Obsessive-compulsive disorder is characterized by decreased Pavlovian influence on instrumental behavior.

Obsessive-compulsive disorder (OCD) is characterized by uncontrollable repetitive actions thought to rely on abnormalities within fundamental instrumental learning systems. We investigated cognitive and computational mechanisms underlying Pavlovian biases on instrumental behavior in both clinical OCD patients and healthy controls using a Pavlovian-Instrumental Transfer (PIT) task. PIT is typically evidenced by increased responding in the presence of a positive (previously rewarded) Pavlovian cue, and reduced responding in the presence of a negative cue. Thirty OCD patients and thirty-one healthy controls completed the Pavlovian Instrumental Transfer test, which included instrumental training, Pavlovian training for positive, negative and neutral cues, and a PIT phase in which participants performed the instrumental task in the presence of the Pavlovian cues. Modified Rescorla-Wagner models were fitted to trial-by-trial data of participants to estimate underlying computational mechanism and quantify individual differences during training and transfer stages. Bayesian hierarchical methods were used to estimate free parameters and compare the models. Behavioral and computational results indicated a weaker Pavlovian influence on instrumental behavior in OCD patients than in HC, especially for negative Pavlovian cues. Our results contrast with the increased PIT effects reported for another set of disorders characterized by compulsivity, substance use disorders, in which PIT is enhanced. A possible reason for the reduced PIT in OCD may be impairment in using the contextual information provided by the cues to appropriately adjust behavior, especially when inhibiting responding when a negative cue is present. This study provides deeper insight into our understanding of deficits in OCD from the perspective of Pavlovian influences on instrumental behavior and may have implications for OCD treatment modalities focused on reducing compulsive behaviors.

Imbalance between the caudate and putamen connectivity in obsessive-compulsive disorder.

BACKGROUND: Compulsive behaviors in obsessive-compulsive disorder (OCD) have been suggested to result from an imbalance in cortico-striatal connectivity. However, the nature of this impairment, the relative involvement of different striatal areas, their imbalance in genetically related but unimpaired individuals, and their relationship with cognitive dysfunction in OCD patients, remain unknown. METHODS: In the current study, striatal (i.e., caudate and putamen) whole-brain connectivity was computed in a sample of OCD patients (OCD, n = 62), unaffected first-degree relatives (UFDR, n = 53) and healthy controls (HC, n = 73) by ROI-based resting-state functional magnetic resonance imaging (rs-fMRI). A behavioral task switch paradigm outside of the scanner was also performed to measure cognitive flexibility in OCD patients. RESULTS: There were significantly increased strengths (Z-transformed Pearson correlation coefficient) in caudate connectivity in OCD patients. A significant correlation between the two types of connectivity strengths in the relevant regions was observed only in the OCD patient group. Furthermore, the caudate connectivity of patients was negatively associated with their task-switch performance. CONCLUSIONS: The imbalance between the caudate and putamen connectivity, arising from the abnormal increase of caudate activity, may serve as a clinical characteristic for obsessive-compulsive disorder.

Dysfunction of goal-directed control in patients with depression and nonsuicidal self-injury.

BACKGROUND: Non-suicidal self-injury (NSSI) is a common problem associated with dangerous outcomes. Dysfunction of goal-directed behavioral control may contribute to NSSI. To test this, we used a novel experimental paradigm (Pavlovian-to-Instrumental Transfer, PIT) to test whether patients with NSSI utilize Pavlovian conditioned stimuli (CSs) during goal-directed control of ongoing behavior. METHODS: Thirty-five depressed patients with NSSI (D-NSSI) and thirty-four healthy controls performed a PIT task. We measured the influence of positive and negative background CSs on instrumental responses for rewards. RESULTS: The results showed that D-NSSI performed significantly lower PIT than controls, and PIT measures were negatively correlated with NSSI frequency. Furthermore, in a subset of patients exhibiting high levels of compulsivity, PIT positively moderated the relationship between compulsivity and NSSI frequency. CONCLUSIONS: These results indicate that D-NSSI patients have difficulties in using different CSs to control ongoing behavior in a goal-directed manner, and the dysfunction of goal-directed control may contribute to NSSI.

White Matter Alterations of the Goal-Directed System in Patients With Obsessive-Compulsive Disorder and Their Unaffected First-Degree Relatives.

BACKGROUND: It has been postulated that the neurobiological mechanism responsible for the onset of symptoms of obsessive-compulsive disorder (OCD), especially compulsive behavior, is related to alterations of the goal-directed and habitual learning systems. However, little is known about whether changes in these learning systems co-occur with changes in the white matter structure of patients with OCD and their unaffected first-degree relatives (UFDRs). METHODS: Diffusion tensor imaging data were acquired from 32 patients with OCD (21 male), 32 UFDRs (16 male), and 32 healthy control subjects (16 male). White matter tracts in the goal-directed and habitual networks were reconstructed with seed-based probabilistic tractography. Partial least squares path modeling was used to measure the covariation between white matter connectivity, psychiatric symptoms, and cognitive flexibility. RESULTS: Patients with OCD showed reduced connectivity in the fiber tracts within the goal-directed but not within the habitual network compared with healthy control subjects. Using partial least squares path modeling, patients' symptoms were negatively associated with connectivity within the goal-directed but not within the habitual network. Cognitive flexibility was correlated negatively with caudate-dorsolateral prefrontal cortex tracts in patients with OCD. UFDRs also exhibited reduced white matter connectivity in the goal-directed network. CONCLUSIONS: These findings suggest that the balance of learning systems in OCD may be disrupted, mainly impairing white matter in the goal-directed network. Alterations of the goal-directed network could explain overt symptoms and impaired cognitive flexibility in patients with OCD. Similar alterations in the goal-directed network are present in UFDRs. The impaired goal-directed system may be an endophenotype of OCD.

Abnormal Anhedonia as a Potential Endophenotype in Obsessive-Compulsive Disorder.

BACKGROUND: Obsessive-compulsive disorder (OCD) is often accompanied by cognitive, particularly executive function, impairments. Recently, anhedonia has emerged as an apparently important symptom of OCD reflecting altered emotion regulation. These two aspects are often comorbid in OCD. However, little is known about whether anhedonia may be a trait marker for OCD. METHODS: To verify the role of executive function and evaluate the role of anhedonia in OCD and its relationship with OCD symptoms, we recruited 60 OCD patients, 30 unaffected first-degree relatives (FDRs), and 60 healthy controls (HCs). Participants completed psychometric testing to assess depression, anxiety, and anhedonia symptoms, as well as two cognitive tests to assess executive function, namely the Wisconsin Card Sorting Test (WCST) and the Stroop Color-Word Test (SCWT). RESULTS: Compared to HCs, OCD patients and FDRs had significantly lower anticipatory and consummatory pleasure scores. The severity of anticipatory anhedonia correlated positively with obsessive-compulsive symptoms (r = 0.253, p = 0.009), even after controlling for depression and anxiety symptoms. Compared to HCs, OCD patients and FDRs made more errors and achieved fewer categories in the WCST. For all three SWCT components, OCD patients and FDRs took more time to name colors than HCs, but the three groups had similar numbers of errors. CONCLUSION: This family-based study showed dampened pleasure together with cognitive dysfunction in OCD patients. The similar consummatory pleasure findings between OCD and FDR groups suggest anhedonia may be considered as a candidate OCD endophenotype.