Biomedical subjects

Andrew D Lawrence

Publications and source records attributed to Andrew D Lawrence.

At least 19 recordsLinked to original sources

PubMed2006

Heartbeat perception in depression.

Alterations in bodily awareness have been implicated in depression but there has been little detailed empirical characterisation of the degree and accuracy of body perception in the disorder. The present study examined the objective accuracy of heartbeat perception (using the Schandry mental tracking task) and the subjective degree of bodily focus (using the Bodily Consciousness Questionnaire; BCQ) in healthy control volunteers, a moderately depressed community sample, and a more severely depressed clinic sample (n=18 in each group). The community sample showed less accurate heartbeat perception than the control group as expected. Counter to prediction, however, the more severely depressed clinic sample performed better than the community depressed sample and equivalently to control volunteers on the Schandry task. There were no group differences on subjective bodily awareness. Implications for theories of depression are discussed.

Adult↗

PubMed2006

Neural processing of fearful faces: effects of anxiety are gated by perceptual capacity limitations.

Debate continues as to the automaticity of the amygdala's response to threat. Accounts taking a strong automaticity line suggest that the amygdala's response to threat is both involuntary and independent of attentional resources. Building on these accounts, prominent models have suggested that anxiety modulates the output of an amygdala-based preattentive threat evaluation system. Here, we argue for a modification of these models. Functional magnetic resonance imaging data were collected while volunteers performed a letter search task of high or low perceptual load superimposed on fearful or neutral face distractors. Neither high- nor low-anxious volunteers showed an increased amygdala response to threat distractors under high perceptual load, contrary to a strong automaticity account of amygdala function. Under low perceptual load, elevated state anxiety was associated with a heightened response to threat distractors in the amygdala and superior temporal sulcus, whereas individuals high in trait anxiety showed a reduced prefrontal response to these stimuli, consistent with weakened recruitment of control mechanisms used to prevent the further processing of salient distractors. These findings suggest that anxiety modulates processing subsequent to competition for perceptual processing resources, with state and trait anxiety having distinguishable influences upon the neural mechanisms underlying threat evaluation and "top-down" control.

Adolescent↗

PubMed2006

Impaired recognition of facial expressions of anger in Parkinson's disease patients acutely withdrawn from dopamine replacement therapy.

We have previously reported that acute dopaminergic blockade in healthy volunteers results in a transient disruption of the recognition of facial expressions of anger, whilst leaving intact the recognition of other facial expressions (including fear and disgust) and facial identity processing. Parkinson's disease (PD) is characterised by cell loss in dopaminergic neuronal populations, and hence we predicted that PD would be associated with impaired anger recognition. We reasoned that treatment with dopamine replacement therapy (DRT) could mask any deficit present in PD, and therefore studied facial expression recognition in a group of PD patients transiently withdrawn from DRT. Seventeen PD patients were compared to 21 age- and IQ-matched controls on the Ekman 60 task, which required the forced-choice labelling of 10 exemplars of each of six facial expressions (anger, disgust, fear, sadness, happiness, surprise). In line with our predictions, PD patients showed a selective impairment in the recognition of facial expressions of anger. This deficit was not related to the PD patients' performance on the Benton unfamiliar-face matching task, which was normal, nor was the deficit related to overall disease severity, or to depression symptoms. However, as predicted by simulation theories, impaired anger recognition in PD was related to reduced levels of the anger-linked temperament trait, exploratory excitability. The results extend our previous findings of a role for dopamine in the processing of facial expressions of anger, and demonstrate the power of adopting a phylogenetic, comparative perspective on emotions.

Aged↗

PubMed2006

Individual differences in reward drive predict neural responses to images of food.

A network of interconnected brain regions, including orbitofrontal, ventral striatal, amygdala, and midbrain areas, has been widely implicated in a number of aspects of food reward. However, in humans, sensitivity to reward can vary significantly from one person to the next. Individuals high in this trait experience more frequent and intense food cravings and are more likely to be overweight or develop eating disorders associated with excessive food intake. Using functional magnetic resonance imaging, we report that individual variation in trait reward sensitivity (as measured by the Behavioral Activation Scale) is highly correlated with activation to images of appetizing foods (e.g., chocolate cake, pizza) in a fronto-striatal-amygdala-midbrain network. Our findings demonstrate that there is considerable personality-linked variability in the neural response to food cues in healthy participants and provide important insight into the neurobiological factors underlying vulnerability to certain eating problems (e.g., hyperphagic obesity).

Adult↗

PubMed2006

Compulsive drug use linked to sensitized ventral striatal dopamine transmission.

OBJECTIVE: A small group of Parkinson's disease (PD) patients compulsively use dopaminergic drugs despite causing harmful social, psychological, and physical effects and fulfil core Diagnostic and Statistical Manual (of Mental Disorders) Fourth Edition criteria for substance dependence (dopamine dysregulation syndrome [DDS]). We aimed to evaluate levodopa-induced dopamine neurotransmission in the striatum of patients with DDS compared with PD control patients. METHODS: We used a two-scan positron emission tomography protocol to calculate the percentage change in (11)C-raclopride binding potential from a baseline withdrawal (off drug) state to the binding potential after an oral dose of levodopa. We related the subjective effects of levodopa to the effects on endogenous dopamine release of a pharmacological challenge with levodopa in eight control PD patients and eight patients with DDS. RESULTS: PD patients with DDS exhibited enhanced levodopa-induced ventral striatal dopamine release compared with levodopa-treated patients with PD not compulsively taking dopaminergic drugs. The sensitized ventral striatal dopamine neurotransmission produced by levodopa in these individuals correlated with self-reported compulsive drug "wanting" but not "liking" and was related to heightened psychomotor activation (punding). INTERPRETATION: This provides evidence that links sensitization of ventral striatal circuitry in humans to compulsive drug use.

Aged↗

PubMed2005

Algae acquire vitamin B12 through a symbiotic relationship with bacteria.

Vitamin B12 (cobalamin) was identified nearly 80 years ago as the anti-pernicious anaemia factor in liver, and its importance in human health and disease has resulted in much work on its uptake, cellular transport and utilization. Plants do not contain cobalamin because they have no cobalamin-dependent enzymes. Deficiencies are therefore common in strict vegetarians, and in the elderly, who are susceptible to an autoimmune disorder that prevents its efficient uptake. In contrast, many algae are rich in vitamin B12, with some species, such as Porphyra yezoensis (Nori), containing as much cobalamin as liver. Despite this, the role of the cofactor in algal metabolism remains unknown, as does the source of the vitamin for these organisms. A survey of 326 algal species revealed that 171 species require exogenous vitamin B12 for growth, implying that more than half of the algal kingdom are cobalamin auxotrophs. Here we show that the role of vitamin B12 in algal metabolism is primarily as a cofactor for vitamin B12-dependent methionine synthase, and that cobalamin auxotrophy has arisen numerous times throughout evolution, probably owing to the loss of the vitamin B12-independent form of the enzyme. The source of cobalamin seems to be bacteria, indicating an important and unsuspected symbiosis.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2005

The somatic marker hypothesis: a critical evaluation.

The somatic marker hypothesis (SMH; [Damasio, A. R., Tranel, D., Damasio, H., 1991. Somatic markers and the guidance of behaviour: theory and preliminary testing. In Levin, H.S., Eisenberg, H.M., Benton, A.L. (Eds.), Frontal Lobe Function and Dysfunction. Oxford University Press, New York, pp. 217-229]) proposes that emotion-based biasing signals arising from the body are integrated in higher brain regions, in particular the ventromedial prefrontal cortex (VMPFC), to regulate decision-making in situations of complexity. Evidence for the SMH is largely based on performance on the Iowa Gambling Task (IGT; [Bechara, A., Tranel, D., Damasio, H., Damasio, A.R., 1996. Failure to respond autonomically to anticipated future outcomes following damage to prefrontal cortex. Cerebral Cortex 6 (2), 215-225]), linking anticipatory skin conductance responses (SCRs) to successful performance on a decision-making paradigm in healthy participants. These 'marker' signals were absent in patients with VMPFC lesions and were associated with poorer IGT performance. The current article reviews the IGT findings, arguing that their interpretation is undermined by the cognitive penetrability of the reward/punishment schedule, ambiguity surrounding interpretation of the psychophysiological data, and a shortage of causal evidence linking peripheral feedback to IGT performance. Further, there are other well-specified and parsimonious explanations that can equally well account for the IGT data. Next, lesion, neuroimaging, and psychopharmacology data evaluating the proposed neural substrate underpinning the SMH are reviewed. Finally, conceptual reservations about the novelty, parsimony and specification of the SMH are raised. It is concluded that while presenting an elegant theory of how emotion influences decision-making, the SMH requires additional empirical support to remain tenable.

Adaptation, Psychological↗

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↗

PubMed2004

State anxiety modulation of the amygdala response to unattended threat-related stimuli.

Findings from fear-conditioning studies in rats and functional neuroimaging with human volunteers have led to the suggestion that the amygdala is involved in the preattentive detection of threat-related stimuli. However, some neuroimaging findings point to attentional modulation of the amygdala response. The clinical-cognitive literature suggests that the extent to which the processing of threat-related stimuli is modulated by attention is crucially dependent on participants' anxiety levels. Here, we conducted a functional magnetic resonance imaging study with 27 healthy volunteers to examine whether amygdala responsivity to unattended threat-related stimuli varies with individual differences in state anxiety. Pairs of houses and faces (both fearful or neutral in expression) were presented, and participants attended to either the faces or the houses and matched these stimuli on identity. "Low-anxious" participants showed a reduced amygdala response to unattended versus attended fearful faces, but "high-anxious" participants showed no such reduction, having an increased amygdala response to fearful versus neutral faces regardless of attentional focus. These findings suggest that anxiety may interact with attentional focus to determine the magnitude of the amygdala response to threat-related stimuli.

Adolescent↗

PubMed2004

Identification and characterization of a novel vitamin B12 (cobalamin) biosynthetic enzyme (CobZ) from Rhodobacter capsulatus, containing flavin, heme, and Fe-S cofactors.

One of the most intriguing steps during cobalamin (vitamin B12) biosynthesis is the ring contraction process that leads to the extrusion of one of the integral macrocyclic carbon atoms from the tetrapyrrole-derived framework. The aerobic cobalamin pathway requires the action of a monooxygenase called CobG (precorrin-3B synthase), which generates a hydroxylactone intermediate that is subsequently ring-contracted by CobJ. However, in the photosynthetic bacterium Rhodobacter capsulatus, which harbors an aerobic-like pathway, there is no cobG in the main cobalamin biosynthetic operon although it does contain an additional uncharacterized gene called orf663. To demonstrate the involvement of Orf663 in cobalamin synthesis, the first dedicated 10 genes of the B12 pathway (including orf663), encoding enzymes for the transformation of uroporphyrinogen III into hydrogenobyrinic acid (HBA), were sequentially cloned into a plasmid to generate an artificial operon, which, when transformed into Escherichia coli, endowed the host with the ability to make HBA. Deletion of orf663 from this operon prevented HBA synthesis, demonstrating that it was essential for corrin construction. HBA synthesis was restored to this recombinant strain either by returning orf663 or by substituting it with cobG. Recombinant overproduction of Orf663, now renamed CobZ, allowed the characterization of a novel cofactor-rich protein, housing two Fe-S centers, a flavin, and a heme group, which like B12 itself is a modified tetrapyrrole. A mechanism for Orf663 (CobZ) in cobalamin biosynthesis is proposed.

Bacterial Proteins↗

PubMed2004

Impaired recognition of anger following damage to the ventral striatum.

Comparative neuropsychology has identified a role for the ventral striatum (VS) in certain forms of aggression. To address whether the homologous region in humans also contributes to the emotion anger, we studied a case series of four human subjects with focal lesions affecting the VS. All four demonstrated a disproportionate impairment in recognizing human signals of aggression. By contrast, a control group of individuals with damage to more dorsal basal ganglia (BG) regions showed no evidence of an anger impairment. Our findings demonstrate that the VS makes a significant contribution to coding signals of aggression in humans, and emphasize the importance of an approach to human affective neuroscience based on cross-species homologies. The results are discussed in relation to the ventral striatal dopamine system's role in the pursuit of biological resources in general. We propose that the role of the VS in the recognition of human signals of anger may reflect a more general role in the coordination of behaviour relevant to the acquisition and protection of valued resources, including detection of signals of conspecific challenge (anger).

Adult↗

PubMed2004

Prefrontal cortical function and anxiety: controlling attention to threat-related stimuli.

Threat-related stimuli are strong competitors for attention, particularly in anxious individuals. We used functional magnetic resonance imaging (fMRI) with healthy human volunteers to study how the processing of threat-related distractors is controlled and whether this alters as anxiety levels increase. Our work builds upon prior analyses of the cognitive control functions of lateral prefrontal cortex (lateral PFC) and anterior cingulate cortex (ACC). We found that rostral ACC was strongly activated by infrequent threat-related distractors, consistent with a role for this area in responding to unexpected processing conflict caused by salient emotional stimuli. Participants with higher anxiety levels showed both less rostral ACC activity overall and reduced recruitment of lateral PFC as expectancy of threat-related distractors was established. This supports the proposal that anxiety is associated with reduced top-down control over threat-related distractors. Our results suggest distinct roles for rostral ACC and lateral PFC in governing the processing of task-irrelevant, threat-related stimuli, and indicate reduced recruitment of this circuitry in anxiety.

Adolescent↗

PubMed2004

Presynaptic dopaminergic dysfunction in schizophrenia: a positron emission tomographic [18F]fluorodopa study.

CONTEXT: The dopamine overactivity hypothesis of schizophrenia remains one of the most influential theories of the pathophysiology of the illness. Radiotracer brain imaging studies are now directly testing aspects of the overactivity hypothesis. OBJECTIVE: To assess presynaptic dopaminergic function in a large cohort of patients with schizophrenia by means of [18F]fluorodopa uptake and a high-sensitivity 3-dimensional positron emission tomograph. We predicted elevations in striatal [18F]fluorodopa uptake and reductions in prefrontal cortical [18F]fluorodopa uptake in patients with schizophrenia. DESIGN: Case-control study. SETTING: Research institute investigation recruiting hospital outpatients. PATIENTS: Sixteen male medicated hospital outpatients with a DSM-IV diagnosis of schizophrenia (mean age, 38 years) and 12 age-matched male volunteers free of psychiatric and neurologic illness. INTERVENTION: [18F]fluorodopa positron emission tomographic scanning. MAIN OUTDOME MEASURE: [18F]fluorodopa uptake constant Ki measured with statistical parametric mapping and region-of-interest analyses. RESULTS: Statistical parametric mapping (P<.05 corrected) and region-of-interest analyses (P<.01) showed increased [18F]fluorodopa uptake, confined primarily to the ventral striatum in patients with schizophrenia. No reductions in prefrontal cortical [18F]fluorodopa uptake Ki were seen in the statistical parametric mapping and region-of-interest analyses, although dorsal anterior cingulate [18F]fluorodopa Ki correlated with performance on the Stroop Color-Word Test in both groups. CONCLUSIONS: As in studies in unmedicated patients, presynaptic striatal dopamine dysfunction is present in medicated schizophrenic patients, adding further in vivo support for dopamine overactivity in the illness.

Adult↗

PubMed2004

Punding in Parkinson's disease: its relation to the dopamine dysregulation syndrome.

Punding is a term that was coined originally to describe complex prolonged, purposeless, and stereotyped behaviour in chronic amphetamine users. A structured interview of 50 patients with higher dopamine replacement therapy requirements (>800 levodopa equivalent units/day) from 123 unselected patients with Parkinson's disease (PD) from a PD clinic identified 17 (14%) patients with punding. Punding was acknowledged as disruptive and unproductive by the patients themselves, but forcible attempts by family to interrupt the behaviour led to irritability and dysphoria. Punding was associated with very high doses of dopamine replacement therapy often related to a pattern of chronic inappropriate overuse of dopaminergic medication. We believe that this is an underreported, socially disabling phenomenon that is commonly associated with the syndrome of dopamine dysregulation and is phenomenologically distinct from both obsessive-compulsive disorder and mania.

Aged↗

PubMed2004

Categorical and dimensional reports of experienced affect to emotion-inducing pictures in depression.

Self-reported affect to positive and negative emotional pictures was contrasted in people with major depressive disorder (MDD) and never-depressed control participants (n = 25 in each group). The results revealed significant differences in response to positive images (reduced arousal, less pleasant valence, decreased happiness, increased sadness) in MDD but no clear group differences in response to negative stimuli. Extending earlier findings of reduced responsiveness to positive, but not negative, stimuli in MDD (D. M. Sloan, M. E. Strauss, S. W. Quirk, & M. Satajovik, 1997; D. M. Sloan, M. E. Strauss, & K. L. Wisner, 2001), the data indicate that blunted response to positive stimuli is found when both categorical and dimensional ratings are elicited. Further, the data replicate earlier findings of elevated sadness reports to positive stimuli (J. Rottenberg, K. L. Kasch, J. J. Gross, & I. H. Gotlib, 2002), which may reflect broader difficulties in regulating emotions in MDD.

Affect↗

PubMed2004

Reward processing in health and Parkinson's disease: neural organization and reorganization.

It has been suggested that motivational processes mediated by dopaminergic neural systems may be relatively spared in Parkinson's disease (PD) and activation of these pathways may be of therapeutic relevance. To investigate the behavioural and neural correlates of motivation in unmedicated PD patients, we used H(2)(15)O positron emission tomography to measure brain activation patterns related to the processing of monetary rewards of different magnitudes during a spatial search task in PD patients withdrawn from medication, and age-matched healthy controls. Both groups showed increased search efficiency with increasing reward, but demonstrated different patterns of neuronal activation. In healthy controls activity in prefrontal and rhinal cortices, and thalamic activity correlated with reward magnitude. In contrast, activity in the cerebellar vermis in PD patients increased with increasing reward magnitude, suggesting it was sensitive to motivational state. We interpret these relative increases in cerebellar activation as evidence for the presence of compensatory neural mechanisms in unmedicated PD patients.

Aged↗

PubMed2004

Individual differences in the modulation of fear-related brain activation by attentional control.

In this article, we consider the extent to which variations in the neural activation associated with fear-related stimuli are obligatory or optional. More specifically, we investigated modulation of activation according to type of encoding operation, and how this relates to individual differences in fearfulness and attentional control. In an fMRI study, fear-related (relative to neutral) pictures preferentially activated many of the regions involved in a hierarchical system responsible for organizing defensive behavior, and differential activation in some of these areas was related to self-reported individual variations in fearfulness. Preferential activation according to type of stimulus persisted to a limited extent even when attention was diverted from its emotional aspects. Importantly, however, encoding tasks involving attention to emotional versus nonemotional attributes of the same pictures revealed a pattern of greater activation during emotional encoding, similar to that differentiating fear-related from neutral stimuli. Again, the degree of modulation varied according to individual differences. We conclude that fear-related pictures can recruit activation in the defensive system even when attention is directed elsewhere, but that the extent of this activation is modulated by attentional control mechanisms. More critically, both differential activation and its modulation by attentional control are related to individual variations in emotional vulnerability, in a manner that conforms to predictions derived from existing theoretical accounts.

Attention↗

PubMed2003

Systemic sulpiride modulates striatal blood flow: relationships to spatial working memory and planning.

The dopamine D2 receptor antagonist sulpiride can produce a range of cognitive deficits in normal volunteers, consistent with those seen in Parkinson's disease (PD). This, together with studies in experimental animals, implies sulpiride might be acting in the striatum. However, subtle changes in prefrontal cortex (PFC) activity are seen following L-Dopa withdrawal in PD during working memory tasks, suggesting that this may be a further site of action for dopamine D2 receptor antagonists. We have investigated the effects of sulpiride within the PFC and striatum in normal male volunteers. In two separate experiments, using identical PET regional cerebral blood flow (rCBF) methods, a combined drug and psychological challenge was performed, utilising working memory and planning tasks, and oral sulpiride 400 mg and placebo. Data were analysed using SPM99. Sulpiride increased striatal rCBF bilaterally and the working memory and planning tasks activated discrete frontoparietal networks in keeping with previous studies. However, for the working memory tasks, no changes in performance or task-induced rCBF were observed after sulpiride. For the planning task, improved performance was seen on sulpiride. Also, sulpiride attenuated striatal activity during planning (as assessed using a small volume correction, P<0.05 corrected), and this attenuation was related to performance changes. These findings suggest that (1) sulpiride produces clear increases in striatal rCBF, (2) in contrast to previous studies no effects of sulpiride on performance of the working memory tasks or the associated neural networks were observed, and (3) sulpiride may modulate performance of more complex cognitive tasks via alterations in striatal neural activity.

Adult↗