly interwoven-if I am sure that it is going to rain, I will take an umbrella-therefore, it is difficult to understand their interplay. Stimulated by the ego-dystonic nature of obsessive-compulsive disorder (OCD), where compulsive actions are recognized as disproportionate, we hypothesized that action and confidence might be independently updated during learning. Participants completed a predictive-inference task designed to identify how action and confidence evolve in response to surprising changes in the environment. While OCD patients (like controls) correctly updated their confidence according to changes in the environment, their actions (unlike those of controls) mostly disregarded this knowledge. Therefore, OCD patients develop an accurate, internal model of the environment but fail to use it to guide behavior. Results demonstrated a novel dissociation between confidence and action, suggesting a cognitive architecture whereby confidence estimates can accurately track the statistic of the environment independently from performance.

Specific Frontostriatal Circuits for Impaired Cognitive Flexibility and Goal-Directed Planning in Obsessive-Compulsive Disorder: Evidence From Resting-State Functional Connectivity.

BACKGROUND: A recent hypothesis has suggested that core deficits in goal-directed behavior in obsessive-compulsive disorder (OCD) are caused by impaired frontostriatal function. We tested this hypothesis in OCD patients and control subjects by relating measures of goal-directed planning and cognitive flexibility to underlying resting-state functional connectivity. METHODS: Multiecho resting-state acquisition, combined with micromovement correction by blood oxygen level-dependent sensitive independent component analysis, was used to obtain in vivo measures of functional connectivity in 44 OCD patients and 43 healthy comparison subjects. We measured cognitive flexibility (attentional set-shifting) and goal-directed performance (planning of sequential response sequences) by means of well-validated, standardized behavioral cognitive paradigms. Functional connectivity strength of striatal seed regions was related to cognitive flexibility and goal-directed performance. To gain insights into fundamental network alterations, graph theoretical models of brain networks were derived. RESULTS: Reduced functional connectivity between the caudate and the ventrolateral prefrontal cortex was selectively associated with reduced cognitive flexibility. In contrast, goal-directed performance was selectively related to reduced functional connectivity between the putamen and the dorsolateral prefrontal cortex in OCD patients, as well as to symptom severity. Whole-brain data-driven graph theoretical analysis disclosed that striatal regions constitute a cohesive module of the community structure of the functional connectome in OCD patients as nodes within the basal ganglia and cerebellum were more strongly connected to one another than in healthy control subjects. CONCLUSIONS: These data extend major neuropsychological models of OCD by providing a direct link between intrinsically abnormal functional connectivity within dissociable frontostriatal circuits and those cognitive processes underlying OCD symptoms.