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Book chapterOwen A, Hampshire A, 2009,
The mid-ventrolateral frontal cortex and attentional control
, Neuroimaging in Human Memory: Linking cognitive processes to neural systems., Editors: Rosler, Ranganath, Roder, Kluwe, Oxford, Publisher: OUP Oxford -
Journal articleGoldstone AP, Holland AJ, Hauffa BP, et al., 2008,
Recommendations for the Diagnosis and Management of Prader-Willi Syndrome
, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 93, Pages: 4183-4197, ISSN: 0021-972X- Author Web Link
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- Citations: 333
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Journal articleSharp DJ, 2008,
Cognitive impairment after mild traumatic brain injury - the value of memory testing
, NATURE CLINICAL PRACTICE NEUROLOGY, Vol: 4, Pages: 420-421, ISSN: 1745-834X- Author Web Link
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- Citations: 1
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Conference paperSharp DJ, Turkheimer F, Bose S, et al., 2008,
The control of language after brain injury: Changing fronto-parietal interactions after aphasic stroke
, Annual Meeting of the Association-of-British-Neurologists, Publisher: B M J PUBLISHING GROUP, Pages: 343-343, ISSN: 0022-3050 -
Journal articleWilliams-Gray CH, Hampshire A, Barker RA, et al., 2008,
Attentional control in Parkinson's disease is dependent on COMT val 158 met genotype
, Brain, Vol: 131, Pages: 397-408, ISSN: 1460-2156Cognitive 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.
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Journal articleChamberlain SR, Menzies L, Hampshire A, et al., 2008,
Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives
, Science, Vol: 321, Pages: 421-422, ISSN: 1095-9203Obsessive-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.
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Journal articleHampshire A, Gruszka A, Fallon SJ, et 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: 0898-929XStudies 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.
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Journal articlePassamonti L, Rowe JB, Ewbank M, et 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: 1053-8119For 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.
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Journal articleHampshire A, Thompson R, Duncan J, et al., 2008,
The target selective neural response--similarity, ambiguity, and learning effects
, PLoS One, Vol: 3, ISSN: 1932-6203A 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.
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Journal articleDassan P, Clarke C, Sharp DJ, 2007,
A Case of Poststreptococcal Opsoclonus-Myoclonus Syndrome
, Movement Disorders, Vol: 10, Pages: 1490-1491, ISSN: 1531-8257High 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.
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