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Author: Trevor W Robbins (395)


Feb
2018

To identify the white matter correlates of apathy and impulsivity in the major syndromes associated with frontotemporal lobar degeneration, using diffusion-weighted imaging and data from the PiPPIN (Pick's Disease and Progressive Supranuclear Palsy: Prevalence and Incidence) study. We included behavioral and language variants of frontotemporal dementia, corticobasal syndrome, and progressive supranuclear palsy.
Seventy patients and 30 controls underwent diffusion tensor imaging at 3-tesla after detailed assessment of apathy and impulsivity.

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Nov
2017

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.

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Feb
2018

Detecting causal relationships between actions and their outcomes is fundamental to guiding goal-directed behaviour. The ventromedial prefrontal cortex (vmPFC) has been extensively implicated in computing these environmental contingencies, via animal lesion models and human neuroimaging. However, whether the vmPFC is critical for contingency learning, and whether it can occur without subjective awareness of those contingencies, has not been established.

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Jan
2018

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.

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Jan
2018

Dysregulation of prefrontal cortical glutamatergic signalling via NMDA receptor hypofunction has been implicated in cognitive dysfunction and impaired inhibitory control in such neuropsychiatric disorders as schizophrenia, attention-deficit hyperactivity disorder and drug addiction. Although NMDA receptors functionally interact with metabotropic glutamate receptor 5 (mGluR5), the consequence of this interaction for glutamate release in the prefrontal cortex (PFC) remains unknown. We therefore investigated the effects of positive and negative allosteric mGluR5 modulation on changes in extracellular glutamate efflux in the medial PFC (mPFC) induced by systemic administration of the non-competitive NMDA receptor antagonist dizocilpine (or MK801) in rats.

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Nov
2017

The symptoms of obsessive-compulsive disorder (OCD) have been postulated to result from impaired executive functioning and excessive habit formation at the expense of goal-directed control and have been objectively demonstrated using neuropsychological tests in such patients. This study tested whether there is functional hypoactivation as well as dysconnectivity of discrete frontostriatal pathways during goal-directed planning in patients with OCD and in their unaffected first-degree relatives.
In total, 21 comorbidity-free patients with OCD, 19 clinically asymptomatic first-degree relatives of these patients, and 20 control participants were tested on a functional magnetic resonance optimized version of the Tower of London task.

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Jan
2018

Compulsions are repetitive, stereotyped thoughts and behaviors designed to reduce harm. Growing evidence suggests that the neurocognitive mechanisms mediating behavioral inhibition (motor inhibition, cognitive inflexibility) reversal learning and habit formation (shift from goal-directed to habitual responding) contribute toward compulsive activity in a broad range of disorders. In obsessive compulsive disorder, distributed network perturbation appears focused around the prefrontal cortex, caudate, putamen, and associated neuro-circuitry.

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Dec
2017

Impulsivity and reward expectancy are commonly interrelated. Waiting impulsivity, measured using the rodent 5-Choice Serial Reaction Time task, predicts compulsive cocaine seeking and sign (or cue) tracking. Here, we assess human waiting impulsivity using a novel translational task, the 4-Choice Serial Reaction Time task, and the relationship with reward cues.

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Oct
2017

Our daily lives involve high levels of repetition of activities within similar contexts. We buy the same foods from the same grocery store, cook with the same spices, and typically sit at the same place at the dinner table. However, when questioned about these routine activities, most of us barely remember the details of our actions.

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Oct
2017

Confidence and actions are normally tightly interwoven-if I am sure that it is going to rain, I will take an umbrella-therefore, it is difficult to understand their interplay. Stimulated by the ego-dystonic nature of obsessive-compulsive disorder (OCD), where compulsive actions are recognized as disproportionate, we hypothesized that action and confidence might be independently updated during learning. Participants completed a predictive-inference task designed to identify how action and confidence evolve in response to surprising changes in the environment.

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Sep
2017

Obsessive-Compulsive Disorder (OCD) is a common and highly debilitating psychiatric disorder. Amongst OCD sufferers are a significant number (40-60%) of so-called non-responders who do not fully respond to commonly available treatments, which include medications (Selective Serotonin Reuptake Inhibitors-SSRIs) and cognitive behavior therapy (CBT). Modern 'neuromodulatory' techniques such as Deep Brain Stimulation (DBS), repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS) potentially offer alternative forms of treatment for OCD patients who either do not respond to, or are unable or unwilling to take SSRIs and undergo CBT.

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Oct
2017

Impairments in attention and inhibitory control are endophenotypic markers of neuropsychiatric disorders such as schizophrenia and represent key targets for therapeutic management. Robust preclinical models and assays sensitive to clinically relevant treatments are crucial for improving cognitive enhancement strategies.
We assessed a rodent model with neural and behavioral features relevant to schizophrenia (gestational day 17 methylazoxymethanol acetate treatment (MAM-E17)) on a novel test of attention and executive function, and examined the impact of putative nootropic drugs.

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Jul
2017

The dopamine partial agonist aripiprazole is increasingly used to treat pathologies for which other antipsychotics are indicated because it displays fewer side effects, such as sedation and depression-like symptoms, than other dopamine receptor antagonists. Previously, we showed that aripiprazole may protect motivational function by preserving reinforcement-related signals used to sustain reward-maximization. However, the effect of aripiprazole on more cognitive facets of human reinforcement learning, such as learning from the forgone outcomes of alternative courses of action (i.

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Dec
1969

Economic games such as the Ultimatum Game (UG) and Prisoner's Dilemma (PD) are widely used paradigms for studying fairness and cooperation. Monetary versions of these games involve two players splitting an arbitrary sum of money. In real life, however, people's propensity to engage in cooperative behavior depends on their effort and contribution; factors that are well known to affect perceptions of fairness.

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Mar
2018

Excessive drinking to intoxication is the major behavioral characteristic of those addicted to alcohol but it is not the only one. Indeed, individuals addicted to alcohol also crave alcoholic beverages and spend time and put much effort into compulsively seeking alcohol, before eventually drinking large amounts. Unlike this excessive drinking, for which treatments exist, compulsive alcohol seeking is therefore another key feature of the persistence of alcohol addiction since it leads to relapse and for which there are few effective treatments.

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Sep
2017

Metabotropic glutamate receptor 4 (mGluR4) and dopamine Dreceptors are specifically expressed within the indirect pathway neurons of the striato-pallidal-subthalamic pathway. This unique expression profile suggests that mGluR4 and Dreceptors may play a cooperative role in the regulation and inhibitory control of behaviour. We investigated this possibility by testing the effects of a functionally-characterised positive allosteric mGluR4 modulator, 4-((E)-styryl)-pyrimidin-2-ylamine (Cpd11), both alone and in combination with the Dreceptor antagonist eticlopride, on two distinct forms of impulsivity.

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Jun
2017

Apathy and impulsivity are common and disabling consequences of frontotemporal lobar degeneration. They cause substantial carer distress, but their aetiology remains elusive. There are critical limitations to previous studies in this area including (i) the assessment of either apathy or impulsivity alone, despite their frequent co-existence; (ii) the assessment of behavioural changes within single diagnostic groups; and (iii) the use of limited sets of tasks or questions that relate to just one aspect of these multifactorial constructs.

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Dec
1969

Psychotic symptoms frequently occur in Parkinson's disease (PD), but their pathophysiology is poorly understood. According to the National Institute of Health RDoc programme, the pathophysiological basis of neuropsychiatric symptoms may be better understood in terms of dysfunction of underlying domains of neurocognition in a trans-diagnostic fashion. Abnormal cortico-striatal reward processing has been proposed as a key domain contributing to the pathogenesis of psychotic symptoms in schizophrenia.

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Dec
1969

The present study investigates human aversive Pavlovian-to-Instrumental Transfer (PIT) and possible influences of outcome devaluation and instrumental overtraining on this effect. PIT measures the extent to which a Pavlovian conditioned stimulus (CS) can increase instrumental responses independently paired with the same (outcome-specific transfer) or a different (general transfer) reinforcer. Two measures of PIT were obtained: the percentage of instrumental responses and the vigor of such responses.

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Apr
2017

To analyze the involvement of different brain regions in behavioral inhibition and impulsiveness, differences in activation were investigated in fMRI data from a response inhibition task, the stop-signal task, in 1709 participants. First, areas activated more in stop-success (SS) than stop-failure (SF) included the lateral orbitofrontal cortex (OFC) extending into the inferior frontal gyrus (ventrolateral prefrontal cortex, BA 47/12), and the dorsolateral prefrontal cortex (DLPFC). Second, the anterior cingulate and anterior insula (AI) were activated more on failure trials, specifically in SF versus SS.

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Aug
2017

Cognitive control has traditionally been associated with pFC based on observations of deficits in patients with frontal lesions. However, evidence from patients with Parkinson disease indicates that subcortical regions also contribute to control under certain conditions. We scanned 17 healthy volunteers while they performed a task-switching paradigm that previously dissociated performance deficits arising from frontal lesions in comparison with Parkinson disease, as a function of the abstraction of the rules that are switched.

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May
2017

Rats reared in social isolation exhibit various cognitive and behavioural abnormalities in adulthood. However, impulsivity following this treatment still remains unclear, especially in response to medications used in attention deficit hyperactivity disorder, such as amphetamine.
Using an isolation-rearing (IR) manipulation, the present study examined the effects of IR on impulsive action and impulsive choice when also treated with doses of D-amphetamine, by employing the five-choice serial reaction time task (5-CSRTT) and a temporal discounting of reward task (TDRT), respectively.

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Mar
2017

The ability to assign safety to stimuli in the environment is integral to everyday functioning. A key brain region for this evaluation is the ventromedial prefrontal cortex (vmPFC). To investigate the importance of vmPFC safety signaling, we used neuroimaging of Pavlovian fear reversal, a paradigm that involves flexible updating when the contingencies for a threatening (CS+) and safe (CS-) stimulus reverse, in a prototypical disorder of inflexible behavior influenced by anxiety, Obsessive Compulsive Disorder (OCD).

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Dec
1969

Variations in genes encoding several GABAreceptors have been associated with human drug and alcohol abuse. Among these, a number of human studies have suggested an association between, the gene encoding GABAreceptor β1 subunits, with Alcohol dependence (AD), both on its own and comorbid with other substance dependence and psychiatric illnesses. In the present study, we hypothesized that thegenetically-associated increased risk for developing alcoholism may be associated with impaired behavioral control and altered sensitivity to reward, as a consequence of altered brain function.

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May
2017

Impairments in behavioral flexibility lie at the core of anxiety and obsessive-compulsive disorders. Few studies, however, have investigated the neural substrates of natural variation in behavioral flexibility and whether inflexible behavior is linked to anxiety and peripheral markers of stress and monoamine function.
The objective of the study was to investigate peripheral and central markers associated with perseverative behavior on a spatial-discrimination serial reversal learning task.

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Jan
2018

Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects.

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Feb
2017

Novelty-seeking tendencies in adolescents may promote innovation as well as problematic impulsive behaviour, including drug abuse. Previous research has not clarified whether neural hyper- or hypo-responsiveness to anticipated rewards promotes vulnerability in these individuals. Here we use a longitudinal design to track 144 novelty-seeking adolescents at age 14 and 16 to determine whether neural activity in response to anticipated rewards predicts problematic drug use.

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Dec
1969

The ability to make decisions and act quickly without hesitation can be advantageous in many settings. However, when persistently expressed, impulsive decisions and actions are considered risky, maladaptive and symptomatic of such diverse brain disorders as attention-deficit hyperactivity disorder, drug addiction and affective disorders. Over the past decade, rapid progress has been made in the identification of discrete neural networks that underlie different forms of impulsivity - from impaired response inhibition and risky decision making to a profound intolerance of delayed rewards.

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Jun
2017

Serotonin has been implicated in promoting self-control, regulation of hunger and physiological homeostasis, and regulation of caloric intake. However, it remains unclear whether the effects of serotonin on caloric intake reflect purely homeostatic mechanisms, or whether serotonin also modulates cognitive processes involved in dietary decision making. We investigated the effects of an acute dose of the serotonin reuptake inhibitor citalopram on choices between food items that differed along taste and health attributes, compared with placebo and the noradrenaline reuptake inhibitor atomoxetine.

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Apr
2017

Evidence suggests that disturbances in neurobiological mechanisms of reward and inhibitory control maintain addiction and provoke relapse during abstinence. Abnormalities within the dopamine system may contribute to these disturbances and pharmacologically targeting the D3 dopamine receptor (DRD3) is therefore of significant clinical interest. We used functional magnetic resonance imaging to investigate the acute effects of the DRD3 antagonist GSK598809 on anticipatory reward processing, using the monetary incentive delay task (MIDT), and response inhibition using the Go/No-Go task (GNGT).

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Jan
2017

Schizophrenia is a complex and debilitating illness with strong genetic loading. In line with its heterogeneous symptomatology, evidence suggests genetic etiologies for the phenotypes in schizophrenia. A search across endophenotypes has pointed towards consistent findings in its neurocognitive deficits.

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Nov
2016

The traditional view that mental disorders are distinct, categorical disorders has been challenged by evidence that disorders are highly comorbid and exist on a continuum (e.g., Caspi et al.

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Nov
2016

Despite calls for integration of neurobiological methods into research on youth resilience (high competence despite high adversity), we know little about structural brain correlates of resilient functioning. The aim of the current study was to test for brain regions uniquely associated with positive functioning in the context of adversity, using detailed phenotypic classification.
1,870 European adolescents (M = 14.

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Apr
2017

A recent hypothesis has suggested that core deficits in goal-directed behavior in obsessive-compulsive disorder (OCD) are caused by impaired frontostriatal function. We tested this hypothesis in OCD patients and control subjects by relating measures of goal-directed planning and cognitive flexibility to underlying resting-state functional connectivity.
Multiecho resting-state acquisition, combined with micromovement correction by blood oxygen level-dependent sensitive independent component analysis, was used to obtain in vivo measures of functional connectivity in 44 OCD patients and 43 healthy comparison subjects.

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Dec
1969

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.
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.

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Dec
1969

Negative life events (NLE) contribute to anxiety and depression disorders, but their relationship with brain functioning in adolescence has rarely been studied. We hypothesized that neural response to social threat would relate to NLE in the frontal-limbic emotional regions. Participants (N = 685) were drawn from the Imagen database of 14-year-old community adolescents recruited in schools.

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Dec
1969

The origins and rationale of the Cambridge Neuropsychological Test Automated Battery (CANTAB) as a cross-species translational instrument suitable for use in human neuropsychopharmacological studies are reviewed. We focus on its use for the early assessment and detection of Alzheimer's disease, in particular the Paired Associates Learning (PAL) test. We consider its psychometric properties, neural validation, and utility, including studies on large samples of healthy volunteers, patients with mild cognitive impairment (MCI), and Alzheimer's disease.

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Nov
2017

There is a concerted research effort to investigate brain mechanisms underlying addiction processes that may predicate the development of new compounds for treating addiction. One target is the brain's opioid system, because of its role in the reinforcing effects of substances of abuse. Substance-dependent populations have increased numbers of the mu opioid receptor (MOR) in fronto-striatal regions that predict drug relapse, and demonstrate disturbances in these regions during the processing of non-drug rewards.

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Dec
1969

Some patients suffering from the same neuropsychiatric disorder may have no overlapping symptoms whilst others may share symptoms common to other distinct disorders. Therefore, the Research Domain Criteria initiative recognises the need for better characterisation of the individual symptoms on which to focus symptom-based treatment strategies. Many of the disorders involve dysfunction within the prefrontal cortex (PFC) and so the marmoset, due to their highly developed PFC and small size, is an ideal species for studying the neurobiological basis of the behavioural dimensions that underlie these symptoms.

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Oct
2016

Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC).
We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a Dreceptor agonist and on D1 receptor binding and DA content in the PFC and striatum.

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Oct
2016

A chromosomal microdeletion at the 22q11.2 locus is associated with extensive cognitive impairments, schizophrenia and other psychopathology in humans. Previous reports indicate that mouse models of the 22q11.

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Dec
1969

Parkinson's disease impairs the inhibition of responses, and whilst impulsivity is mild for some patients, severe impulse control disorders affect ∼10% of cases. Based on preclinical models we proposed that noradrenergic denervation contributes to the impairment of response inhibition, via changes in the prefrontal cortex and its subcortical connections. Previous work in Parkinson's disease found that the selective noradrenaline reuptake inhibitor atomoxetine could improve response inhibition, gambling decisions and reflection impulsivity.

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Jun
2016

Cocaine addiction is a major public health problem that is particularly difficult to treat. Without medically proven pharmacological treatments, interventions to change the maladaptive behavior of addicted individuals mainly rely on psychosocial approaches. Here we report on impairments in cocaine-addicted patients to act purposefully toward a given goal and on the influence of extended training on their behavior.

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