Publications (17)100.25 Total impact
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Article: Effects of pramipexole on the processing of rewarding and aversive taste stimuli.
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ABSTRACT: RATIONALE: Pramipexole, a D2/D3 dopamine receptor agonist, has been implicated in the development of impulse control disorders in patients with Parkinson's disease. Investigation of single doses of pramipexole in healthy participants in reward-based learning tasks has shown inhibition of the neural processing of reward, presumptively through stimulation of dopamine autoreceptors. OBJECTIVES: This study aims to examine the effects of pramipexole on the neural response to the passive receipt of rewarding and aversive sight and taste stimuli. METHODS: We used functional magnetic resonance imaging to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 16 healthy volunteers who received a single dose of pramipexole (0.25 mg) and placebo in a double-blind, within-subject, design. RESULTS: Relative to placebo, pramipexole treatment reduced blood oxygen level-dependent activation to the chocolate stimuli in the areas known to play a key role in reward, including the ventromedial prefrontal cortex, the orbitofrontal cortex, striatum, thalamus and dorsal anterior cingulate cortex. Pramipexole also reduced activation to the aversive condition in the dorsal anterior cingulate cortex. There were no effects of pramipexole on the subjective ratings of the stimuli. CONCLUSIONS: Our results are consistent with an ability of acute, low-dose pramipexole to diminish dopamine-mediated responses to both rewarding and aversive taste stimuli, perhaps through an inhibitory action of D2/3 autoreceptors on phasic burst activity of midbrain dopamine neurones. The ability of pramipexole to inhibit aversive processing might potentiate its adverse behavioural effects and could also play a role in its proposed efficacy in treatment-resistant depression.Psychopharmacologia 03/2013; · 4.08 Impact Factor -
Article: Increased resting state functional connectivity in the default mode network in recovered anorexia nervosa.
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ABSTRACT: Functional brain imaging studies have shown abnormal neural activity in individuals recovered from anorexia nervosa (AN) during both cognitive and emotional task paradigms. It has been suggested that this abnormal activity which persists into recovery might underpin the neurobiology of the disorder and constitute a neural biomarker for AN. However, no study to date has assessed functional changes in neural networks in the absence of task-induced activity in those recovered from AN. Therefore, the aim of this study was to investigate whole brain resting state functional connectivity in nonmedicated women recovered from anorexia nervosa. Functional magnetic resonance imaging scans were obtained from 16 nonmedicated participants recovered from anorexia nervosa and 15 healthy control participants. Independent component analysis revealed functionally relevant resting state networks. Dual regression analysis revealed increased temporal correlation (coherence) in the default mode network (DMN) which is thought to be involved in self-referential processing. Specifically, compared to healthy control participants the recovered anorexia nervosa participants showed increased temporal coherence between the DMN and the precuneus and the dorsolateral prefrontal cortex/inferior frontal gyrus. The findings support the view that dysfunction in resting state functional connectivity in regions involved in self-referential processing and cognitive control might be a vulnerability marker for the development of anorexia nervosa. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.Human Brain Mapping 10/2012; · 5.88 Impact Factor -
Article: Neural processing of reward and punishment in young people at increased familial risk of depression.
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ABSTRACT: Abnormalities in the neural representation of rewarding and aversive stimuli have been well-described in patients with acute depression, and we previously found abnormal neural responses to rewarding and aversive sight and taste stimuli in recovered depressed patients. The aim of the present study was to determine whether similar abnormalities might be present in young people at increased familial risk of depression but with no personal history of mood disorder. We therefore used functional magnetic resonance imaging to examine the neural responses to pleasant and aversive sights and tastes in 25 young people (16-21 years of age) with a biological parent with depression and 25 age- and gender-matched control subjects. We found that, relative to the control subjects, participants with a parental history of depression showed diminished responses in the orbitofrontal cortex to rewarding stimuli, whereas activations to aversive stimuli were increased in the lateral orbitofrontal cortex and insula. In anterior cingulate cortex the at-risk group showed blunted neural responses to both rewarding and aversive stimuli. Our findings suggest that young people at increased familial risk of depression have altered neural representation of reward and punishment, particularly in cortical regions linked to the use of positive and negative feedback to guide adaptive behavior.Biological psychiatry 06/2012; 72(7):588-94. · 8.93 Impact Factor -
Article: Neural responses to emotional faces in women recovered from anorexia nervosa.
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ABSTRACT: Impairments in emotional processing have been associated with anorexia nervosa. However, it is unknown whether neural and behavioural differences in the processing of emotional stimuli persist following recovery. The aim of this study was to investigate the neural processing of emotional faces in individuals recovered from anorexia nervosa compared with healthy controls. Thirty-two participants (16 recovered anorexia nervosa, 16 healthy controls) underwent a functional magnetic resonance imaging (fMRI) scan. Participants viewed fearful and happy emotional faces and indicated the gender of the face presented. Whole brain analysis revealed no significant differences between the groups to the contrasts of fear versus happy and vice versa. Region of interest analysis demonstrated no significant differences in the neural response to happy or fearful stimuli between the groups in the amygdala or fusiform gyrus. These results suggest that processing of emotional faces may not be aberrant after recovery from anorexia nervosa.Psychiatry Research 03/2012; 201(3):190-5. · 2.52 Impact Factor -
Article: Reply to: Punishing Food: What Brain Activity Can Tell Us About the Representation of Food in Recovered Anorexia Nervosa.
Biological psychiatry 12/2011; · 8.93 Impact Factor -
Article: Increased neural processing of rewarding and aversive food stimuli in recovered anorexia nervosa.
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ABSTRACT: Recent evidence has shown that individuals with acute anorexia nervosa and those recovered have aberrant physiological responses to rewarding stimuli. We hypothesized that women recovered from anorexia nervosa would show aberrant neural responses to both rewarding and aversive disorder-relevant stimuli. Using functional magnetic resonance imaging (fMRI), the neural response to the sight and flavor of chocolate, and their combination, in 15 women recovered from restricting-type anorexia nervosa and 16 healthy control subjects matched for age and body mass index was investigated. The neural response to a control aversive condition, consisting of the sight of moldy strawberries and a corresponding unpleasant taste, was also measured. Participants simultaneously recorded subjective ratings of "pleasantness," "intensity," and "wanting." Despite no differences between the groups in subjective ratings, individuals recovered from anorexia nervosa showed increased neural response to the pleasant chocolate taste in the ventral striatum and pleasant chocolate sight in the occipital cortex. The recovered participants also showed increased neural response to the aversive strawberry taste in the insula and putamen and to the aversive strawberry sight in the anterior cingulate cortex and caudate. Individuals recovered from anorexia nervosa have increased neural responses to both rewarding and aversive food stimuli. These findings suggest that even after recovery, women with anorexia nervosa have increased salience attribution to food stimuli. These results aid our neurobiological understanding and support the view that the neural response to reward may constitute a neural biomarker for anorexia nervosa.Biological psychiatry 06/2011; 70(8):736-43. · 8.93 Impact Factor -
Article: Antidepressant medications reduce subcortical-cortical resting-state functional connectivity in healthy volunteers.
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ABSTRACT: Studies have revealed abnormalities in resting-state functional connectivity in those with major depressive disorder specifically in areas such as the dorsal anterior cingulate, thalamus, amygdala, the pallidostriatum and subgenual cingulate. However, the effect of antidepressant medications on human brain function is less clear and the effect of these drugs on resting-state functional connectivity is unknown. Forty volunteers matched for age and gender with no previous psychiatric history received either citalopram (SSRI; selective serotonergic reuptake inhibitor), reboxetine (SNRI; selective noradrenergic reuptake inhibitor) or placebo for 7 days in a double-blind design. Using resting-state functional magnetic resonance imaging and seed based connectivity analysis we selected the right nucleus accumbens, the right amygdala, the subgenual cingulate and the dorsal medial prefrontal cortex as seed regions. Mood and subjective experience were also measured before and after drug administration using self-report scales. Despite no differences in mood across the three groups, we found reduced connectivity between the amygdala and the ventral medial prefrontal cortex in the citalopram group and the amygdala and the orbitofrontal cortex for the reboxetine group. We also found reduced striatal-orbitofrontal cortex connectivity in the reboxetine group. These data suggest that antidepressant medications can decrease resting-state functional connectivity independent of mood change and in areas known to mediate reward and emotional processing in the brain. We conclude that hypothesis-driven seed based analysis of resting-state fMRI supports the proposition that antidepressant medications might work by normalising the elevated resting-state functional connectivity seen in depressed patients.NeuroImage 05/2011; 57(4):1317-23. · 5.89 Impact Factor -
Article: The D2 antagonist sulpiride modulates the neural processing of both rewarding and aversive stimuli in healthy volunteers.
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ABSTRACT: Animal studies indicate that dopamine pathways in the ventral striatum code for the motivational salience of both rewarding and aversive stimuli, but evidence for this mechanism in humans is less established. We have developed a functional magnetic resonance imaging (fMRI) model which permits examination of the neural processing of both rewarding and aversive stimuli. The aim of the study was to determine the effect of the dopamine receptor antagonist, sulpiride, on the neural processing of rewarding and aversive stimuli in healthy volunteers. We studied 30 healthy participants who were randomly allocated to receive a single dose of sulpiride (400 mg) or placebo, in a double-blind, parallel-group design. We used fMRI to measure the neural response to rewarding (taste or sight of chocolate) and aversive stimuli (sight of mouldy strawberries or unpleasant strawberry taste) 4 h after drug treatment. Relative to placebo, sulpiride reduced blood oxygenation level-dependent responses to chocolate stimuli in the striatum (ventral striatum) and anterior cingulate cortex. Sulpiride also reduced lateral orbitofrontal cortex and insula activations to the taste and sight of the aversive condition. These results suggest that acute dopamine receptor blockade modulates mesolimbic and mesocortical neural activations in response to both rewarding and aversive stimuli in healthy volunteers. This effect may be relevant to the effects of dopamine receptor antagonists in the treatment of psychosis and may also have implications for the possible antidepressant properties of sulpiride.Psychopharmacologia 04/2011; 217(2):271-8. · 4.08 Impact Factor -
Article: Serotonergic activity influences the cognitive appraisal of close intimate relationships in healthy adults.
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ABSTRACT: Close supportive relationships protect against psychological disorders and also facilitate recovery. However, little is known about the neurochemical mechanisms that mediate these effects. Variation in serotonin function influences affiliative behavior in humans and nonhuman primates. Here, we used tryptophan depletion in healthy adults to investigate the role of serotonin in the cognitive appraisal of close personal relationships. Twenty-two healthy adults drank an amino acid drink without tryptophan, and 19 healthy adults drank an amino acid drink containing tryptophan. Participants were presented with color photographs of heterosexual "couples" standing apart or making affiliative touch gestures and rated the couples for descriptors that capture qualities of close personal relationships. Trait attachment style and state affect of participants were also measured. Tryptophan depletion reduced the judged intimacy and romance of photographed couples. Tryptophan-depleted women rated men as more dominant in relationships and touching couples as more able to resolve their conflicts, when compared with nondepleted women. These effects were not due to changes in mood and remained statistically reliable when the marked impact of attachment style upon relationship judgments was statistically controlled. Our results suggest that central serotonin activity influences the appraisal of close intimate partnerships, raising the possibility that serotonergic dysfunction contributes to altered cognitions about relationships in psychiatric illnesses.Biological psychiatry 03/2011; 69(8):720-5. · 8.93 Impact Factor -
Article: Reduced neural response to reward following 7 days treatment with the cannabinoid CB1 antagonist rimonabant in healthy volunteers.
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ABSTRACT: Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. The anti-obesity drug and cannabinoid type 1 receptor (CB(1)) antagonist, rimonabant, is associated with significant rates of depression and anxiety in clinical use and was recently withdrawn from the market because of these adverse effects. Using a functional magnetic resonance imaging (fMRI) model of reward we hypothesized that rimonabant would impair reward processing. Twenty-two healthy participants were randomly allocated to receive rimonabant (20 mg), or placebo, for 7 d in a double-blind, parallel group design. We used fMRI to measure the neural response to rewarding (sight and/or flavour of chocolate) and aversive (sight of mouldy strawberries and/or an unpleasant strawberry taste) stimuli on the final day of drug treatment. Rimonabant reduced the neural response to chocolate stimuli in key reward areas such as the ventral striatum and the orbitofrontal cortex. Rimonabant also decreased neural responses to the aversive stimulus condition in the caudate nucleus and ventral striatum, but increased lateral orbitofrontal activations to the aversive sight and taste of strawberry condition. Our findings are the first to show that the anti-obesity drug rimonabant inhibits the neural processing of rewarding food stimuli in humans. This plausibly underlies its ability to promote weight loss, but may also indicate a mechanism for inducing anhedonia which could lead to the increased risk of depressive symptomatology seen in clinical use. fMRI may be a useful method of screening novel agents for unwanted effects on reward and associated clinical adverse reactions.The International Journal of Neuropsychopharmacology 09/2010; 13(8):1103-13. · 4.58 Impact Factor -
Article: Diminished neural processing of aversive and rewarding stimuli during selective serotonin reuptake inhibitor treatment.
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ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are popular medications for anxiety and depression, but their effectiveness, particularly in patients with prominent symptoms of loss of motivation and pleasure, has been questioned. There are few studies of the effect of SSRIs on neural reward mechanisms in humans. We studied 45 healthy participants who were randomly allocated to receive the SSRI citalopram, the noradrenaline reuptake inhibitor reboxetine, or placebo for 7 days in a double-blind, parallel group design. We used functional magnetic resonance imaging to measure the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (sight of moldy strawberries and/or an unpleasant strawberry taste) on the final day of drug treatment. Citalopram reduced activation to the chocolate stimuli in the ventral striatum and the ventral medial/orbitofrontal cortex. In contrast, reboxetine did not suppress ventral striatal activity and in fact increased neural responses within medial orbitofrontal cortex to reward. Citalopram also decreased neural responses to the aversive stimuli conditions in key "punishment" areas such as the lateral orbitofrontal cortex. Reboxetine produced a similar, although weaker effect. Our findings are the first to show that treatment with SSRIs can diminish the neural processing of both rewarding and aversive stimuli. The ability of SSRIs to decrease neural responses to reward might underlie the questioned efficacy of SSRIs in depressive conditions characterized by decreased motivation and anhedonia and could also account for the experience of emotional blunting described by some patients during SSRI treatment.Biological psychiatry 03/2010; 67(5):439-45. · 8.93 Impact Factor -
Article: NK1 receptor antagonism and the neural processing of emotional information in healthy volunteers.
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ABSTRACT: The neuropeptide substance P and its receptor NK1 have been implicated in emotion, anxiety and stress in preclinical studies. However, the role of NK1 receptors in human brain function is less clear and there have been inconsistent reports of the value of NK1 receptor antagonists in the treatment of clinical depression. The present study therefore aimed to investigate effects of NK1 antagonism on the neural processing of emotional information in healthy volunteers. Twenty-four participants were randomized to receive a single dose of aprepitant (125 mg) or placebo. Approximately 4 h later, neural responses during facial expression processing and an emotional counting Stroop word task were assessed using fMRI. Mood and subjective experience were also measured using self-report scales. As expected a single dose of aprepitant did not affect mood and subjective state in the healthy volunteers. However, NK1 antagonism increased responses specifically during the presentation of happy facial expressions in both the rostral anterior cingulate and the right amygdala. In the emotional counting Stroop task the aprepitant group had increased activation in both the medial orbitofrontal cortex and the precuneus cortex to positive vs. neutral words. These results suggest consistent effects of NK1 antagonism on neural responses to positive affective information in two different paradigms. Such findings confirm animal studies which support a role for NK1 receptors in emotion. Such an approach may be useful in understanding the effects of novel drug treatments prior to full-scale clinical trials.The International Journal of Neuropsychopharmacology 07/2009; 12(9):1261-74. · 4.58 Impact Factor -
Article: Neural representation of reward in recovered depressed patients.
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ABSTRACT: Anhedonia, a loss of interest and pleasure in normally rewarding stimuli, is a key diagnostic criterion for major depression. It has been suggested that deficits in the processing of reward-relevant stimuli could represent an endophenotype for depression. We hypothesized that people at risk of depression by virtue of a personal history of the illness would show impaired neural responses to a primary rewarding stimulus. Using functional magnetic resonance imaging, we measured the neural response to the sight and flavor of chocolate, and their combination, in 13 unmedicated recovered patients with a history of major depression and 14 healthy controls matched for age and gender. We also examined a control aversive condition consisting of the sight of moldy strawberries and a corresponding unpleasant taste. Participants simultaneously recorded subjective ratings of "pleasantness," "intensity," and "wanting." Despite no differences between the groups in stimulus ratings, patients showed decreased neural responses to the pleasant stimulus in the ventral striatum and increases in the caudate nucleus to the aversive stimulus. Furthermore, patients had a diminished neural supralinearity response (the potentiation produced by simultaneous presentation of the sight and flavor of the stimuli) in the prefrontal cortex for both aversive and pleasant conditions. Patients recovered from depression appear to have deficits in the neural basis of reward and may also have impairments in the cross-modal integration of sensory stimuli. These findings support the view that abnormal neural responses to reward may be an endophenotype for depression and a potential target for intervention and prevention strategies.Psychopharmacologia 07/2009; 205(4):667-77. · 4.08 Impact Factor -
Article: Cognitive influences on the affective representation of touch and the sight of touch in the human brain.
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ABSTRACT: We show that the affective experience of touch and the sight of touch can be modulated by cognition, and investigate in an fMRI study where top-down cognitive modulations of bottom-up somatosensory and visual processing of touch and its affective value occur in the human brain. The cognitive modulation was produced by word labels, 'Rich moisturizing cream' or 'Basic cream', while cream was being applied to the forearm, or was seen being applied to a forearm. The subjective pleasantness and richness were modulated by the word labels, as were the fMRI activations to touch in parietal cortex area 7, the insula and ventral striatum. The cognitive labels influenced the activations to the sight of touch and also the correlations with pleasantness in the pregenual cingulate/orbitofrontal cortex and ventral striatum. Further evidence of how the orbitofrontal cortex is involved in affective aspects of touch was that touch to the forearm [which has C fiber Touch (CT) afferents sensitive to light touch] compared with touch to the glabrous skin of the hand (which does not) revealed activation in the mid-orbitofrontal cortex. This is of interest as previous studies have suggested that the CT system is important in affiliative caress-like touch between individuals.Social Cognitive and Affective Neuroscience 07/2008; 3(2):97-108. · 6.13 Impact Factor -
Article: Expected value, reward outcome, and temporal difference error representations in a probabilistic decision task.
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ABSTRACT: In probabilistic decision tasks, an expected value (EV) of a choice is calculated, and after the choice has been made, this can be updated based on a temporal difference (TD) prediction error between the EV and the reward magnitude (RM) obtained. The EV is measured as the probability of obtaining a reward x RM. To understand the contribution of different brain areas to these decision-making processes, functional magnetic resonance imaging activations related to EV versus RM (or outcome) were measured in a probabilistic decision task. Activations in the medial orbitofrontal cortex were correlated with both RM and with EV and confirmed in a conjunction analysis to extend toward the pregenual cingulate cortex. From these representations, TD reward prediction errors could be produced. Activations in areas that receive from the orbitofrontal cortex including the ventral striatum, midbrain, and inferior frontal gyrus were correlated with the TD error. Activations in the anterior insula were correlated negatively with EV, occurring when low reward outcomes were expected, and also with the uncertainty of the reward, implicating this region in basic and crucial decision-making parameters, low expected outcomes, and uncertainty.Cerebral Cortex 04/2008; 18(3):652-63. · 6.54 Impact Factor -
Article: Enhanced affective brain representations of chocolate in cravers vs. non-cravers.
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ABSTRACT: To examine the neural circuitry involved in food craving, in making food particularly appetitive and thus in driving wanting and eating, we used fMRI to measure the response to the flavour of chocolate, the sight of chocolate and their combination in cravers vs. non-cravers. Statistical parametric mapping (SPM) analyses showed that the sight of chocolate produced more activation in chocolate cravers than non-cravers in the medial orbitofrontal cortex and ventral striatum. For cravers vs. non-cravers, a combination of a picture of chocolate with chocolate in the mouth produced a greater effect than the sum of the components (i.e. supralinearity) in the medial orbitofrontal cortex and pregenual cingulate cortex. Furthermore, the pleasantness ratings of the chocolate and chocolate-related stimuli had higher positive correlations with the fMRI blood oxygenation level-dependent signals in the pregenual cingulate cortex and medial orbitofrontal cortex in the cravers than in the non-cravers. To our knowledge, this is the first study to show that there are differences between cravers and non-cravers in their responses to the sensory components of a craved food in the orbitofrontal cortex, ventral striatum and pregenual cingulate cortex, and that in some of these regions the differences are related to the subjective pleasantness of the craved foods. Understanding individual differences in brain responses to very pleasant foods helps in the understanding of the mechanisms that drive the liking for specific foods and thus intake of those foods.European Journal of Neuroscience 09/2007; 26(4):1067-76. · 3.63 Impact Factor -
Article: Umami: a delicious flavor formed by convergence of taste and olfactory pathways in the human brain.
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ABSTRACT: Umami taste is produced by glutamate acting on a fifth taste system. However, glutamate presented alone as a taste stimulus is not highly pleasant, and does not act synergistically with other tastes (sweet, salt, bitter and sour). We show here that when glutamate is given in combination with a consonant, savory, odour (vegetable), the resulting flavor can be much more pleasant. Moreover, we showed using functional brain imaging with fMRI that the glutamate taste and savory odour combination produced much greater activation of the medial orbitofrontal cortex and pregenual cingulate cortex than the sum of the activations by the taste and olfactory components presented separately. Supralinear effects were much less (and significantly less) evident for sodium chloride and vegetable odour. Further, activations in these brain regions were correlated with the pleasantness and fullness of the flavor, and with the consonance of the taste and olfactory components. Supralinear effects of glutamate taste and savory odour were not found in the insular primary taste cortex. We thus propose that glutamate acts by the nonlinear effects it can produce when combined with a consonant odour in multimodal cortical taste-olfactory convergence regions. We propose the concept that umami can be thought of as a rich and delicious flavor that is produced by a combination of glutamate taste and a consonant savory odour. Glutamate is thus a flavor enhancer because of the way that it can combine supralinearly with consonant odours in cortical areas where the taste and olfactory pathways converge far beyond the receptors.European Journal of Neuroscience 04/2007; 25(6):1855-64. · 3.63 Impact Factor
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2007–2013
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University of Oxford
- • Department of Psychiatry
- • Department of Experimental Psychology
Oxford, ENG, United Kingdom
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