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

Elevated levels of hoarding in ADHD: A special link with inattention.

Hoarding Disorder (HD) is under recognised and under-treated. Though HD develops by early adulthood, patients present only later in life, resulting in research based largely on samples of predominantly older females. Whilst formerly associated with Obsessive-Compulsive Disorder (OCD), it is now recognised that individuals with HD often have inattention symptoms reminiscent of Attention Deficit/Hyperactivity Disorder (ADHD). Here, we investigated HD in adults with ADHD. Patients in an ADHD clinic (n = 88) reported on ADHD, HD and OCD-related symptoms, and compared with age, gender and education matched controls (n = 90). Findings were assessed independently in an online UK sample to verify replication using a dimensional approach (n = 220). Clinically significant hoarding symptoms were found in ∼20% versus 2% of ADHD and control groups, respectively, with those with hoarding being on average in their thirties and with approximately half being male. Greater hoarding severity was noted even in the remaining patients compared with controls (d = 0.89). Inattention was the only significant statistical predictor of hoarding severity in patients. Similarly, inattention, alongside depression and anxiety were the greatest predictors of hoarding in the independent sample where 3.2% identified as having clinically significant hoarding. Patients with ADHD had a high frequency of hoarding symptoms, which were specifically linked to inattention. HD should be routinely assessed in individuals with ADHD, as they do not typically disclose associated difficulties, despite these potentially leading to impaired everyday functioning. Research in HD should also investigate adults with ADHD, who are younger and with a greater prevalence of males than typical HD samples

Avoid jumping to conclusions under uncertainty in Obsessive Compulsive Disorder.

High levels of intolerance of uncertainty (IU) could contribute to abnormal decision making in uncertain situations. Patients with Obsessive Compulsive Disorder (OCD) often report high IU, indecisiveness and the need to seek greater certainty before making decisions. The Beads task is a commonly used task assessing the degree of information gathering prior to making a decision and so would be predicted to show impairments in OCD patients. Results to date have found mixed support for this, possibility due to methodological issues. Here, a group of OCD patients (n = 50) with no comorbidities was compared with age, gender, and verbal-IQ matched controls (n = 50) on the most commonly used version of the Beads task. An independent sample of healthy volunteers with high versus low OC symptoms, and high versus low IU were also assessed (n = 125). There was no evidence that patients with OCD differed from control volunteers in the degree of information gathering prior to making a decision. Medication status and age did not appear to mediate performance. Similarly, there were no association in healthy volunteers between task performance and OC or IU characteristics. Additional measures examining the degree of certainty initially showed support for greater uncertainty in patients, but this was due to deviations from task instructions in a subset of patients. We conclude that despite the large sample size and good matching between groups, the Beads task in its most widely used form is not a useful measure of IU or of information gathering in OCD. The results argue against a robust behavioural difference in OCD when compared to controls. Recommendations for future studies employing the task are discussed

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)

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 analyse 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

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