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Trevor W Robbins

Publications and source records attributed to Trevor W Robbins.

At least 37 records · Page 2Linked to original sources
PubMed2006

Neuropharmacological modulation of cognition.

PURPOSE OF REVIEW: Problems relating to impulsivity, attention, and working memory occur in many neuropsychiatric disorders and represent important targets for pharmacological intervention. The purpose of this article is to review recent neuropharmacological manipulation studies in humans relating to these domains. RECENT FINDINGS: Serotonin manipulations in healthy volunteers did not affect response inhibition, a cognitive function implicated in impulsive symptoms of attention deficit hyperactivity disorder, trichotillomania, and substance abuse. Serotonin manipulations did affect performance on cognitive tests involving emotionally salient rewards and feedback, suggesting involvement of this neurochemical in affective aspects of impulsivity. Attentional deficits in attention deficit hyperactivity disorder and visuospatial neglect were ameliorated by noradrenergic drugs. Noradrenergic beta-blockade suppressed the encoding of emotionally arousing unpleasant stimuli and reduced amygdala activation in healthy volunteers, with potential implications for posttraumatic stress disorder. Dopaminergic manipulations affected aspects of working memory in healthy volunteers and in patients with Parkinson's disease, with evidence for bidirectional effects depending on baseline performance. SUMMARY: Recent findings raise exciting prospects for modulating impulsivity, attention, and working memory in a variety of neuropsychiatric disorders. Future studies should use computerized cognitive assessment, measures of functional genetic polymorphisms, and neuroimaging techniques, in order to further elucidate the neurochemical substrates of cognition and optimize treatment approaches.

Attention↗
PubMed2006

Selective excitotoxic lesions of the hippocampus and basolateral amygdala have dissociable effects on appetitive cue and place conditioning based on path integration in a novel Y-maze procedure.

The hippocampus and amygdala are thought to be functionally distinct components of different learning and memory systems. This functional dissociation has been particularly apparent in pavlovian fear conditioning, where the integrity of the hippocampus is necessary for contextual conditioning, and of the amygdala for discrete cue conditioning. Their respective roles in appetitive conditioning, however, remain equivocal mainly due to the lack of agreement concerning the operational definition of a 'context'. The present study used a novel procedure to measure appetitive conditioning to spatial context or to a discrete cue. Following selective excitotoxic lesions of the hippocampus (HPC) or basolateral amygdala (BLA), rats were initially trained to acquire discrete CS-sucrose conditioning in a Y-maze apparatus with three topographically identical chambers, the chambers discriminated only on the basis of path integration. The same group of animals then underwent 'place/contextual conditioning' where the CS presented in a chamber assigned as the positive chamber was paired with sucrose, but the same CS presented in either of the other two chambers was not. Thus, spatial context was the only cue that the animal could use to retrieve the value of the CS. HPC lesions impaired the acquisition of conditioned place preference but facilitated the acquisition of cue conditioning, while BLA lesions had the opposite effect, retarding the acquisition of cue conditioning but leaving the acquisition of conditioned place preference intact. Here we provide strong support for the notion that the HPC and BLA subserve complementary and competing roles in appetitive cue and contextual conditioning.

Amygdala↗
PubMed2006

Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania.

OBJECTIVE: Problems with inhibiting certain pathological behaviors are integral to obsessive-compulsive disorder (OCD), trichotillomania, and other putative obsessive-compulsive spectrum disorders. The authors assessed and compared motor inhibition and cognitive flexibility in OCD and trichotillomania for the first time, to their knowledge. METHOD: The Stop-Signal Task and the Intradimensiona/Extradimensional Shift Task were administered to 20 patients with OCD, 17 patients with trichotillomania, and 20 healthy comparison subjects. RESULTS: Both OCD and trichotillomania showed impaired inhibition of motor responses. For trichotillomania, the deficit was worse than for OCD, and the degree of the deficit correlated significantly with symptom severity. Only patients with OCD showed deficits in cognitive flexibility. CONCLUSIONS: Impaired inhibition of motor responses (impulsivity) was found in OCD and trichotillomania, whereas cognitive inflexibility (thought to contribute to compulsivity) was limited to OCD. This assessment will advance the characterization and classification of obsessive-compulsive spectrum disorders and aid the development of novel treatments.

Adult↗
PubMed2005

Chemistry of the mind: neurochemical modulation of prefrontal cortical function.

The neurochemical modulation of prefrontal cortical function is reviewed with special reference to the ascending dopaminergic and serotoninergic projections. Evidence is surveyed from studies of rats, nonhuman primates, and humans to suggest that prefrontal dopamine has specific functions in attentional control and working memory, mediated mainly through the D1 receptor, whereas manipulations of serotonin are shown by contrast to affect reversal learning in monkeys and human volunteers and measures of impulsivity in rats. These findings are discussed in the context of these as well as other neurotransmitter systems (including noradrenaline and acetylcholine) having distinct roles in the neuromodulation of prefrontal cortical function. The capacity of the prefrontal cortex itself to exert top-down regulation of these ascending neurochemical systems is also discussed.

Animals↗
PubMed2005

Lack of effects of guanfacine on executive and memory functions in healthy male volunteers.

RATIONALE: Guanfacine is an alpha2-adrenergic receptor agonist that has been shown to have beneficial effects on working memory and attentional functions in monkeys and in patients with attention deficit hyperactivity disorder. OBJECTIVES: The aim of this study was to further investigate the cognitive-enhancing properties of guanfacine using an established battery of tasks measuring executive and memory functions. METHODS: Sixty healthy male volunteers were randomised into three groups. Cognitive testing was performed from +2 to +4 h after double-blind administration of a single oral dose of 1 or 2 mg of guanfacine or placebo. RESULTS: Systolic blood pressure was significantly reduced by both doses of guanfacine at the end of the testing session. There were no statistically significant effects on any of the cognitive measures. Two trend effects were observed with poorer performance on digit span backward and slower 'Go' reaction times after guanfacine. CONCLUSION: This study found no improvement of prefrontal memory or executive functions after guanfacine. Negative effects on blood pressure and trend effects on digit span backward and go reaction time indicate a mild sedative effect of guanfacine at these doses, possibly via mechanisms of autoreceptor down-regulation.

Adult↗
PubMed2005

Attentional and motivational deficits in rats withdrawn from intravenous self-administration of cocaine or heroin.

RATIONALE: Identifying the long-term neurocognitive sequelae of drug addiction may have important implications for understanding the compulsive, chronically relapsing nature of this brain disorder. OBJECTIVES: Our aim was to investigate the consequences of chronic intravenous self-administration of cocaine or heroin on visual attentional processes in rats. METHODS: Adult male rats were pretrained on a five-choice serial reaction time task (5-CSRTT) of sustained visual attention and impulsivity and later trained to self-administer cocaine or heroin intravenously during multiple 'long-access' self-administration cycles. Control rats had identical training and surgical experience, but received passive infusions of saline during self-administration sessions. Executive cognitive processes of selection and inhibitory response control were evaluated 24 h after drug discontinuation and for a further 6 days prior to the next cycle of self-administration. RESULTS: Findings indicate similar behavioural disturbances on the five-choice task in cocaine- and heroin-withdrawn rats with significantly impaired attentional accuracy, increased omissions and slower latencies to respond correctly during the early, but not late, withdrawal period. The self-administration of either drug was not associated with significant alterations in impulsive actions, and there was no evidence of persistent alterations in visual attentional performance. However, unlike rats self-administering cocaine, the motivation to collect food reward on the 5-CSRTT was significantly reduced in heroin-withdrawn animals for a period of at least 6 weeks. CONCLUSIONS: These data, together with recent findings of attentional dysfunction during the withdrawal of intravenous self-administration of amphetamine, suggest that generically different drugs of abuse produce similar disturbances in visual attentional performance during the early withdrawal period.

Analgesics↗
PubMed2005

Strategy implementation in obsessive-compulsive disorder and trichotillomania.

BACKGROUND: The use of strategies to aid performance when undertaking neuropsychological tasks is dependent on intact fronto-striatal circuitry, and growing evidence suggests impaired spontaneous use of strategies in patients with obsessive-compulsive disorder (OCD). However, studies to date have not examined the effects of strategy training on task performance in OCD or in trichotillomania (compulsive hair-pulling, a condition that has been argued to share overlap with OCD in terms of phenomenology and co-morbidity). METHOD: The ability to generate novel visuospatial sequences using a computer interface was examined before and after undertaking optimal strategy training in 20 OCD patients, 17 trichotillomania patients, and 20 controls (matched for age, education, and IQ). RESULTS: OCD patients failed to improve ability to generate novel sequences above baseline despite successfully completing strategy training to the same extent as other groups. In contrast, performance of trichotillomania patients improved significantly after training to the same extent as controls. Groups did not differ on memory span, trial-by-trial action monitoring, or ability to generate novel visuospatial sequences prior to strategy training. CONCLUSIONS: Strategy implementation deficits, suggestive of cognitive inflexibility and fronto-striatal dysfunction, appear integral to the neurocognitive profile of OCD but not trichotillomania. Future research should investigate cognitive flexibility in obsessive-compulsive spectrum disorders using a variety of paradigms, and clarify the contribution of specific neural structures and transmitter systems to deficits reported.

Adult↗
PubMed2005

A comparison of multiple 5-HT receptors in two tasks measuring impulsivity.

Impulsivity has often been assumed to be a unitary construct. However dissociable forms of impulsive behaviour may exist, each with distinct neurochemical underpinnings. To test this hypothesis, behavioural effects of three partially selective serotonergic (5-HT) ligands, ketanserin (5-HT2(A, C) receptor antagonist), SER-082 (5-HT2(C, B) receptor antagonist) and SB-270146-A (5-HT6 receptor antagonist) were compared in two tests of impulsivity. The five-choice serial reaction time task (5-csrtt) and a delayed reward task were chosen as they measure theoretically different types of impulsivity, behavioural inhibition versus choice preference for a delayed reward. Dissociation was seen between the effects of ketanserin, which decreased impulsivity in the 5-csrtt, but had no effect on the delayed reward task, and SER-082, which had no effect on the 5-csrtt, but decreased impulsive responding in the delayed reward task. SB-270146-A had no effect in either paradigm. The results suggest that the 5-csrtt and the delayed reward task do in fact measure different types of impulsive behaviour, which are at least partially neurochemically distinct.

Animals↗
PubMed2005

Individual differences in threat sensitivity predict serotonergic modulation of amygdala response to fearful faces.

RATIONALE: In this study we used functional magnetic resonance imaging (fMRI) to examine the effects of acute tryptophan depletion (ATD), a well-recognised method for inducing transient cerebral serotonin depletion, on brain activation to fearful faces. OBJECTIVES: We predicted that ATD would increase the responsiveness of the amygdala to fearful faces as a function of individual variation in threat sensitivity. METHODS: Twelve healthy male volunteers received a tryptophan depleting drink or a tryptophan balancing amino acid drink (placebo) in a double-blind crossover design. Five hours after drink ingestion participants were scanned whilst viewing fearful, happy and neutral faces. RESULTS: Consistent with previous findings, fearful faces induced significant signal change in the bilateral amygdala/hippocampus as well as the fusiform face area and the right dorsolateral prefrontal cortex. Furthermore, ATD modulated amygdala/hippocampus activation in response to fearful relative to happy faces as a function of self-reported threat sensitivity (as measured with the Behavioral Inhibition Scale; Carver CS, White TL (1994) Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J Pers Soc Psychol 67:319-333). CONCLUSION: The data support the hypothesis that individual variation in threat sensitivity interacts with manipulation of 5-HT function to bias the processing of amygdala-dependent threat-relevant stimuli.

Adolescent↗
PubMed2005

Distinguishing separable domains of cognition in human and animal studies: what separations are optimal for targeting interventions? A summary of recommendations from breakout group 2 at the measurement and treatment research to improve cognition in schizophrenia new approaches conference.

At the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) New Approaches Conference, a discussion group focused on directions for future research that are critical to enhancing our understanding of the distinctions among key cognitive domains that have relevance for the development of cognition-enhancing interventions. One set of recommendations emphasizes the need for examining and optimizing the psychometric properties of relevant measurement paradigms from cognitive psychology and cognitive neuroscience. This step is critical to translating many notable advances in these basic fields into measures that would be appropriate for clinical trials. A second set of recommendations focuses on key directions for the development and application of animal models of cognitive processes that would greatly aid the discovery and preclinical testing of potential cognition-enhancing agents. As part of this process, the group noted several existing animal paradigms that have particular promise as measures in the key cognitive domains in schizophrenia identified by the MATRICS Neurocognition Committee.

Animals↗
PubMed2005

Synthesizing schizophrenia: a bottom-up, symptomatic approach.

The cognitive deficits in schizophrenia are discussed in terms of the other symptoms of the disorder, as well as according to a translational approach that involves using similar or analogous tests for humans and experimental animals. This approach, it is argued, will enable the testing of novel drugs and the development of adequate etiological models of schizophrenia.

Attention↗
PubMed2005

Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens.

Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However, an important but unresolved issue is whether this forebrain structure also contributes to the consolidation of fundamental forms of appetitive learning acquired by Pavlovian associative processes. In addition, although dopaminergic and glutamatergic influences in the NAc have been implicated in instrumental learning, it is unclear whether similar mechanisms operate during Pavlovian conditioning. To evaluate these issues, the effects of posttraining intra-NAc infusions of D1, D2, and NMDA receptor antagonists, as well as d-amphetamine, were determined on Pavlovian autoshaping in rats, which assesses learning by discriminated approach behavior to a visual conditioned stimulus predictive of food reward. Intracerebral infusions were given either immediately after each conditioning session to disrupt early memory consolidation or after a delay of 24 h. Findings indicate that immediate, but not delayed, infusions of both D1 (SCH 23390) and NMDA (AP-5) receptor antagonists significantly impair learning on this task. By contrast, amphetamine and the D2 receptor antagonist sulpiride were without significant effect. These findings provide the most direct demonstration to date that D1 and NMDA receptors in the NAc contribute to, and are necessary for, the early consolidation of appetitive Pavlovian learning.

Animals↗
PubMed2005

Double dissociation between serotonergic and dopaminergic modulation of medial prefrontal and orbitofrontal cortex during a test of impulsive choice.

Dysregulation of the prefrontal cortex (PFC) has been implicated in impulse control disorders, including attention deficit hyperactivity disorder. A growing body of evidence suggests that impulsivity is non-unitary in nature, and recent data indicate that the ventral and dorsal regions of the PFC are differentially involved in distinct aspects of impulsive behaviour, findings which may reflect differences in the monoaminergic regulation of these regions. In the current experiment, levels of dopamine, serotonin and their metabolites were measured in the medial PFC (n = 12) and orbitofrontal cortex (OFC) (n = 19) of rats using in vivo microdialysis during the delay-discounting model of impulsive choice, where impulsivity is defined as selection of small immediate over larger delayed rewards. Yoked groups were also dialysed to control for instrumental responding and reward delivery. Significant increases in 5-hydroxytryptamine efflux were observed in the mPFC, but not in the OFC, during task performance but not under yoked control conditions. In the OFC, 3,4-di-hydroxy-phenylocetic acid (DOPAC) levels increased in animals performing the task but not in yoked animals, whereas mPFC DOPAC levels increased in all subjects. These data suggest a double dissociation between serotonergic and dopaminergic modulation of impulsive decision-making within distinct areas of frontal cortex.

Animals↗
PubMed2005

The BDNF Val66Met polymorphism has a gender specific influence on planning ability in Parkinson's disease.

Parkinson's disease (PD) patients show a range of cognitive deficits,which may relate to abnormalities in dopaminergic transmission in fronto-striatal circuitry. In this study, we have investigated the impact of brainderived neurotrophic factor (BDNF) val66met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. This polymorphism significantly influences BDNF secretion in the CNS, and BDNF is known to influence dopaminergic neurons and cognitive processes. Patients with PD totalling 291 who had undergone detailed motor and cognitive assessments as part of a population-based study of PD were genotyped for the BDNF val66met polymorphism. The impact of this polymorphism on cognitive ability was determined using multivariate analysis to adjust for possible confounding variables. Patients with low rates of BDNF secretion (met alleles) performed significantly better at the TOL task than those with high rates of secretion (val alleles). Furthermore, subgroup analyses revealed that the effect is most apparent in women and among patients with prior dopaminergic exposure. We speculate that BDNF may interact with dopaminergic transmission and dopamine receptor stimulation in the frontostriatal circuitry, with subsequent consequences on cognition in Parkinson's disease.

Aged↗
PubMed2005

Local glutamate receptor antagonism in the rat prefrontal cortex disrupts response inhibition in a visuospatial attentional task.

RATIONALE: Converging evidence implicates discrete areas of the rat prefrontal cortex in the modulation of different aspects of attention and executive control. Furthermore, the pharmacology of these behaviours has been relatively well characterised for the monoamine systems in a task of visuospatial attention, but it is not known how glutamate receptor antagonism in discrete regions of the prefrontal cortex affects attentional performance. OBJECTIVES: To investigate the role of N-methyl-D-aspartate (NMDA) receptor antagonism in the prelimbic and infralimbic cortices (within the same animals) on performance of the five-choice serial reaction time task (5CSRTT), which assesses visuospatial attention and response inhibition. METHODS: Following training on the 5CSRTT, rats were implanted with bilateral guide cannulae aimed at the medial prefrontal cortex (mPFC). Rats received micro infusions of the competitive NMDA receptor antagonist 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid [(R)-CPP; dissolved in saline to give 10 ng and 50 ng per side] into the prelimbic cortex, then three more infusions (saline, 10 ng and 50 ng per side) into the infralimbic cortex, in a counterbalanced design. They were then tested on a version of the task identical to that used in training. RESULTS: (R)-CPP microinfusions impaired accuracy and increased omissions across both cortical regions. (R)-CPP microinfusions robustly increased premature responding only when infused into the infralimbic, but not prelimbic, cortex. CONCLUSIONS: These results indicate that NMDA receptor neurotransmission in the infralimbic cortex is necessary for control of impulsive responding on the 5CSRTT. These results suggest a dissociable role for prefronto-cortical glutamatergic systems in response inhibition, which appear to be functionally localised to the ventromedial infralimbic area of the mPFC.

Animals↗
PubMed2005

The hippocampus and appetitive Pavlovian conditioning: effects of excitotoxic hippocampal lesions on conditioned locomotor activity and autoshaping.

The hippocampus (HPC) is known to be critically involved in the formation of associations between contextual/spatial stimuli and behaviorally significant events, playing a pivotal role in learning and memory. However, increasing evidence indicates that the HPC is also essential for more basic motivational processes. The amygdala, by contrast, is important for learning about the motivational significance of discrete cues. This study investigated the effects of excitotoxic lesions of the rat HPC and the basolateral amygdala (BLA) on the acquisition of a number of appetitive behaviors known to be dependent on the formation of Pavlovian associations between a reward (food) and discrete stimuli or contexts: (1) conditioned/anticipatory locomotor activity to food delivered in a specific context and (2) autoshaping, where rats learn to show conditioned discriminated approach to a discrete visual CS+. While BLA lesions had minimal effects on conditioned locomotor activity, hippocampal lesions facilitated the development of both conditioned activity to food and autoshaping behavior, suggesting that hippocampal lesions may have increased the incentive motivational properties of food and associated conditioned stimuli, consistent with the hypothesis that the HPC is involved in inhibitory processes in appetitive conditioning.

Amygdala↗
PubMed2005

Executive function in Tourette's syndrome and obsessive-compulsive disorder.

BACKGROUND: Cognitive performance was compared in the genetically and neurobiologically related disorders of Tourette's syndrome (TS) and obsessive-compulsive disorder (OCD), in three domains of executive function: planning, decision-making and inhibitory response control. METHOD: Twenty TS patients, twenty OCD patients and a group of age- and IQ-matched normal controls completed psychometric and computerized cognitive tests and psychiatric rating scales. The cognitive tests were well-characterized in terms of their sensitivity to other fronto-striatal disorders, and included pattern and spatial recognition memory, attentional set-shifting, and a Go/No-go set-shifting task, planning, and decision-making. RESULTS: Compared to controls, OCD patients showed selective deficits in pattern recognition memory and slower responding in both pattern and spatial recognition, impaired extra-dimensional shifting on the set-shifting test and impaired reversal of response set on the Go/No-go test. In contrast, TS patients were impaired in spatial recognition memory, extra-dimensional set-shifting, and decision-making. Neither group was impaired in planning. Direct comparisons between the TS and OCD groups revealed significantly different greater deficits for recognition memory latency and Go/No-go reversal for the OCD group, and quality of decision-making for the TS group. CONCLUSIONS: TS and OCD show both differences (recognition memory, decision-making) and similarities (set-shifting) in selective profiles of cognitive function. Specific set-shifting deficits in the OCD group contrasted with their intact performance on other tests of executive function, such as planning and decision-making, and suggested only limited involvement of frontal lobe dysfunction, possibly consistent with OCD symptomatology.

Adult↗