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Journal articleChamberlain SR, Hampshire A, Müller U, et al., 2009,
Atomoxetine Modulates Right Inferior Frontal Activation During Inhibitory Control: A Pharmacological Functional Magnetic Resonance Imaging Study
, Biological Psychiatry, Vol: 65, Pages: 550-555, ISSN: 0006-3223BACKGROUND: Atomoxetine, a selective noradrenaline reuptake inhibitor (SNRI) licensed for the treatment of attention-deficit/hyperactivity disorder (ADHD), has been shown to improve response inhibition in animals, healthy volunteers, and adult patients. However, the mechanisms by which atomoxetine improves inhibitory control have yet to be determined. METHODS: The effects of atomoxetine (40 mg) were measured with a stop-signal functional magnetic resonance imaging (fMRI) paradigm in 19 healthy volunteers, in a within-subject, double-blind, placebo-controlled design. RESULTS: Atomoxetine improved inhibitory control and increased activation in the right inferior frontal gyrus when volunteers attempted to inhibit their responses (irrespective of success). Plasma levels of drug correlated significantly with right inferior frontal gyrus activation only during successful inhibition. CONCLUSIONS: These results show that atomoxetine exerts its beneficial effects on inhibitory control via modulation of right inferior frontal function, with implications for understanding and treating inhibitory dysfunction of ADHD and other disorders.
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Journal articleBerry E, Hampshire A, Rowe J, et al., 2009,
The neural basis of effective memory therapy in a patient with limbic encephalitis
, J Neurol Neurosurg Psychiatry, Vol: 80, Pages: 1202-1205, ISSN: 1468-330XBACKGROUND: An fMRI study is described in which a postencephalitic woman with amnesia used a wearable camera which takes photographs passively, without user intervention, to record and review recent autobiographical events. "SenseCam" generates hundreds of images which can subsequently be reviewed quickly or one by one. RESULTS: Memory for a significant event was improved substantially when tested after 4.5 weeks, if the patient viewed SenseCam images of the event every 2 days for 3 weeks. In contrast, after only 3.5 weeks, her memory was at chance levels for a similarly significant event which was reviewed equally often, but using a written diary. During the fMRI scan, the patient viewed images of these two events, plus images of an unrehearsed event and images from a novel "control" event that she had never experienced. There was no difference in behavioural responses or in activation when the unrehearsed and novel conditions were compared. Relative to the written-rehearsed condition, successful recognition of the images in the SenseCam-rehearsed condition was associated with activation of frontal and posterior cortical regions associated with normal episodic memory. CONCLUSION: SenseCam images may provide powerful cues that trigger the recall and consolidation of stored but inaccessible memories.
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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: 352
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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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