Intolerance of uncertainty (IU) is a transdiagnosed vulnerability for many mental disorders. Habit is a potential cognitive construct that links to intolerance of uncertainty and symptom dimensions. This study adopted a transdiagnose perspective to investigate the mediation effect of habit features between symptom dimensions and intolerance of uncertainty in a Chinese community sample.

We recruited 4102 Chinese adults age ranged from 18 to 67 (M = 26.9, SD = 8.01) to extract psychopathological symptom dimensions and explore the mediation roles of habit features.

The study extracted three symptom dimensions (compulsivity, addiction and affective stress dimension). All symptom dimensions, IU and habit features were significantly related (p < 0.01). IU had a direct positive influence on all three dimensions (compulsivity: effect = 0.41; affective stress: effect = 0.58; addiction: effect = 0.13), it lso have an indirect positive impact via habit feature of automaticity (compulsivity: effect = 0.095; affective stress: effect = 0.062; addiction: effect = 0.050). Additionally, IU can positively influence compulsivity dimension (effect = 0.053) and negatively affective stress (effect = -0.026) dimension through routine feature of habit.

Higher level of IU can intensify symptom dimension by habit feature of automaticity, while habit feature of routine can alleviate affective stress dimension and aggravate compulsivity dimension.

Work addiction (WA) is characterized by excessive and compulsive working patterns that detrimentally affect the individual's health and functioning. While prior studies have indicated an overreliance on habit learning in various addictions, this study is the first to examine its role in WA. 104 adults were categorized into low-risk and high-risk groups for WA based on their scores on the Work Addiction Risk Test. We used a probabilistic sequence learning task designed to assess habit learning through the implicit acquisition of structured patterns characterized by alternating sequences. No significant differences were observed between the groups, both in terms of accuracy and reaction time. These findings suggest that individuals with WA exhibit intact habit learning, indicating that the addictive nature of work behavior may not solely stem from habitual processes. This highlights the unique features of WA compared to other addictions, potentially contributing to the relatively better overall functioning observed in affected individuals.

Obsessive-Compulsive Disorder (OCD) may involve an imbalance between goal-directed and habitual learning systems, and this study investigates the structural and functional brain networks underpinning these systems in OCD. Using predefined brain regions, structural and functional connectivity networks were constructed, and methods such as network-based statistics, average connectivity strength, structural-functional coupling, and partial least squares path modeling were employed to compare OCD patients and healthy controls. The results revealed that OCD patients showed increased structural connectivity within both the goal-directed and habitual learning networks, particularly in the subnetwork that connects these systems. However, functional connectivity strength was reduced in both the habitual learning network and the subnetwork connecting goal-directed and habitual learning systems. The symptoms of ordering and hoarding are, to some extent, correlated with the structural-functional coupling network and network characteristics. These findings suggest that alterations in both structural and functional brain networks underpin goal-directed and habitual learning in OCD, with increased structural connectivity potentially reflecting compensatory mechanisms, while reduced functional connectivity may contribute to the symptoms of OCD. Further research is required to better understand the complex interplay between these learning systems in OCD, considering symptom heterogeneity and disease's progression.

Habits are automatic behaviors triggered by specific cues and are thought to optimize daily activities by reducing cognitive effort and enabling efficient and fast performance. Yet, they can also lead to inflexibility, preventing individuals from adapting to environmental changes. Since it has been difficult to examine habit formation in humans with traditional outcome devaluation paradigms, we applied a motor sequence learning task (MSLT) to study this process. Thirty-one participants (16 female, 28.4 ± 5.3 years old) completed the MSLT on two consecutive days. They implicitly learned to execute a 12-item motor sequence using four fingers, each corresponding to one of four distinct visual stimulus locations. Test blocks introduced sequence deviations by intermittently omitting one item of the sequence. We measured whether participants were able to flexibly adapt their behavior or would incorrectly execute the omitted response - a so-called action slip. Action slips serve as an indicator of automatization or behavioral inflexibility. Findings indicate that prolonged training led to faster response times and lower error rates in learning compared to random blocks, suggesting successful sequence learning and the emergence of automatic behaviors. Action slips increased with extensive training, demonstrating the shift towards automatic and inflexible responding, indicative of habit formation. The results highlight the utility of the MSLT in studying habit formation in humans and emphasize the role of extensive training, motor skills, and automaticity. The task offers a promising framework for investigating the neural and cognitive mechanisms underlying habitual behavior, providing new insights into the balance between habitual and goal-directed control.

Growing evidence has identified potential biomarkers of cognitive-behavioural therapy (CBT) efficacy in obsessive-compulsive disorder (OCD). Genetic and epigenetic mechanisms (e.g., polymorphisms, DNA methylation) contribute to OCD pathogenesis and CBT response variability, establishing them as a key research focus. To evaluate their associations with CBT outcomes in OCD, we conducted a systematic review of PubMed, Web of Science, CNKI, and Cochrane Library (from inception to January 2025), identifying eight studies that met rigorous inclusion criteria. The identified predictors included: (1) Genetic polymorphisms (BDNF); (2) Epigenetic modifications (DNA methylation of MAOA, SLC6A4, OXTR, PIWIL1, MIR886, PLEKHA1, KCNQ1, TRPM8, HEBP1, HTR7P1, MAPK8IP3, ENAH, RABGGTB (SNORD45C), MYEF2, GALK2, CEP192, and UIMC1). These markers may influence neural plasticity, neurotransmitter regulation, and related processes, providing molecular substrates for the observed treatment effects. Converging evidence suggests that distinct neurocognitive mechanisms may mediate CBT efficacy in OCD, particularly fear extinction learning and goal-directed behaviors (GDBs), which we analyze mechanistically. Future studies should integrate polygenic risk scores (PRS) with functional neuroimaging to dissect individual variability in CBT response, mainly through cortico-striato-thalamo-cortical (CSTC) circuit profiling. To our knowledge, this is the first systematic review synthesizing genetic and epigenetic predictors of CBT response in OCD; these findings provide compelling evidence for biomarkers for CBT personalization in OCD, advancing a novel precision psychiatry framework.

Obsessive-compulsive disorder (OCD) has long been conceptualized as a neuron-centric disorder of cortico-striato-thalamo-cortical (CSTC) circuit dysregulation. However, a growing body of evidence is now reframing this narrative, placing astrocytes-once relegated to passive support roles-at the center of OCD pathophysiology. Astrocytes are critical regulators of glutamate and GABA homeostasis, calcium signaling, and synaptic plasticity, all of which are disrupted in OCD. Recent high-resolution molecular and proteomic studies reveal that specific astrocyte subpopulations, including Crym-positive astrocytes, directly shape excitatory/inhibitory balance and control perseverative behaviors by modulating presynaptic inputs from the orbitofrontal cortex. Disruptions in astrocytic neurotransmitter clearance and dopamine metabolism amplify CSTC circuit hyperactivity and reinforce compulsions. This review reframes OCD as a disorder of neuro-glial dysfunctions, proposing that targeting astrocytic signaling, metabolism, and structural plasticity may unlock transformative therapeutic strategies. By integrating human and animal data, we advocate for a glial-centric model of OCD that not only enhances mechanistic understanding but also opens new frontiers for precision treatment.

Impaired cognitive flexibility is associated with the characteristic symptomatology of ADHD and OCD. However, the mechanisms underlying learning and flexibility under uncertainty in adults with OCD or ADHD remain unclear. This study aimed to identify the mechanisms underlying contingency-based flexibility in a sample of adults with ADHD or OCD, using probabilistic learning reversal task, functional near-infrared spectroscopy, and computational modelling.

148 Spanish-speaking adults (43 OCD, 53 ADHD and 52 healthy controls) completed a probabilistic learning reversal task. Previously, we obtained a resting-state functional connectivity (rsFC) record between several frontoparietal network regions using functional near-infrared spectroscopy. Contingency-based flexibility was explored by reinforcement learning model in combination with a Bayesian Generalized Logistic Model (GLM). The reinforcement learning parameters included reward and punishment learning rates (feedback sensitivity), and inverse temperature (decision consistency). Bayesian GLM parameters were defined to measure final accuracy, learning and speed of learning.

We found that the groups showed optimal performance in the discrimination block and a higher performance of healthy controls compared to patients in the reversal block. Model parameters predicted task performance differently by phase and group. In the discrimination block, while the performance of healthy controls was predicted by a combination of parameters such as high inverse temperature and punishment learning rate together with low values of reward learning rate, in the case of the clinical groups it was only by high inverse temperature. In the reversal block, the performance of OCD was predicted by high punishment learning rate and that of ADHD by low reward learning rate; in contrast, the performance of healthy controls was also predicted by a combination of parameters with high punishment learning rate and inverse temperature as predictors. We found the rsFC between the left and right posterior parietal cortex appears to credibly predict performance in the discrimination block in healthy controls.

These results suggest that OCD and ADHD in adults could be associated with poor behavioral adaptation when reinforcement-punishment contingencies changed. The difficulties observed in ADHD and OCD likely stem from different underlying mechanisms that affect both learning and switching processes. Findings highlighted how OCD appears to show greater sensitivity to punishment when there is uncertainty about the behavior-outcome association. Instead, the ADHD group can be guided by sensitivity to reinforcement. Interhemispheric rsFC posterior parietal cortex could be important for optimal learning of the task.

Obsessive-compulsive disorder (OCD) and eating disorders (EDs) are highly comorbid. Despite the high comorbidity, there is little understanding of why these disorders coexist and even less research on how to best treat this co-occurrence. In this article, we review the literature on comorbid OCD-ED and discuss potential underlying shared mechanisms, including anxiety/avoidance, perfectionism, intolerance of uncertainty, habit formation, disgust, shame and guilt, rumination, metacognitive beliefs, and shared biological characteristics. We then discuss prior models of OCD-ED comorbidity and shift the perspective from latent or categorical models to dimensional symptom models (e.g., network models). We describe how dimensional symptom models could advance the conceptualization, treatment, and prevention of comorbid OCD-ED. Next, we discuss how idiographic (one-person) symptom models could advance personalized treatment and provide a treatment example. Finally, we discuss future research needed to advance the field and improve treatment outcomes.

Obsessive-compulsive (OC) tendencies involve intrusive thoughts and rigid, repetitive behaviours that also manifest at the subclinical level in the general population. The neurocognitive factors driving the development and persistence of the excessive presence of these tendencies remain highly elusive, though emerging theories emphasize the role of implicit information processing. Despite various empirical studies on distinct neurocognitive processes, the incidental retrieval of environmental structures in dynamic and noisy environments, such as probabilistic learning, has received relatively little attention.

In this study, we aimed to unravel potential individual differences in implicit probabilistic learning and the updating of predictive representations related to OC tendencies in a non-clinical population. We conducted two independent online experiments (NStudy1 = 164, NStudy2 = 256) with university students. Probabilistic learning was assessed using an implicit visuomotor probabilistic learning task, involving sequences with second-order non-adjacent dependencies.

Our findings revealed that implicit probabilistic learning remained remarkably robust among OC tendencies within a non-clinical population. Furthermore, the results highlighted effective updating capabilities of predictive representations, which were not influenced by OC tendencies.

These results offer new insights into individual differences in probabilistic learning and updating in relation to OC tendencies, contributing to theoretical, methodological, and practical approaches for understanding the maladaptive behavioural manifestations of OC disorder and subclinical tendencies.

Dopamine modulates corticostriatal plasticity in both the direct and indirect pathways of the cortico-striato-thalamo-cortical (CSTC) loops. These gradual changes in corticostriatal synaptic strengths produce long-lasting changes in behavioral responses. Under normal conditions, these mechanisms enable the selection of the most appropriate responses while inhibiting others. However, under dysregulated dopamine conditions, including a lack of dopamine release or dopamine signaling, these mechanisms could lead to the selection of maladaptive responses and/or the inhibition of appropriate responses in an experience-dependent and task-specific manner. In this review, we propose that preventing or reversing such maladaptive synaptic strengths and erasing such aberrant "memories" could be a disease-modifying therapeutic strategy for many neurological and psychiatric disorders. We review evidence from Parkinson's disease, drug-induced parkinsonism, L-DOPA-induced dyskinesia, obsessive-compulsive disorder, substance use disorders, and depression as well as research findings on animal disease models. Altogether, these studies allude to an emerging theme in translational neuroscience and promising new directions for therapy development. Specifically, we propose that combining pharmacotherapy with behavioral therapy or with deep brain stimulation (DBS) could potentially cause desired changes in specific neural circuits. If successful, one important advantage of correcting aberrant synaptic plasticity is long-lasting therapeutic effects even after treatment has ended. We will also discuss the potential molecular targets for these therapeutic approaches, including the cAMP pathway, proteins involved in synaptic plasticity as well as pathways involved in new protein synthesis. We place special emphasis on RNA binding proteins and epitranscriptomic mechanisms, as they represent a new frontier with the distinct advantage of rapidly and simultaneously altering the synthesis of many proteins locally.

Habits are important in everyday life and are thought to be involved in several human behavioral pathologies, including addictions. Experiments with rats suggest that habit, as indexed by insensitivity of an instrumental response to separate devaluation of its outcome, develops with extended practice. Motivated behavior often involves a sequence or chain of behaviors (Rs), with each cued by a different discriminative stimulus (S). We therefore examined performance of a two-response discriminated heterogeneous behavior chain (R1-R2) in which R1 and R2 were occasioned by different Ss and were both required to earn a reinforcer. We further asked whether extended training decreases the sensitivity of R1 to the extinction of R2, which is known to decrease R1 and is analogous to an outcome devaluation effect. In Experiment 1 with rats, R1 was sensitive to extinction of R2 after moderate but not extended training, suggesting the development of habit. In Experiment 2, human participants learned three R1-R2 chains before one "R2" was extinguished. Extinction of R2 specifically decreased performance of the R1 that had been associated with it, but extended training did not reduce this effect. Based on findings in the nonhuman literature, Experiment 3 then had human participants learn only one R1-R2 chain before R2 was extinguished. Under these conditions, R1 became insensitive to extinction of R2 after extended training, consistent with the idea that habit can develop in a laboratory experiment with humans. The findings are discussed relative to difficulties demonstrating habits in humans. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Chronic stress can change how we learn and, thus, how we make decisions1-5. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted systems neuroscience approach in male and female mice, we reveal a dual-pathway, amygdala-striatal neuronal circuit architecture by which a recent history of chronic stress disrupts the action-outcome learning underlying adaptive agency and promotes the formation of inflexible habits. We found that the projection from the basolateral amygdala to the dorsomedial striatum is activated by rewarding events to support the action-outcome learning needed for flexible, goal-directed decision-making. Chronic stress attenuates this to disrupt action-outcome learning and, therefore, agency. Conversely, the projection from the central amygdala to the dorsomedial striatum mediates habit formation. Following stress, this pathway is progressively recruited to learning to promote the premature formation of inflexible habits. Thus, stress exerts opposing effects on two amygdala-striatal pathways to disrupt agency and promote habit. These data provide neuronal circuit insights into how chronic stress shapes learning and decision-making, and help understanding of how stress can lead to the disrupted decision-making and pathological habits that characterize substance use disorders and mental health conditions.

The mechanisms that underlie obsessive-compulsive disorder (OCD) are elusive. The habit formation model of OCD postulates that compulsions arise from an imbalance between goal-directed and habit formation systems, stemming from impaired inhibition of stimulus-driven actions. Few studies have examined the core tenets of the habit formation model in pediatric OCD. We administered the object-interference task, which assesses the ability to inhibit stimulus-driven behavior, to 67 youths with OCD, 43 youths with an anxiety disorder (and no OCD), and 48 youths without any mental disorder. Impaired inhibition of stimulus-driven behavior was calculated by comparing response times to neutral non-nameable objects, neutral nameable objects, distress-eliciting objects, and incompleteness-eliciting objects. Youths with OCD did not differ significantly from youths with anxiety disorders and the non-clinical group on any response cost measure. All groups showed small response costs in relation to all three categories of non-neutral objects, with the clearest cost emerging in relation to distress-eliciting objects. Individual differences in response cost were not significantly correlated with any interview- or self-rated measure of OCD severity. Using the object-interference task, no evidence was found for impaired inhibition of stimulus-driven behavior in youths with OCD. We explore several possible interpretations of this result, including limitations of the task itself, the broader constraints of experimental methods in detecting such mechanisms, and the possibility that an imbalance between goal-directed and habit systems may not be a fundamental feature of pediatric OCD.

Obsessive-compulsive disorder (OCD) is a clinically heterogeneous disorder. The results of symptom-based classification studies are inconsistent in resolving this heterogeneity. The aim of this study was to investigate clinical differences between clusters created according to neurocognitive performance.

This study combined data sets from three previously published studies. A total of 135 outpatients diagnosed with OCD, and 106 healthy controls (HCs) were evaluated using the 17-Item Hamilton Depression Rating Scale (HDRS-17) and a comprehensive neuropsychological battery. Patients were also administered the Yale-Brown Obsessive Compulsive Scale (Y-BOCS).

Two neurocognitive subgroups were identified by k-means cluster analysis: globally impaired (GI, n = 42) and cognitively intact (CI, n = 93). The GI subgroup performed worse than the HC and CI groups on all neurocognitive tests. There was no difference between the CI group and HC in any cognitive domains. Compulsive symptom severity [t(133) = -2.45, p = 0.015], Y-BOCS total score [t(133) = -2.09, p = 0.038], and age of onset were higher in the GI group than in the CI group [t(132) = -4.24, p < 0.001]. Years of education were higher in the CI and HC groups than in the GI group [F(238) = 35.27, p < 0.001]. There was no difference in symptom profile between the CI and GI groups.

The identified cognitive clusters may indicate subtypes with different neurobiological bases. A better dissection of the cognitive structure of OCD could potentially facilitate genetic and neuroimaging studies.

Processes formalized in classic Reinforcement Learning (RL) theory, such as model-based (MB) control, habit formation, and exploration have proven fertile in cognitive and computational neuroscience, as well as computational psychiatry. Dysregulations in MB control and exploration and their neurocomputational underpinnings play a key role across several psychiatric disorders. Yet, computational accounts mostly study these processes in isolation. The current study extended standard hybrid models of a widely-used sequential RL-task (two-step task; TST) employed to measure MB control. We implemented and compared different computational model extensions for this task to quantify potential exploration and perseveration mechanisms. In two independent data sets spanning two different variants of the task, an extended hybrid RL model with a higher-order perseveration and heuristic-based exploration mechanism provided the best fit. While a simpler model with complex perseveration only, was equally well equipped to describe the data, we found a robust positive effect of directed exploration on choice probabilities in stage one of the task. Posterior predictive checks further showed that the extended model reproduced choice patterns present in both data sets. Results are discussed with respect to implications for computational psychiatry and the search for neurocognitive endophenotypes.

Extracting spatial or temporal patterns across experiences is essential for skill acquisition and predictive processes. The prefrontal cortex plays a central role in regulating competitive cognitive systems, with a particular influence on executive functions, often opposing statistical learning. This regulatory function may account for observed improvements in the acquisition and consolidation of statistical regularities following inhibition of the dorsolateral prefrontal cortex via repetitive transcranial magnetic stimulation. However, whether access to previously acquired statistical knowledge can similarly benefit from dorsolateral prefrontal cortex inhibition remains unclear. This preregistered study investigated the dorsolateral prefrontal cortex's role in retrieving pre-existing statistical knowledge of temporal regularities. Healthy human participants engaged in an implicit probabilistic sequence learning task followed by a 24-h consolidation period. Before retesting, they received either 1 Hz repetitive transcranial magnetic stimulation or sham stimulation over the left, right, or bilateral dorsolateral prefrontal cortex for 10 min. We observed that retrieval of statistical regularities was enhanced in the Bilateral dorsolateral prefrontal cortex group compared to the Sham group. Our findings suggest that dorsolateral prefrontal cortex inhibition may facilitate access to statistical knowledge, particularly when interhemispheric compensatory mechanisms are limited. These insights advance our understanding of the dynamic neural background of statistical learning and may inform strategies for cognitive enhancement.

Adaptive decision making requires agency, knowledge that actions produce particular outcomes. For well-practiced routines, agency is relinquished in favor of habit. Here, we asked how dorsomedial striatum D1+ and D2/A2A+ neurons contribute to agency and habit. We imaged calcium activity of these neurons as mice learned to lever press with agency and formed habits with overtraining. Whereas many D1+ neurons stably encoded actions throughout learning and developed encoding of reward outcomes, A2A+ neurons reorganized their encoding of actions from initial action-outcome learning to habit formation. Chemogenetic manipulations indicated that both D1+ and A2A+ neurons support action-outcome learning, but only D1+ neurons enable the use of such agency for adaptive, goal-directed decision making. These data reveal coordinated dorsomedial striatum D1+ and A2A+ function for the development of agency, cell-type specific stability and reorganization underlying agency and habit, and important insights into the neuronal circuits of how we learn and decide.

Habits are an essential part of everyday decision-making. However, the mechanisms underlying habit formation and expression in humans are difficult to study in the laboratory, owing to a dearth of convenient experimental paradigms that reliably exhibit a key marker of habits - training-induced inflexibility - under ecologically valid conditions. This difficulty is often attributed to the fact that habits are identified in contrast to goal-directed (GD) control, which research participants typically engage strongly in laboratory experiments. To address this gap, we develop a new, short habit learning paradigm that incorporates several features we hypothesized would encourage participants to disengage GD control, enabling habits to exert greater influence over behavior: a hierarchical multi-step trial structure, opportunities for self-correction, and frequent switches between extensively and moderately practiced behaviors. Through a series of experiments, we demonstrate that overtraining amplifies habitual control, as evidenced by errors biased toward the overtrained context and away from the moderately-trained context at early response times, while later responses remain dominated by GD control. The reliability of this overtraining effect depended on the inclusion of task features designed to dampen GD control. In addition to providing a practical, robust, and flexible tool for studying the cognitive processes underlying habit formation and habitual control, our paradigm moves us beyond the traditional stimulus-response conception of habits, expanding the definition to include more complex, hierarchical behaviors that better reflect naturalistic human habits.

Developmental trajectories during the transition from adolescence to adulthood contribute to the establishment of stable, adult forms of operation. Understanding the neural mechanisms underlying this transition is crucial for identifying variability in normal development and the onset of psychiatric disorders, which typically emerge during this time. Habitual behaviors can serve as a model for understanding brain mechanisms underlying the stabilization of adult behavior, while also conferring risk for psychopathologies. Dopaminergic (DA) processes in the basal ganglia are thought to facilitate the formation of habits; however, developmental trajectories of habits and the brain systems supporting them have not been characterized in vivo in developing humans. The current study examined trajectories of habitual behavior from adolescence to adulthood and sought to understand how the maturing striatal DA system may act as a potential mechanism in the process of habit formation. We used data from two longitudinal studies (combined n = 217, 10 - 32 years of age, 1-3 visits each, 320 total sessions) to characterize normative developmental trajectories of basal ganglia tissue iron concentration (a proxy for DA-related neurophysiology) and goal-direct and habitual control behaviors in a two-stage decision-making task. Tissue iron concentrations across the basal ganglia and habitual responding during the two-stage sequential decision-making task both increased with age (all p < 0.001). Importantly, habitual responding was associated with tissue iron concentrations in the putamen (F = 4.34, p = 0.014), such that increases in habitual responding were supported by increases in putamen tissue iron concentration during childhood through late adolescence. Exploratory analyses of further subdivisions of anatomical regions found that this association was specific to the posterior putamen. These results provide novel evidence in humans that habitual behavior continues to mature into adulthood and may be supported by increased specialization of reward systems.

Deer mice (Peromyscus maniculatus bairdii), a wildtype species native to North America, have been investigated for their spontaneous compulsive-like behaviour. The repetitive and persistence nature of three unique compulsive-like phenotypes in deer mice, i.e., high stereotypy (HS), large nesting behaviour (LNB) and high marble burying (HMB), are characterized by behavioural and cognitive rigidity. In this narrative review, we summarize key advances in the model's application to study obsessive-compulsive disorder (OCD), emphasizing how it may be used to investigate neurobiological and neurocognitive aspects of rigidity. Indeed, deer mice provide the field with a unique naturalistic and spontaneous model system of behavioural and cognitive rigidity that is useful for investigating the psychobiological mechanisms that underpin a range of compulsive-like phenotypes. Throughout the review, we highlight new opportunities for future research.

Habits are the behavioral output of two brain systems. A stimulus-response (S-R) system that encourages us to efficiently repeat well-practiced actions in familiar settings, and a goal-directed system concerned with flexibility, prospection, and planning. Getting the balance between these systems right is crucial: an imbalance may leave people vulnerable to action slips, impulsive behaviors, and even compulsive behaviors. In this review we examine how recent advances in our understanding of these competing brain mechanisms can be harnessed to increase the control over both making and breaking habits. We discuss applications in everyday life, as well as validated and emergent interventions for clinical populations affected by the balance between these systems. As research in this area accelerates, we anticipate a rapid influx of new insights into intentional behavioral change and clinical interventions, including new opportunities for personalization of these interventions based on the neurobiology, environmental context, and personal preferences of an individual.

Functions associated with processing reward-related information are fundamental drivers of motivation, learning, and goal-directed behavior. Such functions have been classified as the positive valence system under the Research Domain and Criteria (RDoC) criteria and are negatively impacted across a range of psychiatric disorders and mental illnesses. The positive valence system is composed of three comprehensive categories containing related but dissociable functions that are organized into either Reward Responsiveness, Reward Learning, or Reward Valuation. The presence of overlapping behavioral dysfunction across diagnostic mental disorders is in-part what motivated the RDoC initiative, which emphasized that the study of mental illness focus on investigating relevant behavior and cognitive functions and their underlying mechanisms, rather than separating efforts on diagnostic categories (i.e., transdiagnostic). Moreover, the RDoC approach is well-suited for preclinical neuroscience research, as the rise in genetic toolboxes and associated neurotechnologies enables researchers to probe specific cellular targets with high specificity. Thus, there is an opportunity to dissect whether behaviors and cognitive functions are supported by shared or distinct neural mechanisms. For preclinical research to effectively inform our understandings of human behavior however, the cognitive and behavioral paradigms should have predictive, neurobiological, and pharmacological predictive validity to the human test. Touchscreen-based testing systems provide a further advantage for this endeavor enabling tasks to be presented to animals using the same media and task design as in humans. Here, we outline the primary categories of the positive valence system and review the work that has been done cross-species to investigate the neurobiology and neurochemistry underlying reward-related functioning. Additionally, we provide clinical tasks outlined by RDoC, along with validity and/or need for further validation for analogous rodent paradigms with a focus on implementing the touchscreen-based cognitive testing systems.

The high heterogeneity observed among patients with obsessive-compulsive disorder (OCD) underscores the need to identify neurophysiological OCD subtypes to facilitate personalized diagnosis and treatment. In this study, our aim was to identify potential OCD subtypes based on individualized functional connectome abnormalities. We recruited a total of 99 patients with OCD and 104 healthy controls (HCs) matched for demographic characteristics. Individualized functional connectome abnormalities were obtained using normative models of functional connectivity strength (FCS) and used as features to unveil OCD subtypes. Sensitivity analyses were conducted to assess the reproducibility and robustness of the clustering outcomes. Patients exhibited significant intersubject heterogeneity in individualized functional connectome abnormalities. Two subtypes with distinct patterns of FCS abnormalities relative to HCs were identified. Subtype 1 patients primarily exhibited significantly decreased FCS in regions including the frontal gyrus, insula, hippocampus, and precentral/postcentral gyrus, whereas subtype 2 patients demonstrated increased FCS in widespread brain regions. When all patients were combined, no significant differences were observed. Additionally, the identified subtypes showed significant differences in age of onset. Furthermore, sensitivity analyses confirmed the reproducibility of our subtyping results. In conclusion, the identified OCD subtypes shed new light on the taxonomy and neurophysiological heterogeneity of OCD.

Exposure with Response Prevention (ERP) is a first-line treatment for OCD, but even when combined with first-line medications it is insufficiently effective for approximately half of patients. Compulsivity in OCD is thought to arise from an imbalance of two distinct neural circuits associated with specific subregions of striatum. Targeted modulation of these circuits via key cortical nodes (dorsolateral prefrontal cortex [dlPFC] or presupplementary motor area [pSMA]) has the potential to improve ERP efficacy by decreasing compulsions during therapy.

The NExT (Neuromodulation + Exposure Therapy) trial is a two-phase, multisite early-stage randomized controlled trial designed to examine whether TMS augmentation of ERP alters activity in dlPFC and/or pSMA-associated circuitry and reduces compulsions during therapy in youth with OCD age 12-21 years. Phase 1 (N = 60) will compare two different active TMS regimens with sham: A. continuous theta burst stimulation (cTBS) to pSMA vs. B. intermittent theta burst stimulation (iTBS) to dlPFC. A priori "Go/No-Go" criteria will inform a decision to proceed to Phase 2 and the choice of TMS regimen. Phase 2 (N = 60) will compare the selected TMS regimen vs. sham in a new sample.

This trial is the first to test TMS augmentation of ERP in youth with OCD. Results will inform the potential of TMS to enhance ERP efficacy and enhance knowledge about mechanisms of change.

ClinicalTrials.gov NCT05931913. Registered prospectively on July 5, 2023.

Decision-making has been suggested as an endophenotype candidate for obsessive-compulsive disorder (OCD). However, few studies have examined whether decision-making under ambiguity is an endophenotype of OCD. This study aimed to investigate decision-making under ambiguity, as assessed by the Iowa Gambling Task (IGT), in patients with OCD and unaffected first-degree relatives (UFDR). Forty-seven non-medicated, non-co-morbid patients with OCD, 30 UFDR, and 47 healthy controls (HC) were compared in terms of decision-making using the IGT. The correlation between obsessive-compulsive symptoms and IGT performance was also investigated. Patients with OCD and UFDR performed worse than HC on the IGT. No correlation was found between obsessive-compulsive symptoms and IGT performance. A deficit in decision-making under ambiguity may be a trait and an endophenotype candidate for OCD.

Cognitive flexibility enables individuals to alter their behavior in response to changing environmental demands, facilitating optimal behavior in a dynamic world. The inability to do this, called behavioral inflexibility, is a pervasive behavioral phenotype in alcohol use disorder (AUD), driven by disruptions in cognitive flexibility. Research has repeatedly shown that behavioral inflexibility not only results from alcohol exposure across species but can itself be predictive of future drinking. Like many high-level executive functions, flexible behavior requires healthy functioning of the prefrontal cortex (PFC). The scope of this review addresses two primary themes: first, we outline tasks that have been used to investigate flexibility in the context of AUD or AUD models. We characterize these based on the task features and underlying cognitive processes that differentiate them from one another. We highlight the neural basis of flexibility measures, focusing on the PFC, and how acute or chronic alcohol in humans and non-human animal models impacts flexibility. Second, we consolidate findings on the molecular, physiological and functional changes in the PFC elicited by alcohol, that may contribute to cognitive flexibility deficits seen in AUD. Collectively, this approach identifies several key avenues for future research that will facilitate effective treatments to promote flexible behavior in the context of AUD, to reduce the risk of alcohol related harm, and to improve outcomes following AUD. This article is part of the Special Issue on "PFC circuit function in psychiatric disease and relevant models".

The link between autism spectrum disorder (ASD) and obsessive-compulsive disorder (OCD) and the complexity of their differential diagnosis has been vastly investigated. Growing attention has been paid to the presence of problematic Internet use (PIU) in autistic individuals. Studies assessing OCD traits in autistic individuals are scarce and even less take into account the role that this overlap may have on the development and maintenance of PIU. We aimed to investigate OCD features in ASD individuals and their association with autism severity and the prevalence of PIU, and the potential dimensions associated with a greater probability of PIU.

a total of 46 participants with ASD and 53 controls were assessed with the Adult Autism Subthreshold Spectrum questionnaire and the Obsessive-Compulsive Spectrum-Short Version.

There were significantly higher OCD features in ASD participants along with important correlations between OCD and ASD dimensions and a higher prevalence of PIU in the ASD group. Participants with putative PIU reported greater scores on some ASD and OCD dimensions, the with Doubt and Non-verbal communication domains emerging as significant predictors of the presence of putative PIU.

These results support the three-way link between ASD, OCD, and PIU, contributing to the hypothesis of a neurodevelopmental basis for those conditions.

Mental illnesses arise from dysfunction in the brain. Although numerous extraneural factors influence these illnesses, ultimately, it is the science of the brain that will lead to novel therapies. Meanwhile, our understanding of this complex organ is incomplete, leading to the oft-repeated trope that neuroscience has yet to make significant contributions to the care of individuals with mental illnesses. This review seeks to counter this narrative, using specific examples of how neuroscientific advances have contributed to progress in mental health care in the past and how current achievements set the stage for further progress in the future.

Previous research has found that compulsions in obsessive-compulsive disorder (OCD) are associated with an imbalance between goal-directed and habitual responses. However, the cognitive mechanisms underlying how goal-directed and habitual behaviors are learned, and how these learning deficits affect the response process, remain unclear. The present study aimed to investigate these cognitive mechanisms and examine how they were involved in the mechanism of compulsions.

A total of 49 patients with OCD and 38 healthy controls (HCs) were recruited to perform the revised "slip of action test". A reinforcement learning model was constructed, and model parameters including learning rates, reinforcement sensitivity, and perseveration were estimated using a hierarchical Bayesian approach. Comparisons of these parameters were made between the OCD group and HCs, and the associations with performance during the outcome devalued stage and clinical presentations were assessed.

In the outcome devalued stage, patients with OCD exhibited greatet responsiveness to the devalued outcome, indicating their impairment in flexible and goal-directed behavioral control. Computational modeling further revealed that, during the instrumental learning stage, patients with OCD showed reduced learning rates, decreased perseveration, and heightened reinforcement sensitivity as compared with HCs. The learning rate and perseveration during instrumental learning were significantly correlated with the performance in the outcome devalued stage and compulsive scores in OCD.

The results indicate that patients with OCD exhibit deficits in updating the associative strength based on prediction errors and are more likely to doubt established correct associations during goal-directed and habitual learning. These deficits may contribute to the inflexible goal-directed behavioral control and are involved in the mechanism of compulsion in OCD.

Chronic stress can change how we learn and, thus, how we make decisions. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted systems neuroscience approach in male and female mice, we reveal a dual pathway, amygdala-striatal neuronal circuit architecture by which a recent history of chronic stress disrupts the action-outcome learning underlying adaptive agency and promotes the formation of inflexible habits. We found that the basolateral amygdala projection to the dorsomedial striatum is activated by rewarding events to support the action-outcome learning needed for flexible, goal-directed decision making. Chronic stress attenuates this to disrupt action-outcome learning and, therefore, agency. Conversely, the central amygdala projection to the dorsomedial striatum mediates habit formation. Following stress this pathway is progressively recruited to learning to promote the premature formation of inflexible habits. Thus, stress exerts opposing effects on two amygdala-striatal pathways to disrupt agency and promote habit. These data provide neuronal circuit insights into how chronic stress shapes learning and decision making, and help understand how stress can lead to the disrupted decision making and pathological habits that characterize substance use disorders and mental health conditions.

A decoupling between confidence and action could relate to compulsive behaviour as seen in obsessive-compulsive disorder (OCD). The link between confidence and action in OCD has been investigated in clinical case-control studies and in the general population with discrepant findings. The generalizability of findings from highly-compulsive general population samples to clinical OCD samples has been questioned. Here, we investigate action-confidence coupling for 38 OCD patients compared to 37 healthy controls (HC), using a predictive inference task. We compared those results to a comparison between matched high and low compulsive individuals from the general population. Action-updating, confidence and their coupling were compared between the groups. Moreover, computational modeling was performed to compare groups on error sensitivity and environmental parameters. OCD patients showed lower confidence and higher learning rates in reaction to (small) prediction errors than HC, signaling hyperactive error signaling and lower confidence estimation. No evidence was found for differences in action-confidence coupling between groups. In contrast high the compulsive group showed higher confidence and stronger decoupling than the low compulsive group, both of which were related to symptoms. The underlying mechanisms of obsessive-compulsive behaviour might differ between clinical and highly-compulsive general population samples, resulting in different (meta)cognitive profiles.

This review explores the role of the antisaccadic task in understanding inhibitory mechanisms in basal ganglia disorders. It conducts a comparative analysis of saccadic profiles in conditions such as Parkinson's disease, Tourette syndrome, obsessive-compulsive disorder, Huntington's disease, and dystonia, revealing distinct patterns and proposing mechanisms for impaired performance. The primary focus is on two inhibitory mechanisms: global, pre-emptive inhibition responsible for suppressing prepotent responses, and slower, selective response inhibition. The antisaccadic task demonstrates practicality in clinical applications, aiding in differential diagnoses, treatment monitoring and reflecting gait control. To further enhance its differential diagnostic value, future directions should address issues such as the standardization of eye-tracking protocol and the integration of eye-tracking data with other disease indicators in a comprehensive dataset.

It is increasingly evident that structural and functional changes in brain regions associated with obsessive-compulsive disorder (OCD) are often related to the development of the disease. However, limited research has been conducted on how the progression of OCD may lead to an imbalance between goal-directed and habit-learning systems. This study employs resting-state functional imaging to examine the relationship between illness duration and abnormal brain function in goal-directed/habitual-learning systems. Demographic, clinical, and multimodal fMRI data were collected from participants. Our findings suggest that, compared to healthy controls, individuals with OCD exhibit abnormal brain functional indicators in both goal-directed and habit-learning brain regions, with a more pronounced reduction observed in the goal-directed regions. Additionally, abnormal brain activity is associated with illness duration, and the abnormalities observed in goal-directed regions are more effective in distinguishing different courses of OCD patients. Patients with different durations of OCD have functional abnormalities in the goal-directed and habitual-learning brain regions. There are differences in the degree of abnormality in different brain regions, and these abnormalities may disrupt the balance between goal-directed and habitual-learning systems, leading to increasing reliance on repetitive behaviors.

Dopamine modulates working memory in the prefrontal cortex (PFC) and is crucial for obsessive-compulsive disorder (OCD). However, the mechanism is unclear. Here we establish a biophysical model of the effect of dopamine (DA) in PFC to explain the mechanism of how high dopamine concentrations induce persistent neuronal activities with the network plunging into a deep, stable attractor state. The state develops a defect in working memory and tends to obsession and compulsion. Weakening the reuptake of dopamine acts on synaptic plasticity according to Hebbian learning rules and reward learning, which in turn affects the strength of neuronal synaptic connections, resulting in the tendency of compulsion and learned obsession. In addition, we elucidate the potential mechanisms of dopamine antagonists in OCD, indicating that dopaminergic drugs might be available for treatment, even if the abnormality is a consequence of glutamate hypermetabolism rather than dopamine. The theory highlights the significance of early intervention and behavioural therapies for obsessive-compulsive disorder. It potentially offers new approaches to dopaminergic pharmacotherapy and psychotherapy for OCD patients.

The balance between goal-directed and habitual control has been proposed to determine the flexibility of instrumental behaviour, in both humans and animals. This view is supported by neuroscientific studies that have implicated dissociable neural pathways in the ability to flexibly adjust behaviour when outcome values change. A previous Diffusion Tensor Imaging study provided preliminary evidence that flexible instrumental performance depends on the strength of parallel cortico-striatal white-matter pathways previously implicated in goal-directed and habitual control. Specifically, estimated white-matter strength between caudate and ventromedial prefrontal cortex correlated positively with behavioural flexibility, and posterior putamen-premotor cortex connectivity correlated negatively, in line with the notion that these pathways compete for control. However, the sample size of the original study was limited, and so far, there have been no attempts to replicate these findings. In the present study, we aimed to conceptually replicate these findings by testing a large sample of 205 young adults to relate cortico-striatal connectivity to performance on the slips-of-action task. In short, we found only positive neural correlates of goal-directed performance, including striatal connectivity (caudate and anterior putamen) with the dorsolateral prefrontal cortex. However, we failed to provide converging evidence for the existence of a neural habit system that puts limits on the capacity for flexible, goal-directed action. We discuss the implications of our findings for dual-process theories of instrumental action.

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 alcohol consumption remains a global public health crisis, with millions suffering from alcohol use disorder (AUD, or simply "alcoholism"), leading to significantly reduced life expectancy. This review examines the interplay between habitual and goal-directed behaviors and the associated neurobiological changes induced by chronic alcohol exposure. Contrary to a strict habit-goal dichotomy, our meta-analysis of the published animal experiments combined with a review of human studies reveals a nuanced transition between these behavioral control systems, emphasizing the need for refined terminology to capture the probabilistic nature of decision biases in individuals with a history of chronic alcohol exposure. Furthermore, we distinguish habitual responding from compulsivity, viewing them as separate entities with diverse roles throughout the stages of the addiction cycle. By addressing species-specific differences and translational challenges in habit research, we provide insights to enhance future investigations and inform strategies for combatting AUD.

The development of novel treatments for anorexia nervosa (AN) requires a detailed understanding of the biological underpinnings of specific, commonly occurring symptoms, including compulsive exercise. There is considerable bio-behavioral overlap between AN and obsessive-compulsive disorder (OCD), therefore it is plausible that similar mechanisms underlie compulsive behavior in both populations. While the association between these conditions is widely acknowledged, defining the shared mechanisms for compulsive behavior in AN and OCD requires a novel approach.

We present an argument that a better understanding of the neurobiological mechanisms that underpin compulsive exercise in AN can be achieved in two critical ways. First, by applying a framework of the neuronal control of OCD to exercise behavior in AN, and second, by taking better advantage of the activity-based anorexia (ABA) rodent model to directly test this framework in the context of feeding pathology.

A cross-disciplinary approach that spans preclinical, neuroimaging, and clinical research as well as compulsive neurocircuitry and behavior can advance our understanding of when, why, and how compulsive exercise develops in the context of AN and provide targets for novel treatment strategies.

In this article, we (i) link the expression of compulsive behavior in AN and OCD via a transition between goal-directed and habitual behavior, (ii) present disrupted cortico-striatal circuitry as a key substrate for the development of compulsive behavior in both conditions, and (iii) highlight the utility of the ABA rodent model to better understand the mechanisms of compulsive behavior relevant to AN.

Individuals with AN who exercise compulsively are at risk of worse health outcomes and have poorer responses to standard treatments. However, when, why, and how compulsive exercise develops in AN remains inadequately understood. Identifying whether the neural circuitry underlying compulsive behavior in OCD also controls hyperactivity in the activity-based anorexia model will aid in the development of novel eating disorder treatment strategies for this high-risk population.

Serotonin (5-HT) regulates working memory within the prefrontal cortex network, which is crucial for understanding obsessive-compulsive disorder. However, the mechanisms how network dynamics and serotonin interact in obsessive-compulsive disorder remain elusive. Here, we incorporate 5-HT receptors (5-HT1A, 5-HT2A) and dopamine receptors into a multistable prefrontal cortex network model, replicating the experimentally observed inverted U-curve phenomenon. We show how the two 5-HT receptors antagonize neuronal activity and modulate network multistability. Reduced binding of 5-HT1A receptors increases global firing, while reduced binding of 5-HT2A receptors deepens attractors. The obtained results suggest reward-dependent synaptic plasticity mechanisms may attenuate 5-HT related network impairments. Integrating serotonin-mediated dopamine release into circuit, we observe that decreased serotonin concentration triggers the network into a deep attractor state, expanding the domain of attraction of stable nodes with high firing rate, potentially causing aberrant reverse learning. This suggests a hypothesis wherein elevated dopamine concentrations in obsessive-compulsive disorder might result from primary deficits in serotonin levels. Findings of this work underscore the pivotal role of serotonergic dysregulation in modulating synaptic plasticity through dopamine pathways, potentially contributing to learned obsessions. Interestingly, serotonin reuptake inhibitors and antidopaminergic potentiators can counteract the over-stable state of high-firing stable points, providing new insights into obsessive-compulsive disorder treatment.

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.