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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
    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
    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
    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
    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
  • Journal article
    Hampshire A, Owen AM, 2006,

    Fractionating attentional control using event-related fMRI

    , Cereb Cortex, Vol: 16, Pages: 1679-1689, ISSN: 1047-3211

    Despite numerous functional neuroimaging and lesion studies of human executive function, the precise neuroanatomical correlates of specific components of attentional control remain controversial. Using a novel approach that focused upon volunteer behavior rather than experimental manipulations, specific components of attentional shifting were fractionated, and their neural correlates differentiated using event-related fMRI. The results demonstrate that the ventrolateral prefrontal cortex is involved in switching attention "between" stimulus dimensions, whereas the posterior parietal cortex mediates changes in stimulus-response mapping. Furthermore, reversals based on negative feedback activated the lateral orbitofrontal cortex, whereas positive feedback modulated activity in the medial orbital frontal cortex. Finally, the dorsolateral prefrontal cortex was active throughout solution search. These findings support the hypothesis that lateral prefrontal, orbital, and parietal areas form a supervisory network that controls the focus of attention and suggests that these regions can be fractionated in terms of their specific contributions.

  • Journal article
    Sharp DJ, Scott SK, Cutler A, Wise RJSet al., 2005,

    Lexical retrieval constrained by sound structure: The role of the left inferior frontal gyrus

    , BRAIN AND LANGUAGE, Vol: 92, Pages: 309-319, ISSN: 0093-934X
  • Journal article
    Sharp DJ, Scott SK, Wise RJS, 2004,

    Retrieving meaning after temporal lobe infarction: The role of the basal language area

    , ANNALS OF NEUROLOGY, Vol: 56, Pages: 836-846, ISSN: 0364-5134
  • Conference paper
    Sharp DJ, Scott SK, Crinion J, Wise RJSet al., 2004,

    Recovery from aphasia: The role of the basal language area

    , Spring Meeting of the Association-of-British-Neurologists, Publisher: B M J PUBLISHING GROUP, Pages: 1217-1218, ISSN: 0022-3050

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