Fronto-striatal circuits in response-inhibition: Relevance to addiction.

Disruptions to inhibitory control are believed to contribute to multiple aspects of drug abuse, from preexisting vulnerability in at-risk individuals, through escalation to dependence, to promotion of relapse in chronic users. Paradigms investigating the suppression of actions have been investigated in animal and human research on drug addiction. Rodent research has focused largely on impulsive behaviors, often gauged by premature responding, as a viable model highlighting the relevant role of dopamine and other neurotransmitters primarily in the striatum. Human research on action inhibition in stimulant dependence has highlighted impaired performance and largely prefrontal cortical abnormalities as part of a broader pattern of cognitive abnormalities. Animal and human research implicate inhibitory difficulties mediated by fronto-striatal circuitry both preceding and as a result of excessive stimulus use. In this regard, response-inhibition has proven a useful cognitive function to gauge the integrity of fronto-striatal systems and their role in contributing to impulsive and compulsive features of drug dependence.This is the final version. It was first published by Elsevier at http://dx.doi.org/10.1016/j.brainres.2014.09.01

Stopping a Response When You Really Care about the Action: Considerations from a Clinical Perspective

Response inhibition, whether reactive or proactive, is mostly investigated in a narrow cognitive framework. We argue that it be viewed within a broader frame than the action being inhibited, i.e., in the context of emotion and motivation of the individual at large. This is particularly important in the clinical domain, where the motivational strength of an action can be driven by threat avoidance or reward seeking. The cognitive response inhibition literature has focused on stopping reactively with responses in anticipation of clearly delineated external signals, or proactively in limited contexts, largely independent of clinical phenomena. Moreover, the focus has often been on stopping efficiency and its correlates rather than on inhibition failures. Currently, the cognitive and clinical perspectives are incommensurable. A broader context may explain the apparent paradox where individuals with disorders characterised by maladaptive action control have difficulty inhibiting their actions only in specific circumstances. Using Obsessive Compulsive Disorder as a case study, clinical theorising has focused largely on compulsions as failures of inhibition in relation to specific internal or external triggers. We propose that the concept of action tendencies may constitute a useful common denominator bridging research into motor, emotional, motivational, and contextual aspects of action control failure. The success of action control may depend on the interaction between the strength of action tendencies, the ability to withhold urges, and contextual factors

Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence

A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption

Shining a Light on a Hidden Population: Social Functioning and Mental Health in Women Reporting Autistic Traits But Lacking Diagnosis

Female Phenotype Theory (FPT) suggests that autistic women often present with less obvious social impairments than autistic men. We examined the possibility of an exaggerated female phenotype among undiagnosed but probably autistic women. In two nationwide online surveys, we compared self-reported social functioning and mental health between diagnosed autistic women and women without diagnosis who scored ≥ 32 on the Autism Quotient. Compared to diagnosed autistic women, probably autistic women had higher empathy and general social functioning, and were more likely to have received a diagnosis of Borderline Personality Disorder. Autistic women had typically received more mental health diagnoses prior to their ASC diagnosis than autistic men. These findings shed light on the history of misdiagnosis experienced by many autistic women

Free operant observing in humans: a translational approach to compulsive certainty seeking

Excessive checking is reported in non-clinical populations and is a pervasive symptom in Obsessive Compulsive Disorder (OCD). We implemented a free-operant task in humans, previously used in rats, wherein participants can “check” to reduce uncertainty. Participants can press an observing key to ascertain which of two main keys will, if pressed, currently lead to rewards. Over a series of experiments we found that punishment robustly increased observing in non-clinical participants and that observing persisted long after punishment was removed. Moreover, participants appeared insensitive to the initial costs of checking, and a threefold increase in the effort required to observe served to deter participants only to a limited degree. We also assessed observing in OCD patients with no known comorbidities. The patients observed more than control participants and were abnormally insensitive to the introduction of punishment. These findings support the translational value of the task, with similar behaviours in humans and rodents. This paradigm may serve as a unifying platform, promoting interaction between different approaches to analyze adaptive and maladaptive certainty seeking behaviours. Specifically, we demonstrate how seemingly disparate theoretical and empirical approaches can be reconciled synergistically to promote a combined behavioural and cognitive account of certainty seeking.This research was supported by a grant from the Wellcome Trust to TW Robbins (104631/Z/14/Z)

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

BACKGROUND: Youths with obsessive-compulsive disorder (OCD) experience severe distress and impaired functioning at school and at home. Critical cognitive domains for daily functioning and academic success are learning, memory, cognitive flexibility and goal-directed behavioural control. Performance in these important domains among teenagers with OCD was therefore investigated in this study. METHODS: A total of 36 youths with OCD and 36 healthy comparison subjects completed two memory tasks: Pattern Recognition Memory (PRM) and Paired Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED) task to quantitatively gauge learning as well as cognitive flexibility. A subset of 30 participants of each group also completed a Differential-Outcome Effect (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of goal-directed and habitual behavioural control. RESULTS: Adolescent OCD patients showed a significant learning and memory impairment. Compared with healthy comparison subjects, they made more errors on PRM and PAL and in the first stages of IED involving discrimination and reversal learning. Patients were also slower to learn about contingencies in the DOE task and were less sensitive to outcome devaluation, suggesting an impairment in goal-directed control. CONCLUSIONS: This study advances the characterization of juvenile OCD. Patients demonstrated impairments in all learning and memory tasks. We also provide the first experimental evidence of impaired goal-directed control and lack of cognitive plasticity early in the development of OCD. The extent to which the impairments in these cognitive domains impact academic performance and symptom development warrants further investigation.This work was funded by a Wellcome Trust Grant (grant number 089589/Z/09/Z) awarded to TW Robbins, BJ Everitt, AC Roberts, JW Dalley, and BJ Sahakian, and a Wellcome Trust Senior Investigator Award (104631/Z/14/Z) to TW Robbins. The research was conducted in the Behavioural and Clinical Neuroscience Institute, which is supported by a joint award from the Medical Research Council and Wellcome Trust (G00001354). J Gottwald was supported by a BCNI MRC PhD studentship and St John’s College, Cambridge

Measuring “waiting” impulsivity in substance addictions and binge eating disorder in a novel analogue of rodent serial reaction time task

Background Premature responding is a form of motor impulsivity that preclinical evidence has shown to predict compulsive drug seeking but has not yet been studied in humans. We developed a novel translation of the task, based on the rodent 5-choice serial reaction time task, testing premature responding in disorders of drug and natural food rewards. Methods Abstinent alcohol- (n = 30) and methamphetamine-dependent (n = 23) subjects, recreational cannabis users (n = 30), and obese subjects with (n = 30) and without (n = 30) binge eating disorder (BED) were compared with matched healthy volunteers and tested on the premature responding task. Results Compared with healthy volunteers, alcohol- and methamphetamine-dependent subjects and cannabis users showed greater premature responding with no differences observed in obese subjects with or without BED. Current smokers exhibited greater premature responding versus ex-smokers and nonsmokers. Alcohol-dependent subjects also had lower motivation for explicit monetary incentives. A Motivation Index correlated negatively with alcohol use and binge eating severity. Conclusions Premature responding on a novel translation of a serial reaction time task was more evident in substance use disorders but not in obese subjects with or without BED. Lower motivation for monetary incentives linked alcohol use and binge eating severity. Our findings add to understanding the relationship between drug and natural food rewards

The profile of executive function in OCD hoarders and hoarding disorder

Hoarding disorder is a new mental disorder in DSM-5. It is classified alongside OCD and other presumably related disorders in the Obsessive-Compulsive and Related Disorders chapter. We examined cognitive performance in two distinct groups comprising individuals with both OCD and severe hoarding, and individuals with hoarding disorder without comorbid OCD. Participants completed executive function tasks assessing inhibitory control, cognitive flexibility, spatial planning, probabilistic learning and reversal and decision making. Compared to a matched healthy control group, OCD hoarders showed significantly worse performance on measures of response inhibition, set shifting, spatial planning, probabilistic learning and reversal, with intact decision making. Despite having a strikingly different clinical presentation, individuals with only hoarding disorder did not differ significantly from OCD hoarders on any cognitive measure suggesting the two hoarding groups have a similar pattern of cognitive difficulties. Tests of cognitive flexibility were least similar across the groups, but differences were small and potentially reflected subtle variation in underlying brain pathology together with psychometric limitations. These results highlight both commonalities and potential differences between OCD and hoarding disorder, and together with other lines of evidence, support the inclusion of the new disorder within the new Obsessive-Compulsive and Related Disorders chapter in DSM-5

Investigation of attentional bias in obsessive compulsive disorder with and without depression in visual search

Copyright: © 2013 Morein-Zamir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedWhether Obsessive Compulsive Disorder (OCD) is associated with an increased attentional bias to emotive stimuli remains controversial. Additionally, it is unclear whether comorbid depression modulates abnormal emotional processing in OCD. This study examined attentional bias to OC-relevant scenes using a visual search task. Controls, non-depressed and depressed OCD patients searched for their personally selected positive images amongst their negative distractors, and vice versa. Whilst the OCD groups were slower than healthy individuals in rating the images, there were no group differences in the magnitude of negative bias to concern-related scenes. A second experiment employing a common set of images replicated the results on an additional sample of OCD patients. Although there was a larger bias to negative OC-related images without pre-exposure overall, no group differences in attentional bias were observed. However, OCD patients subsequently rated the images more slowly and more negatively, again suggesting post-attentional processing abnormalities. The results argue against a robust attentional bias in OCD patients, regardless of their depression status and speak to generalized difficulties disengaging from negative valence stimuli. Rather, post-attentional processing abnormalities may account for differences in emotional processing in OCD.Peer reviewedFinal Published versio