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  • Journal article
    Hampshire A, Thompson R, Duncan J, Owen AMet al., 2008,

    The target selective neural response--similarity, ambiguity, and learning effects

    , PLoS One, Vol: 3, ISSN: 1932-6203

    A network of frontal and parietal brain regions is commonly recruited during tasks that require the deliberate 'top-down' control of thought and action. Previously, using simple target detection, we have demonstrated that within this frontoparietal network, the right ventrolateral prefrontal cortex (VLPFC) in particular is sensitive to the presentation of target objects. Here, we use a range of target/non-target morphs to plot the target selective response within distinct frontoparietal sub-regions in greater detail. The increased resolution allows us to examine the extent to which different cognitive factors can predict the blood oxygenation level dependent (BOLD) response to targets. Our results reveal that both probability of positive identification (similarity to target) and proximity to the 50% decision boundary (ambiguity) are significant predictors of BOLD signal change, particularly in the right VLPFC. Furthermore, the profile of target related signal change is not static, with the degree of selectivity increasing as the task becomes familiar. These findings demonstrate that frontoparietal sub-regions are recruited under increased cognitive demand and that when recruited, they adapt, using both fast and slow mechanisms, to selectively respond to those items that are of the most relevance to current intentions.

  • Journal article
    Chamberlain SR, Menzies L, Hampshire A, Suckling J, Fineberg NA, del Campo N, Aitken M, Craig K, Owen AM, Bullmore ET, Robbins TW, Sahakian BJet al., 2008,

    Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives

    , Science, Vol: 321, Pages: 421-422, ISSN: 1095-9203

    Obsessive-compulsive disorder (OCD) is characterized by repetitive thoughts and behaviors associated with underlying dysregulation of frontostriatal circuitry. Central to neurobiological models of OCD is the orbitofrontal cortex, a neural region that facilitates behavioral flexibility after negative feedback (reversal learning). We identified abnormally reduced activation of several cortical regions, including the lateral orbitofrontal cortex, during reversal learning in OCD patients and their clinically unaffected close relatives, supporting the existence of an underlying previously undiscovered endophenotype for this disorder.

  • Journal article
    Hampshire A, Gruszka A, Fallon SJ, Owen AMet al., 2008,

    Inefficiency in self-organized attentional switching in the normal aging population is associated with decreased activity in the ventrolateral prefrontal cortex

    , J Cogn Neurosci, Vol: 20, Pages: 1670-1686, ISSN: 0898-929X

    Studies of the aging brain have demonstrated that areas of the frontal cortex, along with their associated top-down executive control processes, are particularly prone to the neurodegenerative effects of age. Here, we investigate the effects of aging on brain and behavior using a novel task, which allows us to examine separate components of an individual's chosen strategy during routine problem solving. Our findings reveal that, contrary to previous suggestions of a specific decrease in cognitive flexibility, older participants show no increased level of perseveration to either the recently rewarded object or the recently relevant object category. In line with this lack of perseveration, lateral and medial regions of the orbito-frontal cortex, which are associated with inhibitory control and reward processing, appear to be functionally intact. Instead, a general loss of efficient problem-solving strategy is apparent with a concomitant decrease in neural activity in the ventrolateral prefrontal cortex and the posterior parietal cortex. The dorsolateral prefrontal cortex is also affected during problem solving, but age-related decline within this region appears to occur at a later stage.

  • Journal article
    Williams-Gray CH, Hampshire A, Barker RA, Owen AMet al., 2008,

    Attentional control in Parkinson's disease is dependent on COMT val 158 met genotype

    , Brain, Vol: 131, Pages: 397-408, ISSN: 1460-2156

    Cognitive deficits occur even in the earliest stages of Parkinson's disease. Some such deficits are known to relate to dysfunction in dopaminergic frontostriatal networks, and may be influenced by a common functional polymorphism (val(158)met) within the catechol O-methyltransferase (COMT) gene. Abnormal attentional shifting behaviour is an important and well-recognized cognitive problem in PD, but nonetheless its precise cognitive and neural basis remains unclear. Here we explored this impairment in an fMRI study employing a recently developed cognitive task designed to fractionate components of attentional control. We investigated the impact of the COMT val(158)met genotype and dopaminergic medication on both patterns of behaviour and associated brain activation in 29 medicated patients with early PD. Genotype had a critical impact on task strategy: whilst patients with high activity COMT genotypes (val/val) adopted a typical approach of preferentially shifting attention within rather than between dimensions, those with low activity genotypes (met/met) failed to adopt such a strategy, suggesting an inability to form an attentional 'set'. Moreover, this behaviour was associated with significant underactivation across the frontoparietal attentional network. Furthermore, we demonstrated an interactive effect of COMT genotype and dopaminergic medication on task performance and BOLD response. Hence we have shown for the first time that attentional control in PD is critically determined by genetic and pharmacological influences on dopaminergic activity in frontoparietal networks. This has important implications for understanding the neurobiological basis of attentional control, and highlights the risk of medication-induced cognitive dysfunction in certain genotypic groups of PD patients, which may ultimately impact on clinical practice.

  • Journal article
    Passamonti L, Rowe JB, Ewbank M, Hampshire A, Keane J, Calder AJet al., 2008,

    Connectivity from the ventral anterior cingulate to the amygdala is modulated by appetitive motivation in response to facial signals of aggression

    , NeuroImage, Vol: 43, Pages: 562-570, ISSN: 1053-8119

    For some people facial expressions of aggression are intimidating, for others they are perceived as provocative, evoking an aggressive response. Identifying the key neurobiological factors that underlie this variation is fundamental to our understanding of aggressive behaviour. The amygdala and the ventral anterior cingulate cortex (ACC) have been implicated in aggression. Using functional magnetic resonance imaging (fMRI), we studied how the interaction between these regions is influenced by the drive to obtain reward (reward-drive or appetitive motivation), a personality trait consistently associated with aggression. Two distinct techniques showed that the connectivity between the ventral ACC and the amygdala was strongly correlated with personality, with high reward-drive participants displaying reduced negative connectivity. Furthermore, the direction of this effect was restricted from ventral ACC to the amygdala but not vice versa. The personality-mediated variation in the pathway from the ventral anterior cingulate cortex to the amygdala provides an account of why signals of aggression are interpreted as provocative by some individuals more than others.

  • Journal article
    Dassan P, Clarke C, Sharp DJ, 2007,

    A Case of Poststreptococcal Opsoclonus-Myoclonus Syndrome

    , Movement Disorders, Vol: 10, Pages: 1490-1491, ISSN: 1531-8257

    High antistreptococcal antibody titer (ASOT) was measured in a 31-year-old Caucasian lady presenting with opsoclonus and myoclonus. She was treated with oral steroids and 8 weeks after the onset of symptoms she had anormal ASOT and only mild residual symptoms. This is one of the first cases of opsoclonus-myoclonus syndrome developing, following a streptococcal infection in adults.

  • Journal article
    Hampshire A, Duncan J, Owen AM, 2007,

    Selective tuning of the blood oxygenation level-dependent response during simple target detection dissociates human frontoparietal subregions

    , J Neurosci, Vol: 27, Pages: 6219-6223, ISSN: 1529-2401

    Current models of working memory and focal attention converge on the idea of an adaptable global system, distributed across a network of frontal and parietal brain regions. Here, we examine how the human frontoparietal network selectively adapts to represent currently relevant information during a simple attentional task: monitoring for a target item in a series of nontargets. Across the entire frontoparietal network, there is selective response to targets, in line with a global system for coding task-relevant inputs. At the same time, there are striking dissociations in response to nontargets; whereas ventrolateral frontal cortex responds just to the target, more dorsal/anterior regions respond to all stimuli from the target category. The results show different degrees of target selectivity across different regions of the frontoparietal network.

  • Journal article
    Boly M, Coleman MR, Davis MH, Hampshire A, Bor D, Moonen G, Maquet PA, Pickard JD, Laureys S, Owen AMet al., 2007,

    When thoughts become action: an fMRI paradigm to study volitional brain activity in non-communicative brain injured patients

    , Neuroimage, Vol: 36, Pages: 979-992, ISSN: 1053-8119

    The assessment of voluntary behavior in non-communicative brain injured patients is often challenging due to the existence of profound motor impairment. In the absence of a full understanding of the neural correlates of consciousness, even a normal activation in response to passive sensory stimulation cannot be considered as proof of the presence of awareness in these patients. In contrast, predicted activation in response to the instruction to perform a mental imagery task would provide evidence of voluntary task-dependent brain activity, and hence of consciousness, in non-communicative patients. However, no data yet exist to indicate which imagery instructions would yield reliable single subject activation. The aim of the present study was to establish such a paradigm in healthy volunteers. Two exploratory experiments evaluated the reproducibility of individual brain activation elicited by four distinct mental imagery tasks. The two most robust mental imagery tasks were found to be spatial navigation and motor imagery. In a third experiment, where these two tasks were directly compared, differentiation of each task from one another and from rest periods was assessed blindly using a priori criteria and was correct for every volunteer. The spatial navigation and motor imagery tasks described here permit the identification of volitional brain activation at the single subject level, without a motor response. Volunteer as well as patient data [Owen, A.M., Coleman, M.R., Boly, M., Davis, M.H., Laureys, S., Pickard J.D., 2006. Detecting awareness in the vegetative state. Science 313, 1402] strongly suggest that this paradigm may provide a method for assessing the presence of volitional brain activity, and thus of consciousness, in non-communicative brain-injured patients.

  • Journal article
    Williams-Gray CH, Hampshire A, Robbins TW, Owen AM, Barker RAet al., 2007,

    Catechol O-methyltransferase Val158Met genotype influences frontoparietal activity during planning in patients with Parkinson's disease

    , J Neurosci, Vol: 27, Pages: 4832-4838, ISSN: 1529-2401

    Cognitive dysfunction commonly occurs even in the early stages of Parkinson's disease (PD). Impairment on frontostriatally based executive tasks is particularly well described but affects only a proportion of early PD patients. Our previous work suggests that a common functional polymorphism (val(158)met) within the catechol O-methyltransferase (COMT) gene underlies some of this executive heterogeneity. In particular, an increasing number of methionine alleles, resulting in lower enzyme activity, is associated with impaired performance on the "Tower of London" planning task. The main objective of this study was to investigate the underlying neural basis of this genotype-phenotype effect in PD using functional magnetic resonance imaging. We scanned 31 patients with early PD who were homozygous for either valine (val) (n = 16) or methionine (met) (n = 15) at the COMT val(158)met polymorphism during performance of an executive task comprising both Tower of London (planning) and simple subtracting ("control") problems. A cross-group comparison between genetic subgroups revealed that response times for planning problems were significantly longer in met compared with val homozygotes, whereas response times for control problems did not differ. Furthermore, imaging data revealed a significant reduction in blood oxygen level-dependent signal across the frontoparietal network involved in planning in met/met compared with val/val patients. Hence, we have demonstrated that COMT genotype impacts on executive function in PD through directly influencing frontoparietal activation. Furthermore, the directionality of the genotype-phenotype effect observed in this study, when interpreted in the context of the existing literature, adds weight to the hypothesis that the relationship between prefrontal function and dopamine levels follows as an inverted U-shaped curve.

  • Journal article
    Sharp DJ, Scott SK, Mehra MA, Wise RJSet al., 2006,

    The neural correlates of declining performance with age: Evidence for age-related changes in cognitive control

    , CEREBRAL CORTEX, Vol: 16, Pages: 1739-1749, ISSN: 1047-3211

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

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