Selective decontamination of the digestive tract in burn patients: Protocol for a systematic review.

BACKGROUND: Nosocomial infections contribute significantly to mortality and morbidity in burn patients. Selective decontamination of the digestive tract is an infection prevention measure that has been shown to improve survival in mechanically ventilated intensive care unit (ICU) patients. It has been hypothesized that burn patients may benefit from selective decontamination of the digestive tract. METHODS/DESIGN: We will conduct a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials (RCTs) assessing the patient-important effects of selective decontamination of the digestive tract in burn patients, as compared with placebo or no intervention/standard of care. The primary outcome will be 30-day mortality. Secondary outcomes include serious adverse events, anti-microbial resistance, pneumonia, blood stream infections, ICU- and hospital-free days and 90-day mortality. We will search the following databases: CENTRAL, MEDLINE, EMBASE, BIOSIS, Web of Science and CINAHL and follow the recommendations provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The certainty of evidence will be assessed according to the GRADE approach: Grading of Recommendations Assessment, Development and Evaluation. DISCUSSION: There is clinical equipoise about the use of selective decontamination of the digestive tract in burn patients. In the outlined systematic review and meta-analysis, we will assess the desirable and undesirable effects of selective decontamination of the digestive tract in burn patients.

Attachment Problems and Mentalizing Capacity Relate to Parent-Child Informant Discrepancies in Female Adolescents with Borderline Personality Disorder.

Parent-child informant discrepancies on psychopathology provide important knowledge on the parent-child relationship and the child's mental health, but mechanisms underlying parent-child informant discrepancies are largely unknown. Therefore, we investigated the relationship between attachment problems and mentalizing capacity and parent-child informant discrepancies on borderline personality disorder (BPD) severity, internalizing, and externalizing pathology in a clinical sample of 91 adolescent girls with BPD and their parents. Results showed that more attachment problems to parents and peers were related to adolescents reporting more severe BPD than parents. Adolescents who described more internalizing symptoms relative to parents, reported more parental attachment problems, but enhanced peer attachment, suggesting those adolescents who do not feel recognized by their parents might turn to their friends. When parents rated adolescents higher on externalizing behaviors, the adolescent reported more attachment problems to parents and lower mentalizing capacity, indicating that this sub-group of adolescents may reflect less about how their behavior affects others.

Body Fit With a Pouching System With Concave Contour for People With an Outward Peristomal Body Profile: Effects on Leakage, Wear Time, and Quality of Life: A Randomized Controlled Cross-Over Trial.

PURPOSE: The purpose of the study was to investigate the fit of a two-piece pouching system with a concave-shaped skin barrier on people with an outward peristomal body profile and its effect on leakage, wear time, and quality of life (QoL) related to using an ostomy product. DESIGN: Randomized, controlled, open-label, cross-over trial. SUBJECTS AND SETTINGS: The sample comprised 53 subjects with outward peristomal body profiles and problems with leakage of ostomy effluent from their pouching system. Participants were randomized to the concave two-piece pouching system or a comparator (two-piece pouching system with a flat skin barrier) for 3 weeks. Subjects were then crossed over to the opposite skin barrier for an additional 3 weeks. The study was conducted in Denmark, Norway, Germany, and the Netherlands; data were collected in multiple ambulatory clinics or during home visits. METHODS: The primary end point was the ability of the skin barrier to fit body contours; secondary outcomes were leakage of effluent from the pouching system, wear time, and QoL related to using an ostomy product via the validated Ostomy-Q questionnaire. Primary comparisons between concave and comparator pouching systems were evaluated using proportional odds models and mixed models taking test period into account. RESULTS: Analysis included randomized subjects who had been exposed to at least one product and with information on at least one end point (full-analysis-set, n = 52). The concave pouching system provided a better fit to body contours than the comparator (P< .001) and reduced the degree of leakage underneath the skin barrier (LS mean difference = -1.84, 95% CI -3.31 to -0.37; P = .016). Participants experienced fewer episodes of leakage outside the skin barrier when using concave versus comparator pouching system (13.0% vs. 26.7%, respectively). Participants reported significant improvements in QoL (LS mean difference = 14.3; 95% CI 9.4 to 19.2; P < .001). No significant difference in wear time between skin barrier shapes was reported. CONCLUSIONS: Study findings indicate that a pouching system with a concave skin barrier achieved a better body fit on people with an outward peristomal body profile and resulted in fewer leakage incidents and higher QoL compared to using a pouching system with a flat skin barrier.

Importance of stoma care nurses in preparing patients for stoma surgery and adjustment to life with a stoma.

BACKGROUND: Stoma surgery is a life-changing event and patients must subsequently make significant adjustments to their lives. AIM: The study set out to understand the level of interaction between patients and stoma care nurses (SCNs) in relation to preparing patients for stoma surgery and in adjustment to life with a stoma. METHODS: Retrospective, self-reported questionnaires for patients and SCNs. FINDINGS: Most patients (98%) with planned stoma surgery had pre-operative consultations with health professionals in contrast to 36% of patients with unplanned surgery, who did not. One third of patients with unplanned surgery did not feel prepared for life with a stoma based on the information provided during their hospital stay. Two thirds of the nurses reported having sufficient time to prepare patients for stoma surgery and to life with a stoma. CONCLUSION: SCNs are key in preparing patients for surgery and for life with a stoma. Variations in care were experienced by patients having planned versus unplanned surgeries.

Leakage of stomal effluent outside the baseplate leads to rise in product usage and health professional interactions.

BACKGROUND: Leakage of stomal effluent outside the baseplate that soils clothes or bedsheets is a common problem for many people with a stoma and significantly impacts their quality of life. AIM: To understand behavioural changes for people experiencing faecal leakage outside the baseplate regarding the usage of pouching systems, supporting products and interactions with health professionals. METHODS: Retrospective, self-reported questionnaire. FINDINGS: Respondents on average experienced 1.1 incidents of faecal leakage outside the baseplate per fortnight. In periods with issues of leakage, 21% of respondents had been in contact with health professionals, 40% increased their use of pouching systems, 25% increased their use of existing supporting products, and 21% included additional supporting products to their change routine. The increased use of healthcare resources was estimated to cost £32.47 in the 3 weeks following a leakage incident. CONCLUSION: Incidents of leakage outside the baseplate lead to increased use of healthcare resources.

A pilot study of a digital ostomy leakage notification system: impact on worry and quality of life.

BACKGROUND: More than 90% of people with an ostomy worry about leakage, with associated high rates of psychological morbidity. AIMS: To assess the performance of a novel digital ostomy leakage notification system in subjects with faecal stomas who experience and worry about leakage. METHOD: A prospective, single-arm, pilot study (ClinicalTrials.gov: NCT04894084) with 25 subjects testing the product for 21 days. Subjects completed questionnaires at baseline and termination of study evaluating leakage episodes, leakage worry and quality of life (QoL). FINDINGS: Mean age was 56 years, 60% had an ileostomy, and 40% were females. Mean episodes of leakage outside the baseplate decreased significantly from 2.8 to 0.5 episodes after 21 days' use of the test product (P<0.001), worry about leakage decreased significantly (P<0.001) and QoL improved. CONCLUSION: The findings indicate strong improvements to emotional health with the test product, driven by reductions in leakage incidents outside baseplate and in users' worry about leakage.

Glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with differences in uncinate fasciculus microstructure.

BACKGROUND: Evidence suggests that fronto-limbic brain regions and connecting white matter fibre tracts in the left hemisphere are more sensitive to glucocorticoids than in the right hemisphere. It is unknown whether treatment with glucocorticoids in childhood is associated with microstructural differences of the uncinate fasciculus and cingulum bundle, which connect fronto-limbic brain regions. Here, we tested the hypothesis that prior glucocorticoid treatment would be associated with differences in fractional anisotropy (FA) of the left relative to right uncinate fasciculus and cingulum bundle. METHODS: We performed diffusion-weighted imaging in 28 children and adolescents aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disease and 28 healthy controls. RESULTS: Patients displayed significantly different asymmetry in the microstructure of uncinate fasciculus with higher left but similar right uncinate fasciculus FA and axial diffusivity compared to controls. No apparent differences were observed for the cingulum. Notably, higher cumulative glucocorticoid doses were significantly associated with higher uncinate fasciculus FA and axial diffusivity bilaterally. CONCLUSIONS: Our findings indicate that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in the microstructure of the uncinate fasciculi, and that higher cumulative glucocorticoid doses have a proportional impact on the microstructure. IMPACT: It is unknown if treatment with glucocorticoids in childhood have long-term effects on fronto-limbic white matter microstructure. The study examined if children and adolescents previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder differed in fronto-limbic white matter microstructure compared to healthy controls. The nephrotic and rheumatic patients had higher left but similar right uncinate fasciculus FA and axial diffusivity. Higher bilateral uncinate fasciculus FA and axial diffusivity was associated with higher cumulative glucocorticoid doses. We revealed new evidence suggesting that previous glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with long-term changes in uncinate fasciculi microstructure.

Prevalence of leakage and its negative impact on quality of life in people living with a stoma in the UK.

BACKGROUND: People with a stoma are reported to experience leakage, which negatively impacts patient quality of life (QoL). AIM: To assess the impact of leakage experienced by individuals with a stoma in the UK. METHODS: Data were analysed from 301 patients living in the UK who completed a questionnaire concerning the physical and psychosocial impact of living with a stoma. FINDINGS: Most respondents had had their stoma for more than 5 years. Nine out of 10 worried about leakage to varying degrees and half the respondents accepted that this was a worry they had to live with. Almost 70% experienced leakage onto clothes within the preceding year, and 28% experienced this monthly. Peristomal skin complications were experienced by 82% of respondents, the severity of which correlated with reductions in QoL. CONCLUSION: Despite the consequential negative impact of leakage on QoL, individuals are not seeking advice to resolve leakage-related issues, including from their specialist stoma care nurse.

Impact of stoma leakage in everyday life: data from the Ostomy Life Study 2019.

BACKGROUND: Many people with a stoma experience leakage of stomal effluent. AIM: To investigate the impact of leakage on individuals with a stoma. METHODS: The Ostomy Life Study 2019 included a survey concerning experiences with stomal effluent leakage and the validated Ostomy Leak Impact tool. FINDINGS: Respondents with frequent leakage episodes were significantly more affected emotionally and they were feeling less in control than those who rarely or never experienced leakage. The emotional impact of experiencing leakage onto clothes appeared to last up to 1 year after the last leakage incidence. Because of worrying about leakage users increased their product usage and, of those who were in employment, 65% reported that leakage and the related worry influenced their ability to work. CONCLUSION: Most people with a stoma were emotionally impacted by experiencing leakage, especially by leakage outside the baseplate (resulting in soiled clothes). New solutions are warranted that can help reduce the impact of leakage.

Retrospective Valuation of Experienced Outcome Encoded in Distinct Reward Representations in the Anterior Insula and Amygdala.

Our ability to evaluate an experience retrospectively is important because it allows us to summarize its total value, and this summary value can then later be used as a guide in deciding whether the experience merits repeating, or whether instead it should rather be avoided. However, when an experience unfolds over time, humans tend to assign disproportionate weight to the later part of the experience, and this can lead to poor choice in repeating, or avoiding experience. Using model-based computational analyses of fMRI recordings in 27 male volunteers, we show that the human brain encodes the summary value of an extended sequence of outcomes in two distinct reward representations. We find that the overall experienced value is encoded accurately in the amygdala, but its merit is excessively marked down by disincentive anterior insula activity if the sequence of experienced outcomes declines temporarily. Moreover, the statistical strength of this neural code can separate efficient decision-makers from suboptimal decision-makers. Optimal decision-makers encode overall value more strongly, and suboptimal decision-makers encode the disincentive markdown (DM) more strongly. The separate neural implementation of the two distinct reward representations confirms that suboptimal choice for temporally extended outcomes can be the result of robust neural representation of a displeasing aspect of the experience such as temporary decline.SIGNIFICANCE STATEMENT One of the numerous foibles that prompt us to make poor decisions is known as the "Banker's fallacy," the tendency to focus on short-term growth at the expense of long-term value. This effect leads to unwarranted preference for happy endings. Here, we show that the anterior insula in the human brain marks down the overall value of an experience as it unfolds over time if the experience entails a sequence of predominantly negative temporal contrasts. By contrast, the amygdala encodes overall value accurately. These results provide neural indices for the dichotomy of decision utility and experienced utility popularized as Thinking fast and slow by Daniel Kahneman.

Exploring Identity Disturbance and Psychotic Spectrum Symptoms as Predictors of Borderline and Schizotypal Personality Disorders.

INTRODUCTION: Borderline personality disorder (BPD) and schizotypal personality disorder (SPD) were introduced in DSM-III and retained in DSM-5 Section II. They often co-occur and some aspects of the clinical differentiation between the 2 diagnoses remain unclear (e.g., psychotic-like features and identity disturbance). METHODS: The present study explored if self-reported identity disturbance and psychosis proneness could discriminate between the BPD and SPD DSM-5 diagnoses. All patients were interviewed with the Schedules for Clinical Assessment in Neuropsychiatry and the Structured Clinical Interview for DSM-5 Personality Disorders, and administered the Inventory of Personality Organization, Self-Concept and Identity Measure, Schizotypal Personality Questionnaire, Perceptual Aberration Scale, and the Magical Ideation Scale. RESULTS: A total of 105 patients were initially assessed, 26 were excluded, and the final sample (N = 79) was composed of 34 BPD patients, 25 SPD patients, and 20 patients with co-occurring SPD and BPD. The BPD group (n = 34) was first compared with the pure SPD group (n = 25), and secondly with the total group of patients diagnosed with SPD (n = 25 + 20). Logistic regression analyses indicated that primitive defenses and disorganization best differentiated the BPD and the pure SPD group, while primitive defenses and interpersonal factor along with perceptual aberrations best differentiated the BPD and the total SPD group. CONCLUSION: Identity disturbance did not predict the diagnostic groups, but BPD patients were characterized by primitive defenses, which are closely related to identity disturbance. Pure SPD was characterized by oddness/eccentricity, while the lack of specificity for cognitive-perceptual symptoms suggests that the positive symptoms do not differentiate BPD from SPD.

Peptide/ß-Peptoid Hybrids with Activity against Vancomycin-Resistant Enterococci: Influence of Hydrophobicity and Structural Features on Antibacterial and Hemolytic Properties.

Infections with enterococci are challenging to treat due to intrinsic resistance to several antibiotics. Especially vancomycin-resistant Enterococcus faecium and Enterococcus faecalis are of considerable concern with a limited number of efficacious therapeutics available. From an initial screening of 20 peptidomimetics, 11 stable peptide/ß-peptoid hybrids were found to have antibacterial activity against eight E. faecium and E. faecalis isolates. Microbiological characterization comprised determination of minimal inhibitory concentrations (MICs), probing of synergy with antibiotics in a checkerboard assay, time-kill studies, as well as assessment of membrane integrity. E. faecium isolates proved more susceptible than E. faecalis isolates, and no differences in susceptibility between the vancomycin-resistant (VRE) and -susceptible E. faecium isolates were observed. A test of three peptidomimetics (Ac-[hArg-ßNsce]6-NH2, Ac-[hArg-ßNsce-Lys-ßNspe]3-NH2 and Oct-[Lys-ßNspe]6-NH2) in combination with conventional antibiotics (vancomycin, gentamicin, ciprofloxacin, linezolid, rifampicin or azithromycin) revealed no synergy. The same three potent analogues were found to have a bactericidal effect with a membrane-disruptive mode of action. Peptidomimetics Ac-[hArg-ßNsce-Lys-ßNspe]3-NH2 and Oct-[Lys-ßNspe]6-NH2 with low MIC values (in the ranges 2-8 µg/mL and 4-16 µg/mL against E. faecium and E. faecalis, respectively) and displaying weak cytotoxic properties (i.e., <10% hemolysis at a ~100-fold higher concentration than their MICs; IC50 values of 73 and 41 µg/mL, respectively, against HepG2 cells) were identified as promising starting points for further optimization studies.

Predictors of dropout among adolescents with borderline personality disorder attending mentalization-based group treatment.

Background: Premature termination from treatment or dropout is prevalent among patients with borderline personality disorder (BPD). To our knowledge, no studies have examined which factors predisposes dropout from therapy among adolescents with BPD. The current study examined sociodemographic, clinical and psychological predictors of dropout among adolescents who attended a one-year treatment program with mentalization-based group treatment (MBT-G).Methods: Participants were 89 female adolescent patients aged 14-18 years who attended MBT-G in a Danish child and adolescent psychiatric service and 56 matched controls who received non-manualized individual sessions (treatment as usual). Forty (45%) dropped out and 49 (55%) completed treatment in MBT-G. Pretreatment predictors included (1) sociodemographic variables such as age, schooling, relationship status and after-school job, (2) clinical measures of self-reported adolescent borderline personality features, depression, self-harm, internalizing and externalizing symptoms, and (3) psychological measures on self-reported reflective functioning (i.e., mentalizing) and attachment to peers and parents.Results: Binary logistic regression analyses revealed that lower reflective functioning was the only significant predictor of dropout in MBT-G. No sociodemographic or clinical variables predicted dropout. No significant predictors of dropout were identified among participants who received treatment as usual.Conclusions: Adolescents with BPD who report low reflective functioning are at increased risk of dropping out of MBT-G treatment but not treatment as usual. These findings highlight that clinicians need to consider level of reflective functioning among adolescents with BPD in MBT or in group therapy and adapt psychotherapy to the needs of the patient in order to reduce dropout.

Perception of leakage: data from the Ostomy Life Study 2019.

BACKGROUND: Leakage is a common problem for people with a stoma. AIM: To investigate how people with a stoma and stoma care nurses perceive different patterns of effluent under the baseplate. METHODS: The Ostomy Life Study 2019 included a user survey and a nurse survey covering experiences of leakage and the perception of leakage. FINDINGS: Most people with a stoma perceived effluent reaching outside the baseplate as leakage (88-90%), whereas effluent close to the stoma only was not perceived as leakage by the majority (81-91%). Effluent covering major parts of the baseplate was perceived as leakage by most respondents with a colostomy or ileostomy (83%), whereas fewer respondents with a urostomy perceived this as leakage (57%). Most of the nurses (70%) did not perceive effluent close to the stoma as leakage. CONCLUSION: This study revealed that effluent confined to the area next to the stoma is generally not perceived as leakage.

Dopamine Modulates Adaptive Prediction Error Coding in the Human Midbrain and Striatum.

Learning to optimally predict rewards requires agents to account for fluctuations in reward value. Recent work suggests that individuals can efficiently learn about variable rewards through adaptation of the learning rate, and coding of prediction errors relative to reward variability. Such adaptive coding has been linked to midbrain dopamine neurons in nonhuman primates, and evidence in support for a similar role of the dopaminergic system in humans is emerging from fMRI data. Here, we sought to investigate the effect of dopaminergic perturbations on adaptive prediction error coding in humans, using a between-subject, placebo-controlled pharmacological fMRI study with a dopaminergic agonist (bromocriptine) and antagonist (sulpiride). Participants performed a previously validated task in which they predicted the magnitude of upcoming rewards drawn from distributions with varying SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. Under placebo, we replicated previous observations of adaptive coding in the midbrain and ventral striatum. Treatment with sulpiride attenuated adaptive coding in both midbrain and ventral striatum, and was associated with a decrease in performance, whereas bromocriptine did not have a significant impact. Although we observed no differential effect of SD on performance between the groups, computational modeling suggested decreased behavioral adaptation in the sulpiride group. These results suggest that normal dopaminergic function is critical for adaptive prediction error coding, a key property of the brain thought to facilitate efficient learning in variable environments. Crucially, these results also offer potential insights for understanding the impact of disrupted dopamine function in mental illness.SIGNIFICANCE STATEMENT To choose optimally, we have to learn what to expect. Humans dampen learning when there is a great deal of variability in reward outcome, and two brain regions that are modulated by the brain chemical dopamine are sensitive to reward variability. Here, we aimed to directly relate dopamine to learning about variable rewards, and the neural encoding of associated teaching signals. We perturbed dopamine in healthy individuals using dopaminergic medication and asked them to predict variable rewards while we made brain scans. Dopamine perturbations impaired learning and the neural encoding of reward variability, thus establishing a direct link between dopamine and adaptation to reward variability. These results aid our understanding of clinical conditions associated with dopaminergic dysfunction, such as psychosis.

Total brain, cortical, and white matter volumes in children previously treated with glucocorticoids.

BackgroundPerinatal exposure to glucocorticoids and elevated endogenous glucocorticoid levels during childhood can have detrimental effects on the developing brain. Here, we examined the impact of glucocorticoid treatment during childhood on brain volumes.MethodsA total of 30 children and adolescents with rheumatic or nephrotic disease previously treated with glucocorticoids and 30 controls matched on age, sex, and parent education underwent magnetic resonance imaging (MRI) of the brain. Total cortical gray and white matter, brain, intracranial volume, and total cortical thickness and surface area were derived from MRI scans.ResultsPatients had significantly smaller gray and white matter and total brain volumes relative to healthy controls. Brain volume differences disappeared when accounting for intracranial volume, as patients had relatively smaller intracranial volumes. Group differences were mainly driven by the children with rheumatic disease. Total cortical thickness and cortical surface area did not significantly differ between groups. We found no significant associations between glucocorticoid-treatment variables and volumetric measures.ConclusionObserved smaller total brain, cortical gray, and white matter volumes in children and adolescents previously treated with glucocorticoids compared with that in healthy controls may reflect both developmental and degenerative processes. Prospective longitudinal studies are warranted to clarify whether findings are related to treatment or disease.

Antimicrobial peptide exposure selects for Staphylococcus aureus resistance to human defence peptides.

BACKGROUND: The clinical development of antimicrobial peptides (AMPs) is currently under evaluation to combat the rapid increase in MDR bacterial pathogens. However, many AMPs closely resemble components of the human innate immune system and the ramifications of prolonged bacterial exposure to AMPs are not fully understood. OBJECTIVES: We show that in vitro serial passage of a clinical USA300 MRSA strain in a host-mimicking environment containing host-derived AMPs results in the selection of stable AMP resistance. METHODS: Serial passage experiments were conducted using steadily increasing concentrations of LL-37, PR-39 or wheat germ histones. WGS and proteomic analysis by MS were used to identify the molecular mechanism associated with increased tolerance of AMPs. AMP-resistant mutants were characterized by measuring in vitro fitness, AMP and antibiotic susceptibility, and virulence in a mouse model of sepsis. RESULTS: AMP-resistant Staphylococcus aureus mutants often displayed little to no fitness cost and caused invasive disease in mice. Further, this phenotype coincided with diminished susceptibility to both clinically prescribed antibiotics and human defence peptides. CONCLUSIONS: These findings suggest that therapeutic use of AMPs could select for virulent mutants with cross-resistance to human innate immunity as well as antibiotic therapy. Thus, therapeutic use of AMPs and the implications of cross-resistance need to be carefully monitored and evaluated.

Glucocorticoid treatment earlier in childhood and adolescence show dose-response associations with diurnal cortisol levels.

Heightened levels of glucocorticoids in children and adolescents have previously been linked to prolonged changes in the diurnal regulation of the stress-hormone cortisol, a glucocorticoid regulated by the hypothalamic-pituitary-adrenal-axis (HPA-axis). To address this question, we examined the salivary cortisol awakening response (CAR) and daily cortisol output in 36 children and adolescents (25 girls/11 boys) aged 7-16 years previously treated with glucocorticoids for nephrotic syndrome or rheumatic disorder and 36 healthy controls. Patients and controls did not significantly differ in the CAR or diurnal cortisol output; however, sex-dependent group differences were observed. Specifically, female patients had a higher CAR relative to female controls, while male patients had higher daily cortisol levels compared to male controls. Notably, CAR in female patients and daily cortisol levels in male patients showed a positive linear relationship with the mean daily glucocorticoid doses administered during treatment. The observed dose-response associations suggest that glucocorticoid therapy during childhood and adolescence might trigger long-term changes in HPA-axis regulation, which may differ for males and females.

Imbalance in habitual versus goal directed neural systems during symptom provocation in obsessive-compulsive disorder.

Intrusive thoughts and compulsive urges to perform stereotyped behaviours are typical symptoms of obsessive-compulsive disorder. Emerging evidence suggests a cognitive bias towards habit formation at the expense of goal-directed performance in obsessive-compulsive disorder. In this study, we test this hypothesis using a novel individualized ecologically valid symptom provocation design: a live provocation functional magnetic resonance imaging paradigm with synchronous video-recording of behavioural avoidance responses. By pairing symptom provocation with online avoidance responses on a trial-by-trial basis, we sought to investigate the neural mechanisms leading to the compulsive avoidance response. In keeping with the model of habit formation in obsessive-compulsive disorder, we hypothesized that this disorder would be associated with lower activity in regions implicated in goal-directed behaviours and higher activity in regions implicated in habitual behaviours. Fifteen patients with obsessive-compulsive disorder and 15 healthy control volunteers participated in this functional magnetic resonance imaging study. Online stimuli were individually tailored to achieve effective symptom provocation at neutral, intermediate and strong intensity levels. During the symptom provocation block, the participant could choose to reject or terminate the provoking stimuli resulting in cessation of the symptom provocation. We thus separately analysed the neural correlates of symptom provocation, the urge to avoid, rejection and relief. Strongly symptom-provoking conditions evoked a dichotomous pattern of deactivation/activation in patients, which was not observed either in control conditions or in healthy subjects: a deactivation of caudate-prefrontal circuits accompanied by hyperactivation of subthalamic nucleus/putaminal regions. This finding suggests a dissociation between regions engaged in goal-directed and habitual behaviours. The putaminal hyperactivity during patients' symptom provocation preceded subsequent deactivation during avoidance and relief events, indicating a pivotal role of putamen in regulation of behaviour and habit formation in obsessive-compulsive disorder. Effective connectivity analysis identified the ventromedial prefrontal cortex/orbitofrontal cortex as the main structure in this circuitry involved in the modulation of compulsivity in obsessive-compulsive disorder. These findings suggest an imbalance in circuitry underlying habitual and goal-directed action control, which may represent a fundamental mechanism underlying compulsivity in obsessive-compulsive disorder. Our results complement current models of symptom generation in obsessive-compulsive disorder and may enable the development of future therapeutic approaches that aim to alleviate this imbalance.