Action-sequence learning, habits and automaticity in obsessive-compulsive disorder

Enhanced habit formation, greater automaticity and impaired goal/habit arbitration in obsessive-compulsive disorder (OCD) are key hypotheses from the goal/habit imbalance theory of compulsion which have not been directly investigated. This article tests these hypotheses using a combination of newly developed behavioral tasks. First, we trained patients with OCD and healthy controls, using a novel smartphone app, to perform chunked action sequences, previously shown to engage habit brain circuitry. The motor training was daily over one month period. There was equivalent procedural learning and attainment of habitual performance (measured with an objective criteria of automaticity) in both groups, despite greater subjective habitual tendencies in patients with OCD, self-reported via a recently developed questionnaire. We then used a combination of follow-up behavioral tasks to further assess the arbitration between previous automatic and new goal-directed action sequences. We found no evidence for impairments of goal/habit arbitration in OCD following re-evaluation based on monetary feedback, although there was a greater preference for engaging in the trained habitual sequence under certain conditions which may have derived from its intrinsic value. These findings may lead to a reformulation of the goal/habit imbalance hypothesis in OCD. Finally, OCD patients with higher compulsivity scores and habitual tendencies showed more engagement with the motor habit-training app and reported symptom alleviation, with implications for its potential use as a form of habit reversal therapy

Impulsivity in abstinent alcohol and polydrug dependence: a multidimensional approach.

RATIONALE: Dependence on drugs and alcohol is associated with impaired impulse control, but deficits are rarely compared across individuals dependent on different substances using several measures within a single study. OBJECTIVES: We investigated impulsivity in abstinent substance-dependent individuals (AbD) using three complementary techniques: self-report, neuropsychological and neuroimaging. We hypothesised that AbDs would show increased impulsivity across modalities, and that this would depend on length of abstinence. METHODS: Data were collected from the ICCAM study: 57 control and 86 AbDs, comprising a group with a history of dependence on alcohol only (n = 27) and a group with history of dependence on multiple substances ("polydrug", n = 59). All participants completed self-report measures of impulsivity: Barratt Impulsiveness Scale, UPPS Impulsive Behaviour Scale, Behaviour Inhibition/Activation System and Obsessive-Compulsive Inventory. They also performed three behavioural tasks: Stop Signal, Intra-Extra Dimensional Set-Shift and Kirby Delay Discounting; and completed a Go/NoGo task during fMRI. RESULTS: AbDs scored significantly higher than controls on self-report measures, but alcohol and polydrug dependent groups did not differ significantly from each other. Polydrug participants had significantly higher discounting scores than both controls and alcohol participants. There were no group differences on the other behavioural measures or on the fMRI measure. CONCLUSIONS: The results suggest that the current set of self-report measures of impulsivity is more sensitive in abstinent individuals than the behavioural or fMRI measures of neuronal activity. This highlights the importance of developing behavioural measures to assess different, more relevant, aspects of impulsivity alongside corresponding cognitive challenges for fMRI.This article presents independent research funded by the Medical Research Council as part of their addiction initiative (grant number G1000018). GSK kindly funded the functional and structural MRI scans that took place at Imperial College. The research was carried out at the NIHR/Wellcome Trust Imperial Clinical Research Facility, the NIHR/Wellcome Trust Cambridge Research Facility and Clinical Trials Unit at Salford Royal NHS Foundation Trust, and is supported by the North West London, Eastern and Greater Manchester NIHR Clinical Research Networks.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s00213-016-4245-

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description.

OBJECTIVES: We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction - reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants. EXPERIMENTAL DESIGN: Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity. A coordinate-based activation likelihood estimation (ALE) meta-analysis was carried out for the reward and impulsivity tasks to help establish region of interest (ROI) placement. A group of healthy participants was recruited from across three centres (total n=43) to investigate inter-centre differences. Principle observations: The pattern of response observed for each of the three tasks was consistent with previous studies using similar paradigms. At the whole brain level, significant differences were not observed between centres for any task. CONCLUSIONS: In developing this platform we successfully integrated neuroimaging data from three centres, adapted validated tasks and applied whole brain and ROI approaches to explore and demonstrate their consistency across centres.Medical Research Council (Grant ID: G1000018), GlaxoSmithKlineThis is the author accepted manuscript. The final version is available from SAGE Publications via http://dx.doi.org/10.1177/026988111666859

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Dopamine, Cognitive Flexibility and IQ: Epistatic COMT:DRD2 Gene-Gene Interactions Modulate Mental Rigidity

Cognitive flexibility has been hypothesized to be neurochemically rooted in dopamine neurotransmission. Nonetheless, underpowered sample sizes and contradictory meta-analytic findings have obscured the role of dopamine genes in cognitive flexibility and neglected potential gene-gene interactions. In this largest neurocognitive-genetic study to date (N=1400), single nucleotide polymorphisms associated with elevated prefrontal dopamine levels (Catechol-O-MethylTransferase, COMT; rs4680) and diminished striatal dopamine (C957T; rs6277) were both implicated in Wisconsin Card Sorting Test performance. Crucially, however, these genetic effects were only evident in low-IQ participants, suggesting high intelligence compensates for, and eliminates, the effect of dispositional dopamine functioning on flexibility. This interaction between cognitive systems may explain and resolve previous empirical inconsistencies in highly educated participant samples. Moreover, compensatory gene-gene interactions were discovered between COMT and DRD2, such that genotypes conferring either elevated prefrontal dopamine or diminished striatal dopamine – via heightened striatally-concentrated D2 dopamine receptor availability – are sufficient for cognitive flexibility, but neither is necessary. The study has therefore revealed a form of epistatic redundancy or substitutability amongst dopamine systems in shaping adaptable thought and action, thus defining boundary conditions for dopaminergic effects on flexible behavior. These results inform theories of clinical disorders and psychopharmacological interventions and uncover complex fronto-striatal synergies in human flexible cognition

Cognitive Rigidity, Habitual Tendencies, and Obsessive-Compulsive Symptoms: Individual Differences and Compensatory Interactions

Recent theories have posited a range of cognitive risk factors for obsessive-compulsive disorder (OCD), including cognitive inflexibility and a maladaptive reliance on habits. However, empirical and methodological inconsistencies have obscured the understanding of whether inflexibility and habitual tendencies indeed shape OCD symptoms in clinical and sub-clinical populations, and whether there are notable interactions amongst these traits. The present investigation adopted an interactionist individual differences approach to examine the associations between behaviourally-assessed cognitive flexibility and subclinical OCD symptomatology. It also explored the nature of the interactions between cognitive flexibility and habitual tendencies, and the degree to which these cognitive traits predict subclinical OCD symptomatology. Across two studies, including a preregistration, Bayesian and regression analyses revealed that cognitive inflexibility and compulsive habitual tendencies act as unique and independent predictors of subclinical OCD symptomatology. Furthermore, there was a significant interaction between cognitive rigidity and habitual compulsivity, which accounted for 49.4% of the variance in subclinical OCD symptomatology in Study 1, and 37.3% in Study 2. In-depth analyses revealed a compensatory effect between cognitive inflexibility and habitual compulsivity such that both are necessary for OCD symptomatology, but neither is sufficient. These results imply that in order to generate reliable and nuanced models of the endophenotype of OCD symptomatology, it is essential to account for interactions between psychological traits. Moreover, the present findings have important implications for theories on the cognitive roots of OCD, and potentially in the development of interventions that target both cognitive inflexibility and habitual compulsivity

Harnessing temperament to elucidate the complexities of serotonin function

This review highlights the utility of using concepts of consistent behavioural patterns (CBPs) (temperament in healthy individuals; and psychopathology of mental illness) in conjunction with situational contextuality. We also point to multiple roles of central serotonin (5-hydroxytryptamine, 5-HT) as a biomarker of CBPs. We use empirical demonstrations of the complex and trait-dependent effects of manipulating 5-HT via acute dietary tryptophan depletion (ATD) to highlight the relevance of these constructs in the neurochemical control of behaviour. Neurochemical and temperament trait interactions, for example, 5-HT and empathy, psychopathy, neuroticism, impulsivity, and hyperthymia are postulated to underlie this complexity

Cognitive flexibility: neurobehavioural correlates of changing one's mind

Behavioural and cognitive flexibility allow adaptation to a changing environment. Most tasks used to investigate flexibility require switching reactively in response to deterministic task-response rules. In daily life, flexibility often involves a volitional decision to change behaviour. This can be instigated by environmental signals, but these are frequently unreliable. We report results from a novel ‘change your mind’ task, which assesses volitional switching under uncertainty, without the need for rule-based learning. Participants completed a two-alternative choice task and following spurious feedback, were presented with the same stimulus again. Subjects had the opportunity to repeat or change their response. Forty healthy participants completed the task whilst undergoing a functional MRI scan. Participants predominantly repeated their choice but changed more when their first response was incorrect or when feedback was negative. Greater activations for changing were found in the inferior frontal junction, anterior insula, anterior cingulate and dorsolateral prefrontal cortex. Changing responses were also accompanied by reduced connectivity from the anterior insula and orbitofrontal cortices to the occipital cortex. Using multivariate pattern analysis of brain activity, we predicted with 77% reliability whether participants would change their mind. These findings extend our understanding of cognitive flexibility in daily life by assessing volitional decision-making.</p