On the effects of impulsivity and compulsivity on neural correlates of model-based performance.

Impaired goal-directed behavior is associated with a range of mental disorders, implicating underlying transdiagnostic factors. While compulsivity has been linked to reduced model-based (MB) control, impulsivity has rarely been studied in the context of reinforcement learning despite its links to reward processing and cognitive control. This study investigated the neural mechanisms underlying MB control and the influence of impulsivity and compulsivity, using EEG data from 238 individuals during a two-step decision making task. Single-trial analyses revealed a modulation of the feedback-related negativity (FRN), where amplitudes were higher after common transitions and positive reward prediction error (RPE), indicating a valence effect. Meanwhile, enhanced P3 amplitudes after rare transitions and both positive and negative RPE possibly reflect surprise. In a second step, we regressed the mean b values of the effect of RPE on the EEG signals onto self-reported impulsivity and compulsivity and behavioral MB control (w). The effect of RPE on FRN-related activity was mainly associated with higher w scores, linking the FRN to MB control. Crucially, the modulation of the P3 by RPE was negatively associated with compulsivity, pointing to a deficient mental model in highly compulsive individuals.

Correlation between compulsive behaviors and plastic changes in the dendritic spines of the prefrontal cortex and dorsolateral striatum of male rats.

Obsessive-compulsive disorder (OCD) is a mental affliction characterized by compulsive behaviors often manifested in intrusive thoughts and repetitive actions. The quinpirole model has been used with rats to replicate compulsive behaviors and study the neurophysiological processes associated with this pathology. Several changes in the dendritic spines of the medial prefrontal cortex (mPFC) and dorsolateral striatum (DLS) have been related to the occurrence of compulsive behaviors. Dendritic spines regulate excitatory synaptic contacts, and their morphology is associated with various brain pathologies. The present study was designed to correlate the occurrence of compulsive behaviors (generated by administering the drug quinpirole) with the morphology of the different types of dendritic spines in the mPFC and DLS. A total of 18 male rats were used. Half were assigned to the experimental group, the other half to the control group. The former received injections of quinpirole, while the latter rats were injected with physiological saline solution, for 10 days in both cases. After the experimental treatment, the quinpirole rats exhibited all the parameters indicative of compulsive behavior and a significant correlation with the density of stubby and wide neckless spines in both the mPFC and DLS. Dendritic spines from both mPFC and DLS neurons showed plastic changes correlatively with the expression of compulsive behavior induced by quinpirole. Further studies are suggested to evaluate the involvement of glutamatergic neurotransmission in the neurobiology of OCD.

Adult Offspring of Deer Mouse Breeding Pairs Selected for Normal and Compulsive-Like Large Nesting Expression Invariably Show the Same Behavior Without Prior In-Breeding.

Obsessive-compulsive disorder is a neuropsychiatric condition with notable genetic involvement. Against this background, laboratory-housed deer mice of both sexes varyingly present with excessive and persistent large nesting behavior (LNB), which has been validated for its resemblance of clinical compulsivity. Although LNB differs from normal nesting behavior (NNB) on both a biological and cognitive level, it is unknown to what extent the expression of LNB and NNB is related to familial background. Here, we randomly selected 14 NNB- and 14 LNB-expressing mice (equally distributed between sexes) to constitute 7 breeding pairs of each phenotype. Pairs were allowed to breed two successive generations of offspring, which were raised until adulthood (12 weeks) and assessed for nesting expression. Remarkably, our findings show that offspring from LNB-expressing pairs build significantly larger nests compared to offspring from NNB-expressing pairs and the nesting expression of the offspring of each breeding pair, irrespective of parental phenotype or litter, is family specific. Collectively, the results of this investigation indicate that LNB can be explored for its potential to shed light on heritable neurocognitive mechanisms that may underlie the expression of specific persistent behavioral phenotypes.

Experience-dependent grooming microstructure alterations and gastrointestinal dysfunction in the SAPAP3 knockout mouse model of compulsive behaviour.

BACKGROUND: Compulsive- and anxiety-like behaviour can be efficiently modelled in SAPAP3 knockout (KO) mice, a preclinical model of relevance to obsessive-compulsive disorder (OCD). Although there is emerging evidence in the clinical literature of gastrointestinal dysfunction in OCD, no previous studies have investigated gut function in preclinical models of relevance to OCD. Similarly, the effects of voluntary exercise (EX) or environmental enrichment (EE) have not yet been explored in this context. METHOD: We comprehensively phenotyped the SAPAP3 KO mouse model, including the assessment of grooming microstructure, anxiety- and depressive-like behaviour, and gastrointestinal function. Mice were exposed to either standard housing (SH), exercise (EX, provided by giving mice access to running wheels), or environmental enrichment (EE) for 4 weeks to investigate the effects of enriched housing conditions in this animal model relevant to OCD. FINDINGS: Our study is the first to assess grooming microstructure, perseverative locomotor activity, and gastrointestinal function in SAPAP3 KO mice. We are also the first to report a sexually dimorphic effect of grooming in young-adult SAPAP3 KO mice; along with changes to grooming patterning and indicators of gut dysfunction, which occurred in the absence of gut dysbiosis in this model. Overall, we found no beneficial effects of voluntary exercise or environmental enrichment interventions in this mouse model; and unexpectedly, we revealed a deleterious effect of wheel-running exercise on grooming behaviour. We suspect that the detrimental effects of experimental housing in our study may be indicative of off-target effects of stress-a conclusion that warrants further investigation into the effects of chronic stress in this preclinical model of compulsive behaviour.

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.

Confidence biases in problem gambling.

Background and aims: Subjective confidence plays an important role in guiding behaviour, especially when objective feedback is unavailable. Systematic misjudgements in confidence can foster maladaptive behaviours and have been linked to various psychiatric disorders. In this study, we adopted a transdiagnostic approach to examine confidence biases in problem gamblers across three levels: local decision confidence, global task performance confidence, and overall self-esteem. The importance of taking a transdiagnostic perspective is increasingly recognised, as it captures the dimensional nature of psychiatric symptoms that often cut across diagnostic boundaries. Accordingly, we investigated if any observed confidence biases could be explained by transdiagnostic symptom dimensions of Anxiety-Depression and Compulsive Behaviour and Intrusive Thought. This approach allows us to gain a more comprehensive understanding of the role of metacognitive processes in problem gambling, beyond the constraints of traditional diagnostic categories. Methods: Thirty-eight problem gamblers and 38 demographically matched control participants engaged in a gamified metacognition task and completed self-report questionnaires assessing transdiagnostic symptom dimensions. Results: Compared to controls, problem gamblers displayed significantly elevated confidence at the local decision and global task levels, independent of their actual task performance. This elevated confidence was observed even after controlling for the heightened symptom levels of Anxiety-Depression and Compulsive Behaviour and Intrusive Thought among the problem gamblers. Discussion: The results reveal a notable disparity in confidence levels between problem gamblers and control participants, not fully accounted for by the symptom dimensions Anxiety-Depression and Compulsive Behaviour and Intrusive Thought. This suggests the contribution of other factors, perhaps linked to gambling-specific cognitive distortions, to the observed confidence biases. Conclusion: The findings highlight the intricate link between metacognitive confidence and psychiatric symptoms in the context of problem gambling. It underscores the need for further research into metacognitive biases, which could enhance therapeutic approaches for individuals with psychiatric conditions.

Closed-loop recruitment of striatal interneurons prevents compulsive-like grooming behaviors.

Compulsive behaviors have been associated with striatal hyperactivity. Parvalbumin-positive striatal interneurons (PVIs) in the striatum play a crucial role in regulating striatal activity and suppressing prepotent inappropriate actions. To investigate the potential role of striatal PVIs in regulating compulsive behaviors, we assessed excessive self-grooming-a behavioral metric of compulsive-like behavior-in male Sapap3 knockout mice (Sapap3-KO). Continuous optogenetic activation of PVIs in striatal areas receiving input from the lateral orbitofrontal cortex reduced self-grooming events in Sapap3-KO mice to wild-type levels. Aiming to shorten the critical time window for PVI recruitment, we then provided real-time closed-loop optogenetic stimulation of striatal PVIs, using a transient power increase in the 1-4 Hz frequency band in the orbitofrontal cortex as a predictive biomarker of grooming onsets. Targeted closed-loop stimulation at grooming onsets was as effective as continuous stimulation in reducing grooming events but required 87% less stimulation time, paving the way for adaptive stimulation therapeutic protocols.

A molecularly defined orbitofrontal cortical neuron population controls compulsive-like behavior, but not inflexible choice or habit.

Habits are familiar behaviors triggered by cues, not outcome predictability, and are insensitive to changes in the environment. They are adaptive under many circumstances but can be considered antecedent to compulsions and intrusive thoughts that drive persistent, potentially maladaptive behavior. Whether compulsive-like and habit-like behaviors share neural substrates is still being determined. Here, we investigated mice bred to display inflexible reward-seeking behaviors that are insensitive to action consequences. We found that these mice demonstrate habitual response biases and compulsive-like grooming behavior that was reversible by fluoxetine and ketamine. They also suffer dendritic spine attrition on excitatory neurons in the orbitofrontal cortex (OFC). Nevertheless, synaptic melanocortin 4 receptor (MC4R), a factor implicated in compulsive behavior, is preserved, leading to the hypothesis that Mc4r+ OFC neurons may drive aberrant behaviors. Repeated chemogenetic stimulation of Mc4r+ OFC neurons triggered compulsive and not inflexible or habitual response biases in otherwise typical mice. Thus, Mc4r+ neurons within the OFC appear to drive compulsive-like behavior that is dissociable from habitual behavior. Understanding which neuron populations trigger distinct behaviors may advance efforts to mitigate harmful compulsions.

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

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

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

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

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

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

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

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

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

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

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

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

Disentangling associations between impulsivity, compulsivity, and performance monitoring.

Disorders marked by high levels of impulsivity and compulsivity have been linked to changes in performance monitoring, specifically the error-related negativity (ERN). We investigated the relationship between performance monitoring and individual differences in impulsivity and compulsivity. A total of 142 participants were recruited into four groups, each with different combinations of impulsivity and compulsivity, and they performed a flanker task to assess error-related brain activity. We defined error-related brain activity as ERN amplitude and theta power. Single-trial regression was employed to analyze the amplitude differences between incorrect and correct trials within the ERN time window. The findings revealed that impulsivity, compulsivity, and different measures of response processing exhibited distinct interactions, which were influenced by the configuration of impulsivity and compulsivity, but also depended on the measure of response processing. Specifically, high compulsivity predicted larger ERN amplitudes in individuals with low impulsivity, whereas high impulsivity had no significant effect on ERN amplitude in individuals with low compulsivity. Furthermore, when both impulsivity and compulsivity were high, no significant increase in ERN amplitude was observed; instead, there was a reduced difference between incorrect and correct trials. No significant differences were found for theta power. While the association between error-related brain activity and transdiagnostic markers or psychopathology may be smaller than generally assumed, considering the interaction between different transdiagnostic markers and their facets can enhance our understanding of the complex associations that arise during the investigation of neural correlates of performance monitoring, specifically the ERN.

A transdiagnostic and translational framework for delineating the neuronal mechanisms of compulsive exercise in anorexia nervosa.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. PUBLIC SIGNIFICANCE: 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.

A monster of a disease.

When compulsions and obsessive thoughts took over her world, a graduate student found strength in her identity as a scientist.

Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior in SAPAP3 knockout mice.

Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fast-acting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms underlying ketamine's therapeutic effect on OCD-like behaviors, we used the SAPAP3 knockout (KO) mouse model of compulsive grooming. Here we recapitulate the fast-acting therapeutic effect of ketamine on compulsive behavior, and show that ketamine increases activity of dorsomedial prefrontal neurons projecting to the dorsomedial striatum in KO mice. Optogenetically mimicking this increase in fronto-striatal activity reduced compulsive grooming behavior in KO mice. Conversely, inhibiting this circuit in wild-type mice increased grooming. Finally, we demonstrate that ketamine blocks the exacerbation of grooming in KO mice caused by optogenetically inhibiting fronto-striatal activity. These studies demonstrate that ketamine increases activity in a fronto-striatal circuit that causally controls compulsive grooming behavior, suggesting this circuit may be important for ketamine's therapeutic effects in OCD.

Predictors of short-term impulsive and compulsive behaviour after subthalamic stimulation in Parkinson disease.

BACKGROUND: The effects of subthalamic stimulation (subthalamic nucleus-deep brain stimulation, STN-DBS) on impulsive and compulsive behaviours (ICB) in Parkinson's disease (PD) are understudied. OBJECTIVE: To investigate clinical predictors of STN-DBS effects on ICB. METHODS: In this prospective, open-label, multicentre study in patients with PD undergoing bilateral STN-DBS, we assessed patients preoperatively and at 6-month follow-up postoperatively. Clinical scales included the Questionnaire for Impulsive-Compulsive Disorders in PD-Rating Scale (QUIP-RS), PD Questionnaire-8, Non-Motor Symptom Scale (NMSS), Unified PD Rating Scale in addition to levodopa-equivalent daily dose total (LEDD-total) and dopamine agonists (LEDD-DA). Changes at follow-up were analysed with Wilcoxon signed-rank test and corrected for multiple comparisons (Bonferroni method). We explored predictors of QUIP-RS changes using correlations and linear regressions. Finally, we dichotomised patients into 'QUIP-RS improvement or worsening' and analysed between-group differences. RESULTS: We included 55 patients aged 61.7 years±8.4 with 9.8 years±4.6 PD duration. QUIP-RS cut-offs and psychiatric assessments identified patients with preoperative ICB. In patients with ICB, QUIP-RS improved significantly. However, we observed considerable interindividual variability of clinically relevant QUIP-RS outcomes as 27.3% experienced worsening and 29.1% an improvement. In post hoc analyses, higher baseline QUIP-RS and lower baseline LEDD-DA were associated with greater QUIP-RS improvements. Additionally, the 'QUIP-RS worsening' group had more severe baseline impairment in the NMSS attention/memory domain. CONCLUSIONS: Our results show favourable ICB outcomes in patients with higher preoperative ICB severity and lower preoperative DA doses, and worse outcomes in patients with more severe baseline attention/memory deficits. These findings emphasise the need for comprehensive non-motor and motor symptoms assessments in patients undergoing STN-DBS. TRIAL REGISTRATION NUMBER: DRKS00006735.

White matter tracts characteristics in habitual decision-making circuit underlie ritual behaviors in anorexia nervosa.

Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships.