21 results on '"Danielle C. Turner"'
Search Results
2. Ketamine effects on memory reconsolidation favor a learning model of delusions.
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Philip R Corlett, Victoria Cambridge, Jennifer M Gardner, Jennifer S Piggot, Danielle C Turner, Jessica C Everitt, Fernando Sergio Arana, Hannah L Morgan, Amy L Milton, Jonathan L Lee, Michael R F Aitken, Anthony Dickinson, Barry J Everitt, Anthony R Absalom, Ram Adapa, Naresh Subramanian, Jane R Taylor, John H Krystal, and Paul C Fletcher more...
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Medicine ,Science - Abstract
Delusions are the persistent and often bizarre beliefs that characterise psychosis. Previous studies have suggested that their emergence may be explained by disturbances in prediction error-dependent learning. Here we set up complementary studies in order to examine whether such a disturbance also modulates memory reconsolidation and hence explains their remarkable persistence. First, we quantified individual brain responses to prediction error in a causal learning task in 18 human subjects (8 female). Next, a placebo-controlled within-subjects study of the impact of ketamine was set up on the same individuals. We determined the influence of this NMDA receptor antagonist (previously shown to induce aberrant prediction error signal and lead to transient alterations in perception and belief) on the evolution of a fear memory over a 72 hour period: they initially underwent Pavlovian fear conditioning; 24 hours later, during ketamine or placebo administration, the conditioned stimulus (CS) was presented once, without reinforcement; memory strength was then tested again 24 hours later. Re-presentation of the CS under ketamine led to a stronger subsequent memory than under placebo. Moreover, the degree of strengthening correlated with individual vulnerability to ketamine's psychotogenic effects and with prediction error brain signal. This finding was partially replicated in an independent sample with an appetitive learning procedure (in 8 human subjects, 4 female). These results suggest a link between altered prediction error, memory strength and psychosis. They point to a core disruption that may explain not only the emergence of delusional beliefs but also their persistence. more...
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- 2013
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3. Association Between Response Inhibition and Working Memory in Adult ADHD: A Link to Right Frontal Cortex Pathology?
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Jonathan H. Dowson, Trevor W. Robbins, Barbara J. Sahakian, Andrew D. Blackwell, Danielle C. Turner, Luke Clark, and Adam R. Aron
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Adult ,Male ,Pathology ,medicine.medical_specialty ,Short-term memory ,Inferior frontal gyrus ,Neuropsychological Tests ,Impulsivity ,Severity of Illness Index ,behavioral disciplines and activities ,Spatial memory ,Functional Laterality ,Reaction Time ,medicine ,Humans ,Prefrontal cortex ,Biological Psychiatry ,Memory Disorders ,Working memory ,Cognition ,Frontal Lobe ,Inhibition, Psychological ,Memory, Short-Term ,Frontal lobe ,Attention Deficit Disorder with Hyperactivity ,Space Perception ,Female ,medicine.symptom ,Psychology - Abstract
Background We sought to assess the relationship between response inhibition and working memory in adult patients with attention-deficit/hyperactivity disorder (ADHD) and neurosurgical patients with frontal lobe damage. Methods The stop-signal reaction time (SSRT) test and a spatial working memory (SWM) task were administered to 20 adult patients with ADHD and a group of matched controls. The same tasks were administered to 21 patients with lesions to right frontal cortex and 19 patients with left frontal lesions. Results The SSRT test, but not choice reaction time, was significantly associated with search errors on the SWM task in both the adult ADHD and right frontal patients. In the right frontal patients, impaired performance on both variables was correlated with the volume of damage to the inferior frontal gyrus. Conclusions Response inhibition and working memory impairments in ADHD may stem from a common pathologic process rather than being distinct deficits. Such pathology could relate to right frontal-cortex abnormalities in ADHD, consistent with prior reports, as well as with the demonstration here of a significant association between SSRT and SWM in right frontal patients. more...
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- 2007
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4. A Review of the Effects of Modafinil on Cognition in Schizophrenia
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Barbara J. Sahakian, Danielle C. Turner, and Sharon Morein-Zamir
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Psychosis ,medicine.medical_specialty ,Methylphenidate ,Modafinil ,Cognition ,Neuropsychological Tests ,medicine.disease ,Executive functions ,Severity of Illness Index ,Psychiatry and Mental health ,Schizophrenia ,Theme: The Orexins/Hypocretins and Schizophrenia Ariel Y. Deutch ,mental disorders ,medicine ,Humans ,Cognitive skill ,Effects of sleep deprivation on cognitive performance ,Benzhydryl Compounds ,Cognition Disorders ,Psychology ,Psychiatry ,medicine.drug - Abstract
Modafinil, a wake-promoting agent believed to operate via the hypocretin/orexin system, has a similar clinical profile to that of conventional, dopaminergic stimulants but different biochemical and pharmacological properties. There is increasing interest in the use of modafinil to improve cognition in schizophrenia as well as in other disorders such as attention-deficit/hyperactivity disorder. Recent research has focused on enhancing cognition in patients with schizophrenia because of the association between cognitive performance and functional outcome. Initial findings indicate that modafinil may lead to better executive functioning and attentional performance in patients with schizophrenia. The results further suggest that patient characteristics such as overall current cognitive functioning levels, genetic polymorphisms, and medication status may be important mediators for the effectiveness of modafinil, allowing for future treatment to be targeted to those most likely to benefit. Currently, further research is required to address the potential benefits and risks of chronic administration of modafinil to patients with schizophrenia. more...
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- 2006
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5. A review of the use of modafinil for attention-deficit hyperactivity disorder
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Danielle C. Turner
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medicine.medical_specialty ,General Neuroscience ,medicine.medical_treatment ,Modafinil ,medicine.disease ,Placebo ,behavioral disciplines and activities ,Stimulant ,Clinical trial ,Attention Deficit Disorder with Hyperactivity ,mental disorders ,medicine ,Insomnia ,Humans ,Attention deficit hyperactivity disorder ,Pharmacology (medical) ,Neurology (clinical) ,Benzhydryl Compounds ,Once daily ,medicine.symptom ,Psychiatry ,Psychology ,Adverse effect ,medicine.drug - Abstract
Modafinil (Provigil) is a novel wakefulness-promoting agent that has been shown to have greater efficacy than placebo in the treatment of attention-deficit hyperactivity disorder (ADHD) in children and adults. In particular, three large, drug-company sponsored trials of a film-coated formulation of modafinil (modafinil-ADHD; Sparlon) in children and adolescents with ADHD demonstrated consistent improvements in ADHD symptoms compared with placebo. Mean reductions in symptom ratings (measured using the ADHD-Rating Scale-IV school version questionnaire) ranged from 15.0 to 19.7 (7.3 to 10.1 for placebo). The most common adverse events were insomnia, headache and decreased appetite. Modafinil was generally well tolerated with most side effects considered mild to moderate in severity. Modafinil may have advantages over current therapies for ADHD in that it can be administered once daily and has fewer reinforcing properties than traditional stimulants. Modafinil could potentially be a valuable new treatment option for patients with ADHD. However, rigorous comparative studies with current first-line treatments for ADHD and longer-term independent studies are necessary before modafinil's role in the treatment of ADHD can be fully established. more...
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- 2006
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6. Neuroethics of Cognitive Enhancement
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Barbara J. Sahakian and Danielle C. Turner
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education.field_of_study ,medicine.medical_specialty ,Health (social science) ,ComputingMilieux_THECOMPUTINGPROFESSION ,Emerging technologies ,Health Policy ,Population ,Medical tourism ,Cognition ,Diathesis–stress model ,Harm ,medicine ,Engineering ethics ,education ,Psychiatry ,Psychology ,Neuroethics ,Dopamine hypothesis of schizophrenia - Abstract
The prospect of being able to take safe and effective drugs to improve mental functioning is becoming a reality. With the potential for widespread use of cognitive enhancers by large sectors of the population, this article discusses the rationale behind the development of these drugs and how society might benefit from them. Important ethical questions and scenarios are also raised. Scientists are urged to explore the implications of their work and engage in active debate with a wide range of interested stakeholders about the ethical and moral consequences of these new technologies to ensure maximal benefit with minimal harm. more...
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- 2006
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7. Analysis of the Cognitive Enhancing Effects of Modafinil in Schizophrenia
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Barbara J. Sahakian and Danielle C. Turner
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Psychiatry and Mental health ,medicine.medical_specialty ,Neurology ,business.industry ,Schizophrenia (object-oriented programming) ,Modafinil ,Medicine ,Cognition ,Neurology (clinical) ,business ,Psychiatry ,High functioning ,medicine.drug - Published
- 2006
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8. The Effects of a Subpsychotic Dose of Ketamine on Recognition and Source Memory for Agency: Implications for Pharmacological Modelling of Core Symptoms of Schizophrenia
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Garry D. Honey, Edith Pomarol-Clotet, Philip R. Corlett, Chris O'loughlin, Danielle C. Turner, and Paul C. Fletcher
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Adult ,Male ,Psychosis ,medicine.medical_specialty ,Adolescent ,Models, Psychological ,Neuropsychological Tests ,Audiology ,Verbal learning ,behavioral disciplines and activities ,Article ,Double-Blind Method ,medicine ,Humans ,Psychiatry ,Levels-of-processing effect ,Recognition memory ,Pharmacology ,Memory Disorders ,Memoria ,Recognition, Psychology ,Cognition ,Verbal Learning ,medicine.disease ,Psychiatry and Mental health ,Schizophrenia ,Mental Recall ,Female ,Ketamine ,Schizophrenic Psychology ,Psychology ,Excitatory Amino Acid Antagonists ,Psychopathology - Abstract
Ketamine is increasingly used to model the cognitive deficits and symptoms of schizophrenia. We investigated the extent to which ketamine administration in healthy volunteers reproduces the deficits in episodic recognition memory and agency source monitoring reported in schizophrenia. Intravenous infusions of placebo or 100 ng/ml ketamine were administered to 12 healthy volunteers in a double-blind, placebo-controlled, randomized, within-subjects study. In response to presented words, the subject or experimenter performed a deep or shallow encoding task, providing a 2(drug) × 2(depth of processing) × 2(agency) factorial design. At test, subjects discriminated old/new words, and recalled the sources (task and agent). Data were analyzed using multinomial modelling to identify item recognition, source memory for agency and task, and guessing biases. Under ketamine, item recognition and cued recall of deeply encoded items were impaired, replicating previous findings. In contrast to schizophrenia, there was a reduced tendency to externalize agency source guessing biases under ketamine. While the recognition memory deficit observed with ketamine is consistent with previous work and with schizophrenia, the changes in source memory differ from those reported in schizophrenic patients. This difference may account for the pattern of psychopathology induced by ketamine. more...
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- 2005
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9. Neurocognitive effects of methylphenidate in adult attention-deficit/hyperactivity disorder
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A McLean, Jonathan H. Dowson, Andrew D. Blackwell, Barbara J. Sahakian, and Danielle C. Turner
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Adult ,Male ,medicine.medical_specialty ,Neuropsychological Tests ,Impulsivity ,behavioral disciplines and activities ,Spatial memory ,Double-Blind Method ,Microcomputers ,Dopamine ,Orientation ,mental disorders ,medicine ,Humans ,Attention deficit hyperactivity disorder ,Attention ,Psychiatry ,Problem Solving ,Pain Measurement ,Pharmacology ,Cross-Over Studies ,Methylphenidate ,Working memory ,Cognition ,medicine.disease ,Memory, Short-Term ,Treatment Outcome ,Attention Deficit Disorder with Hyperactivity ,Central Nervous System Stimulants ,Female ,medicine.symptom ,Psychology ,Neurocognitive ,medicine.drug - Abstract
Features of childhood attention-deficit/hyperactivity disorder (ADHD) often persist into adulthood. It has been shown that adult ADHD is associated with various neurocognitive deficits, including impairments in spatial working memory (SWM) and attention. It is not known whether these deficits are ameliorated by methylphenidate in adult ADHD.The aim of this study was to evaluate the neurocognitive effects of a single dose of methylphenidate on SWM, visual memory, spatial span and sustained attention in adult ADHD.Twenty-four adult patients, recruited from a specialised clinic for the assessment of adult ADHD, were entered into a double-blind, randomised, placebo-controlled crossover study using a single 30 mg dose of methylphenidate.Eighteen patients met DSM-IV criteria for adult ADHD. Methylphenidate resulted in an improvement in SWM performance and sustained attention, together with a speeding in response time, in these patients. Six patients with attentional difficulties, who did not meet a DSM-IV diagnosis of ADHD, showed a different pattern of response to methylphenidate compared to the ADHD group. For the combined group, moderate correlations were shown between childhood ratings of ADHD (both self-reported and informant ratings) and response to methylphenidate on the SWM task.Adults with ADHD had a similar neurocognitive response to methylphenidate to that previously reported for childhood ADHD. Our results provide further support for the validity of the ADHD syndrome as defined by DSM-IV and indicate possible neurocognitive substrates for clinical improvement with chronic methylphenidate. more...
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- 2004
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10. The Role of the Lateral Frontal Cortex in Causal Associative Learning: Exploring Preventative and Super-learning
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Trevor W. Robbins, Michael R. F. Aitken, Christian Schwarzbauer, Barbara J. Sahakian, David R. Shanks, Danielle C. Turner, and Paul C. Fletcher
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Adult ,Male ,Cognitive Neuroscience ,Brain mapping ,Article ,Cellular and Molecular Neuroscience ,medicine ,Humans ,Prefrontal cortex ,Evoked Potentials ,Anterior cingulate cortex ,Associative property ,Neurons ,Brain Mapping ,medicine.diagnostic_test ,Working memory ,Novelty ,Association Learning ,Magnetic Resonance Imaging ,Frontal Lobe ,Associative learning ,medicine.anatomical_structure ,Female ,Psychology ,Functional magnetic resonance imaging ,Cognitive psychology - Abstract
Prediction error — a mismatch between expected and actual outcome — is critical to associative accounts of inferential learning. However, it has proven difficult to explore the effects of prediction error using functional magnetic resonance imaging (fMRI) while excluding the confounding effects of stimulus novelty and incorrect responses. In this event-related fMRI study we used a three-stage experiment generating preventative- and super-learning conditions. In both cases, it was possible to generate prediction error within a causal associative learning experiment while subtracting the effects of novelty and error. We show that right lateral prefrontal cortex (PFC) activation is sensitive to the magnitude of prediction error. Furthermore, super-learning activation in this region of PFC correlates, across subjects, with the amount learned. We thus provide direct evidence for a brain correlate of the surprise-dependent mechanisms proposed by associative accounts of causal learning. We show that activity in right lateral PFC is sensitive to the magnitude, though not the direction, of the prediction error. Furthermore, its activity is not directly explicable in terms of novelty or response errors and appears directly related to the learning that arises out of prediction error. more...
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- 2004
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11. Relative lack of cognitive effects of methylphenidate in elderly male volunteers
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Luke Clark, Danielle C. Turner, Adam R. Aron, Jonathan H. Dowson, Barbara J. Sahakian, and Trevor W. Robbins
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Central Nervous System ,Male ,medicine.medical_specialty ,Administration, Oral ,Neuropsychological Tests ,law.invention ,Cardiovascular Physiological Phenomena ,Cognition ,Randomized controlled trial ,Risk Factors ,law ,Monoaminergic ,Reaction Time ,medicine ,Humans ,Psychiatry ,Aged ,Pain Measurement ,Pharmacology ,Dose-Response Relationship, Drug ,Methylphenidate ,Working memory ,Dopaminergic ,Age Factors ,Middle Aged ,Reuptake inhibitor ,Psychology ,medicine.drug ,Clinical psychology ,Executive dysfunction - Abstract
Methylphenidate, a dopaminergic and noradrenergic reuptake inhibitor, has been shown in young, healthy adult volunteers to produce pronounced effects on working memory and sustained attention. We were interested in assessing whether similar improvements could be conferred upon elderly volunteers in order to gain a more complete understanding of the effects of age on monoaminergic manipulations of working memory and attention, as well as to explore the potential for pharmacological intervention in attention and executive dysfunction disorders in this age group.The main aim of the study was to characterise the dose-related effects of methylphenidate on a range of neuropsychological functions in elderly healthy volunteers.Sixty healthy elderly adult male volunteers received either a single oral dose of placebo, 20 mg or 40 mg methylphenidate prior to performing a variety of tasks designed to assess memory, attention and executive function. A randomised double-blind, between-subjects design was used.Methylphenidate had significant cardiovascular and subjective effects. However, unlike in younger volunteers, no significant effects of drug on working memory (spatial span and spatial working memory), response inhibition (stop-signal) or sustained attention (rapid visual information processing) were seen. Subtle effects on latency similar to those in younger volunteers were identified: both doses of methylphenidate resulted in a slowing in response time during set-shifting and decision-making.The results of this study demonstrate that, in elderly subjects, the cognitive effects of methylphenidate are grossly attenuated and distinct from the profile previously described in younger volunteers. It is suggested that methylphenidate may not be appropriate as a pharmacological intervention in elderly patient groups, such as those reporting age-related cognitive decline. more...
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- 2003
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12. Cognitive enhancing effects of modafinil in healthy volunteers
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Barbara J. Sahakian, Trevor W. Robbins, Adam R. Aron, Danielle C. Turner, Jonathan H. Dowson, and Luke Clark
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Adult ,Male ,medicine.medical_specialty ,Decision Making ,Blood Pressure ,Modafinil ,Audiology ,Spatial memory ,Cognition ,Double-Blind Method ,Heart Rate ,Memory ,medicine ,Memory span ,Humans ,Attention deficit hyperactivity disorder ,Benzhydryl Compounds ,Pain Measurement ,Pharmacology ,Psychological Tests ,Dose-Response Relationship, Drug ,Methylphenidate ,Working memory ,Memoria ,medicine.disease ,Neuroprotective Agents ,Pattern Recognition, Visual ,Psychology ,medicine.drug ,Cognitive psychology - Abstract
Rationale. Modafinil, a novel wake-promoting agent, has been shown to have a similar clinical profile to that of conventional stimulants such as methylphenidate. We were therefore interested in assessing whether modafinil, with its unique pharmacological mode of action, might offer similar potential as a cognitive enhancer, without the side effects commonly experienced with amphetamine-like drugs. Objectives. The main aim of this study was to evaluate the cognitive enhancing potential of this novel agent using a comprehensive battery of neuropsychological tests. Methods. Sixty healthy young adult male volunteers received either a single oral dose of placebo, or 100 mg or 200 mg modafinil prior to performing a variety of tasks designed to test memory and attention. A randomised double-blind, between-subjects design was used. Results. Modafinil significantly enhanced performance on tests of digit span, visual pattern recognition memory, spatial planning and stop-signal reaction time. These performance improvements were complemented by a slowing in latency on three tests: delayed matching to sample, a decision-making task and the spatial planning task. Subjects reported feeling more alert, attentive and energetic on drug. The effects were not clearly dose dependent, except for those seen with the stop-signal paradigm. In contrast to previous findings with methylphenidate, there were no significant effects of drug on spatial memory span, spatial working memory, rapid visual information processing or attentional set-shifting. Additionally, no effects on paired associates learning were identified. Conclusions. These data indicate that modafinil selectively improves neuropsychological task performance. This improvement may be attributable to an enhanced ability to inhibit pre-potent responses. This effect appears to reduce impulsive responding, suggesting that modafinil may be of benefit in the treatment of attention deficit hyperactivity disorder. more...
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- 2003
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13. Ketamine Effects on Memory Reconsolidation Favor a Learning Model of Delusions
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Jennifer S. Piggot, Jane R. Taylor, Michael R. F. Aitken, Anthony Absalom, Fernando S. Arana, Anthony Dickinson, Hannah L. Morgan, John H. Krystal, Danielle C. Turner, Jennifer M. Gardner, Philip R. Corlett, Ram Adapa, Jonathan L.C. Lee, Naresh Subramanian, Paul C. Fletcher, Jessica C. Everitt, Victoria C. Cambridge, Barry J. Everitt, Amy L. Milton, Critical care, Anesthesiology, Peri-operative and Emergency medicine (CAPE), Milton, Amy [0000-0003-0175-9417], Everitt, Barry [0000-0003-4431-6536], Fletcher, Paul [0000-0001-8257-1517], and Apollo - University of Cambridge Repository more...
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Male ,Conditioning, Classical ,lcsh:Medicine ,PREFRONTAL CORTEX ,Social and Behavioral Sciences ,0302 clinical medicine ,Learning and Memory ,POSTTRAUMATIC-STRESS-DISORDER ,Psychology ,Fear conditioning ,Prefrontal cortex ,lcsh:Science ,Psychiatry ,0303 health sciences ,PREDICTION-ERROR SIGNAL ,Multidisciplinary ,medicine.diagnostic_test ,SPONTANEOUS CONFABULATION ,Fear ,KAMIN BLOCKING ,FRONTAL-CORTEX ,Magnetic Resonance Imaging ,Mental Health ,Neurology ,NMDA receptor ,Medicine ,Memory consolidation ,Female ,Ketamine ,Research Article ,Adult ,medicine.medical_specialty ,Psychosis ,Cognitive Neuroscience ,Neuroimaging ,SCHIZOPHRENIA-PATIENTS ,Receptors, N-Methyl-D-Aspartate ,INDIVIDUAL-DIFFERENCES ,Delusions ,03 medical and health sciences ,Memory ,medicine ,Learning ,Humans ,Working Memory ,Set (psychology) ,Biology ,030304 developmental biology ,FEAR MEMORIES ,lcsh:R ,Cognitive Psychology ,Classical conditioning ,Psychoses ,Association Learning ,medicine.disease ,Case-Control Studies ,Schizophrenia ,lcsh:Q ,Functional magnetic resonance imaging ,Neuroscience ,030217 neurology & neurosurgery ,HEALTHY-VOLUNTEERS - Abstract
Delusions are the persistent and often bizarre beliefs that characterise psychosis. Previous studies have suggested that their emergence may be explained by disturbances in prediction error-dependent learning. Here we set up complementary studies in order to examine whether such a disturbance also modulates memory reconsolidation and hence explains their remarkable persistence. First, we quantified individual brain responses to prediction error in a causal learning task in 18 human subjects (8 female). Next, a placebo-controlled within-subjects study of the impact of ketamine was set up on the same individuals. We determined the influence of this NMDA receptor antagonist (previously shown to induce aberrant prediction error signal and lead to transient alterations in perception and belief) on the evolution of a fear memory over a 72 hour period: they initially underwent Pavlovian fear conditioning; 24 hours later, during ketamine or placebo administration, the conditioned stimulus (CS) was presented once, without reinforcement; memory strength was then tested again 24 hours later. Re-presentation of the CS under ketamine led to a stronger subsequent memory than under placebo. Moreover, the degree of strengthening correlated with individual vulnerability to ketamine's psychotogenic effects and with prediction error brain signal. This finding was partially replicated in an independent sample with an appetitive learning procedure (in 8 human subjects, 4 female). These results suggest a link between altered prediction error, memory strength and psychosis. They point to a core disruption that may explain not only the emergence of delusional beliefs but also their persistence. more...
- Published
- 2013
14. Methamphetamine-induced disruption of frontostriatal reward learning signals: relation to psychotic symptoms
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Trevor W. Robbins, Brady McFarlane, Pranathi Ramachandra, Danielle C. Turner, Luke Clark, Philip R. Corlett, Javier Bernacer, Graham K. Murray, and Paul C. Fletcher
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Adult ,Male ,Psychosis ,Prefrontal Cortex ,Placebo ,Basal Ganglia ,Nucleus Accumbens ,Developmental psychology ,Methamphetamine ,Reward ,Functional neuroimaging ,medicine ,Reinforcement learning ,Humans ,Learning ,Amisulpride ,Reinforcement ,Functional Neuroimaging ,medicine.disease ,Magnetic Resonance Imaging ,Corpus Striatum ,Psychiatry and Mental health ,Psychotic Disorders ,Schizophrenia ,Central Nervous System Stimulants ,Female ,Sulpiride ,Psychology ,Neuroscience ,Reinforcement, Psychology ,medicine.drug ,Antipsychotic Agents - Abstract
Frontostriatal circuitry is critical to learning processes, and its disruption may underlie maladaptive decision making and the generation of psychotic symptoms in schizophrenia. However, there is a paucity of evidence directly examining the role of modulatory neurotransmitters on frontostriatal function in humans. In order to probe the effects of modulation on frontostriatal circuitry during learning and to test whether disruptions in learning processes may be related to the pathogenesis of psychosis, the authors explored the brain representations of reward prediction error and incentive value, two key reinforcement learning parameters, before and after methamphetamine challenge.Healthy volunteers (N=18) underwent functional MRI (fMRI) scanning while performing a reward learning task on three occasions: after placebo, after methamphetamine infusion (0.3 mg/kg body weight), and after pretreatment with 400 mg of amisulpride and then methamphetamine infusion. Brain fMRI representations of learning signals, calculated using a reinforcement Q-learning algorithm, were compared across drug conditions.In the placebo condition, reward prediction error was coded in the ventral striatum bilaterally and incentive value in the ventromedial prefrontal cortex bilaterally. Reward prediction error and incentive value signals were disrupted by methamphetamine in the left nucleus accumbens and left ventromedial prefrontal cortex, respectively. Psychotic symptoms were significantly correlated with incentive value disruption in the ventromedial prefrontal and posterior cingulate cortex. Amisulpride pretreatment did not significantly alter methamphetamine-induced effects.The results demonstrate that methamphetamine impairs brain representations of computational parameters that underpin learning. They also demonstrate a significant link between psychosis and abnormal monoamine-regulated learning signals in the prefrontal and cingulate cortices. more...
- Published
- 2013
15. Ketamine administration in healthy volunteers reproduces aberrant agency experiences associated with schizophrenia
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Jessica C. Everitt, Hannah L. Morgan, Jennifer Pigott, Jenny Gardner, Fernando S. Arana, Ram Adapa, James W. Moore, Patrick Haggard, Paul C. Fletcher, Antony R. Absalom, Sanne de Wit, Danielle C. Turner, Philip R. Corlett, Ontwikkelingspsychologie (Psychologie, FMG), and Klinische Psychologie (Psychologie, FMG) more...
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Male ,Volition ,SYMPTOMS ,EMISSION-TOMOGRAPHY PET ,0302 clinical medicine ,Young adult ,DELUSIONS ,05 social sciences ,Cognitive disorder ,INTENTION ,Voluntary action ,CONSCIOUS AWARENESS ,Healthy Volunteers ,Psychiatry and Mental health ,Schizophrenia ,Female ,Ketamine ,PREDICTION-ERROR ,Psychology ,Research Article ,medicine.drug ,Adult ,Psychosis ,medicine.medical_specialty ,Cognitive Neuroscience ,Sensation ,Models, Psychological ,Placebo ,behavioral disciplines and activities ,Psychoses, Substance-Induced ,050105 experimental psychology ,BODY-OWNERSHIP ,Sense of agency ,Judgment ,Young Adult ,03 medical and health sciences ,PSYCHOSIS ,medicine ,Humans ,0501 psychology and cognitive sciences ,Psychiatry ,Dose-Response Relationship, Drug ,MEMORY ,medicine.disease ,Action-outcome binding ,Excitatory Amino Acid Antagonists ,030217 neurology & neurosurgery - Abstract
Introduction. Aberrant experience of agency is characteristic of schizophrenia. An understanding of the neurobiological basis of such experience is therefore of considerable importance for developing successful models of the disease. We aimed to characterise the effects of ketamine, a drug model for psychosis, on sense of agency (SoA). SoA is associated with a subjective compression of the temporal interval between an action and its effects: This is known as "intentional binding". This action-effect binding provides an indirect measure of SoA. Previous research has found that the magnitude of binding is exaggerated in patients with schizophrenia. We therefore investigated whether ketamine administration to otherwise healthy adults induced a similar pattern of binding.Methods. 14 right-handed healthy participants (8 female; mean age 22.4 years) were given low-dose ketamine (100 ng/mL plasma) and completed the binding task. They also underwent structured clinical interviews.Results. Ketamine mimicked the performance of schizophrenia patients on the intentional binding task, significantly increasing binding relative to placebo. The size of this effect also correlated with aberrant bodily experiences engendered by the drug.Conclusions. These data suggest that ketamine may be able to mimic certain aberrant agency experiences that characterise schizophrenia. The link to individual changes in bodily experience suggests that the fundamental change produced by the drug has wider consequences in terms of individuals' experiences of their bodies and movements. more...
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- 2011
16. Association between serotonin transporter binding, physiological and environmental factors in healthy male subjects
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Sam R. Miller, Eugenii A. Rabiner, Venkatesha Murthy, Paul M. Grasby, Zubin Bhagwagar, Wim J. Riedel, Polly V. Peers, Danielle C. Turner, Robert A. Comley, Neuropsychology & Psychopharmacology, and RS: FPN NPPP II more...
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medicine.medical_specialty ,Endocrinology ,Neurology ,biology ,business.industry ,Cognitive Neuroscience ,Internal medicine ,medicine ,biology.protein ,Association (psychology) ,business ,Serotonin transporter - Published
- 2010
17. Experimental Psychology and Research into Brain Science, Addiction and Drugs
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Theodora Duka, Danielle C. Turner, and Barbara J. Sahakian
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Cognitive science ,Experimental psychology ,Addiction ,media_common.quotation_subject ,Psychoactive substance ,Psychoactive drug ,medicine ,Cognition ,Context (language use) ,Cognitive impairment ,Psychology ,media_common ,medicine.drug - Abstract
Publisher Summary Experimental psychology is ideally placed to determine the cognitive and emotional effects of psychoactive substances, and the contribution of cognition and emotion to addiction. This chapter illustrates the advances that are made in exploring the effects of psychoactive substance use using tools and techniques that focus on the understanding of learning, reward, motivation, and cognition. This understanding is central for preventing and treating the devastating effects of psychoactive drug addiction and improving the quality of life for patients suffering from cognitive impairment. The understanding helps to develop robust theories of human behavior in the context of psychoactive substance use. The chapter focuses mainly on drugs, but it is possible that in the future many of the same considerations apply to nonchemical approaches such as transcranial magnetic stimulation or neural prosthetics. The chapter describes how one uses experimental psychology to embrace the new opportunities presenting themselves as our insight into psychotropic drugs, addiction, and cognitive enhancement deepens. It is thus imperative to use experimental psychology paradigms to screen drugs to ensure the safest possible use of current and future psychotropic effects. more...
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- 2007
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18. Questionnaire ratings of attention-deficit/hyperactivity disorder (ADHD) in adults are associated with spatial working memory
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Tina Malhotra, Elizabeth J. Harvey, Trevor W. Robbins, Barbara J. Sahakian, Jonathan H. Dowson, Andrew D. Blackwell, and Danielle C. Turner
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Adult ,Male ,050103 clinical psychology ,medicine.medical_specialty ,Psychometrics ,Neuropsychological Tests ,Impulsivity ,Spatial memory ,Severity of Illness Index ,03 medical and health sciences ,0302 clinical medicine ,Surveys and Questionnaires ,medicine ,Attention deficit hyperactivity disorder ,Humans ,0501 psychology and cognitive sciences ,Interpersonal Relations ,Diagnosis, Computer-Assisted ,Psychiatry ,Memory Disorders ,Working memory ,05 social sciences ,Brain ,Reproducibility of Results ,Cognition ,medicine.disease ,030227 psychiatry ,Diagnostic and Statistical Manual of Mental Disorders ,Disruptive, Impulse Control, and Conduct Disorders ,Psychiatry and Mental health ,Affect ,Mood ,Memory, Short-Term ,Attention Deficit Disorder with Hyperactivity ,Space Perception ,Female ,medicine.symptom ,Psychology ,Neurocognitive - Abstract
ObjectiveData related to brain function may have the potential to improve the reliability and validity of assessments for the aetiologically and clinically heterogeneous syndrome of attention-deficit/hyperactivity disorder (ADHD). This study investigated associations between questionnaire assessments of behavioural features of adults with ADHD and an aspect of neurocognitive performance which has been reported to be impaired in adults with ADHD.MethodsFifty-nine adult patients with a DSM-IV diagnosis of ADHD, and their informants, completed questionnaires related to aspects of severity of ADHD. Associations were examined between questionnaire ratings and performance on a computer-administered task of spatial working memory (SWM).ResultsCorrelations between ratings of ADHD and SWM indicated moderate but significant correlations for patients' ratings, but not for informants' ratings. Also, patients who reported a past history of ‘self-harm’ (N = 33) had a significantly worse mean performance on both measures of SWM (p = 0.004, 0.003).ConclusionsThe results indicate that aspects of impulsivity, i.e. self-ratings of ‘emotive’ behaviour (involving rapid response to stimuli and marked reactivity of mood) and of past ‘self-harm’, show relatively strong associations with SWM performance in adults selected on the basis of an ADHD diagnosis. A profile of neurocognitive performances may have a role in the assessment of ADHD. more...
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- 2006
19. Impairment of specific episodic memory processes by sub-psychotic doses of ketamine: the effects of levels of processing at encoding and of the subsequent retrieval task
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Edith Pomarol-Clotet, Dharshan Kumaran, R.A.E. Honey, Danielle C. Turner, Edward T. Bullmore, Paul C. Fletcher, Sam R. Sharar, Michael D. Rugg, Garry D. Honey, Xiangen Hu, and Jon S. Simons
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Adult ,Male ,Psychosis ,N-Methylaspartate ,Adolescent ,Double-Blind Method ,Memory ,medicine ,Humans ,Levels-of-processing effect ,Infusions, Intravenous ,Episodic memory ,Recognition memory ,Pharmacology ,Recall ,Dose-Response Relationship, Drug ,Working memory ,Retention, Psychology ,Cognition ,Middle Aged ,Verbal Learning ,medicine.disease ,Schizophrenia ,Female ,Ketamine ,Psychology ,Arousal ,Neuroscience - Abstract
The precise nature of the impact of the N-methyl-d-aspartate antagonist, ketamine, upon human episodic memory, has yet to be elucidated fully. This study sought to assess the effects of ketamine on the sub-processes facilitating memory encoding and retrieval. We evaluated the effects of the drug on a series of memory performance measures depending upon whether it was administered at the encoding or retrieval stage and on the nature of the encoding task used. Twelve healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. Intravenous infusions of placebo, 50 ng/ml ketamine or 100 ng/ml ketamine were administered. We investigated the effects of ketamine on three key aspects of episodic memory: encoding vs retrieval processes, source memory, and depth of processing. Data were analysed using both multinomial modelling and standard measures of item discrimination and response bias. Deleterious effects of ketamine on episodic memory were primarily attributable to its effects on encoding, rather than retrieval processes. Recognition memory was impaired for items encoded at an intermediate level of processing, but preserved for shallowly and deeply encoded items. Increased source guessing bias was also observed when encoding took place under ketamine. The effects of ketamine upon episodic memory seem, therefore, to predominate at encoding. Furthermore, our results are also consistent with a specific impairment of encoding processes that result in subsequent recollective, as opposed to familiarity-based, retrieval. The observed effects are compatible with memory deficits seen in schizophrenia and thus provide some support for the ketamine model of the disease. more...
- Published
- 2004
20. Subdissociative dose ketamine produces a deficit in manipulation but not maintenance of the contents of working memory
- Author
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R.A.E. Honey, Paul C. Fletcher, Sam R. Sharar, Trevor W. Robbins, Barbara J. Sahakian, Edith Pomarol-Clotet, Garry D. Honey, Danielle C. Turner, Dharshan Kumaran, and Peter J. McKenna
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Adult ,Male ,medicine.medical_specialty ,Psychosis ,Adolescent ,Audiology ,Placebo ,behavioral disciplines and activities ,Article ,Double-Blind Method ,Memory ,medicine ,Humans ,Ketamine ,Prefrontal cortex ,Pharmacology ,Analysis of Variance ,Memory Disorders ,Working memory ,Memoria ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Schizophrenia ,Anesthesia ,Female ,Psychopharmacology ,Psychology ,medicine.drug - Abstract
We investigated the effects of subdissociative dose ketamine on executive processes during a working memory task. A total of 11 healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. They attended on three occasions, receiving intravenous infusions of placebo, a lower ketamine dose, and a higher ketamine dose. On each occasion, they underwent a series of tasks engaging working memory function in verbal and visuo-spatial domains. Further tasks explored aspects of long-term memory, planning, attention, and perceptual processing. With respect to working memory/executive function, a highly specific pattern of impairment was observed. Impairments were seen only at the higher dose of ketamine and restricted to a subgroup of the verbal working memory tasks: While visuo-spatial working memory showed no evidence of impairment, and while simple maintenance processes during verbal working memory were also unimpaired, higher dose ketamine produced a significant impairment in the manipulation of information within working memory. This process-specific effect of ketamine was reflected in a drug-by-task interaction. The specificity of this ketamine effect suggests that the earliest effect of NMDA receptor blockade is in higher order control of executive function rather than in more basic maintenance processes. more...
- Published
- 2003
21. Methylphenidate improves response inhibition but not reflection–impulsivity in children with attention deficit hyperactivity disorder (ADHD)
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Barbara J. Sahakian, Michael R. F. Aitken, Anna Maria Dezsery, Luke Clark, Andrew D. Blackwell, Lindsey Kent, Danielle C. Turner, and Elise E. DeVito
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Male ,Child Behavior ,Stop signal ,Neuropsychological Tests ,Disinhibition ,0302 clinical medicine ,Cognition ,Surveys and Questionnaires ,Child ,Response inhibition ,Original Investigation ,Cross-Over Studies ,Methylphenidate ,05 social sciences ,Inhibition, Psychological ,Treatment Outcome ,Research Design ,medicine.symptom ,Psychology ,Cognitive enhancement ,medicine.drug ,Clinical psychology ,medicine.medical_specialty ,Impulsivity ,Reflection–impulsivity ,Adolescent ,Decision Making ,Pharmacology toxicology ,050105 experimental psychology ,03 medical and health sciences ,Double-Blind Method ,mental disorders ,medicine ,ADHD ,Humans ,Attention deficit hyperactivity disorder ,0501 psychology and cognitive sciences ,Psychiatry ,Reflection (computer graphics) ,Pharmacology ,Motor planning ,business.industry ,medicine.disease ,Attention Deficit Disorder with Hyperactivity ,Impulsive Behavior ,Central Nervous System Stimulants ,business ,030217 neurology & neurosurgery ,Psychomotor Performance ,Decision-making - Abstract
Rationale Impulsivity is a cardinal feature of attention deficit hyperactivity disorder (ADHD), which is thought to underlie many of the cognitive and behavioural symptoms associated with the disorder. Impairments on some measures of impulsivity have been shown to be responsive to pharmacotherapy. However, impulsivity is a multi-factorial construct and the degree to which different forms of impulsivity contribute to impairments in ADHD or respond to pharmacological treatments remains unclear. Objectives The aims of the study were to assess the effects of methylphenidate (MPH) on the performance of children with ADHD on measures of reflection–impulsivity and response inhibition and to compare with the performance of healthy volunteers. Methods Twenty-one boys (aged 7–13 years) diagnosed with ADHD underwent a double-blind, placebo-controlled trial of MPH (0.5 mg/kg) during which they performed the Information Sampling Task (IST) and the Stop Signal Task. A healthy age- and education-matched control group was tested on the same measures without medication. Results Children with ADHD were impaired on measures of response inhibition, but did not demonstrate reflection–impulsivity on the IST. However, despite sampling a similar amount of information as their peers, the ADHD group made more poor decisions. MPH improved performance on measures of response inhibition and variability of response, but did not affect measures of reflection–impulsivity or quality of decision-making. Conclusions MPH differentially affected two forms of impulsivity in children with ADHD and failed to ameliorate their poor decision-making on the information sampling test. more...
- Published
- 2009
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