Imperial College London

ProfessorAdamHampshire

Faculty of MedicineDepartment of Brain Sciences

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 7993a.hampshire

 
 
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Location

 

Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
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148 results found

Lorenz R, Hampshire A, Leech R, 2016, Neuroadaptive Bayesian Optimization and Hypothesis Testing, TRENDS IN COGNITIVE SCIENCES, Vol: 21, Pages: 155-167, ISSN: 1364-6613

Journal article

Odlaug BL, Hampshire A, Chamberlain SR, Grant JEet al., 2016, Abnormal brain activation in excoriation (skin-picking) disorder: evidence from an executive planning fMRI study., Br J Psychiatry, Vol: 208, Pages: 168-174

BACKGROUND: Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. AIMS: To probe the function of fronto-striatal circuitry in SPD. METHOD: Eighteen participants with SPD and 15 matched healthy controls undertook an executive planning task (Tower of London) during functional magnetic resonance imaging (fMRI). Activation during planning was compared between groups using region of interest and whole-brain permutation cluster approaches. RESULTS: The SPD group exhibited significant functional underactivation in a cluster encompassing bilateral dorsal striatum (maximal in right caudate), bilateral anterior cingulate and right medial frontal regions. These abnormalities were, for the most part, outside the dorsal planning network typically activated by executive planning tasks. CONCLUSIONS: Abnormalities of neural regions involved in habit formation, action monitoring and inhibition appear involved in the pathophysiology of SPD. Implications exist for understanding the basis of excessive grooming and the relationship of SPD with putative obsessive-compulsive spectrum disorders.

Journal article

Lorenz R, Monti RP, Hampshire A, Koush Y, Anagnostopoulos C, Faisal AA, Sharp D, Montana G, Leech R, Violante IRet al., 2016, Towards tailoring non-invasive brain stimulation using real-time fMRI and Bayesian optimization, 6th International Workshop on Pattern Recognition in Neuroimaging (PRNI), Publisher: IEEE, Pages: 49-52, ISSN: 2330-9989

Conference paper

Hampshire A, Hellyer PJ, Parkin B, Hiebert N, MacDonald P, Owen A, Leech R, Rowe JBet al., 2015, Network mechanisms of intentional learning, Neuroimage, Vol: 127, Pages: 123-134, ISSN: 1095-9572

The ability to learn new tasks rapidly is a prominent characteristic of human behaviour. Thisability relies on flexible cognitive systems that adapt in order to encode temporary programs forprocessing non-automated tasks. Previous functional imaging studies have revealed distinctroles for the lateral frontal cortices (LFCs) and the ventral striatum in intentional learningprocesses. However, the human LFCs are complex; they house multiple distinct sub-regions,each of which co-activates with a different functional network. It remains unclear how these LFCnetworks differ in their functions and how they coordinate with each other, and the ventralstriatum, to support intentional learning. Here, we apply a suite of fMRI connectivity methods todetermine how LFC networks activate and interact at different stages of two novel tasks, inwhich arbitrary stimulus-response rules are learnt either from explicit instruction or by trialand-error.We report that the networks activate en masse and in synchrony when novel rules arebeing learnt from instruction. However, these networks are not homogeneous in their functions;instead, the directed connectivities between them vary asymmetrically across the learningtimecourse and they disengage from the task sequentially along a rostro-caudal axis.Furthermore, when negative feedback indicates the need to switch to alternative stimulusresponserules, there is additional input to the LFC networks from the ventral striatum. Theseresults support the hypotheses that LFC networks interact as a hierarchical system duringintentional learning and that signals from the ventral striatum have a driving influence on thissystem when the internal program for processing the task is updated.

Journal article

Hampshire A, Sharp D, 2015, Inferior PFC Subregions Have Broad Cognitive Roles, TRENDS IN COGNITIVE SCIENCES, Vol: 19, Pages: 712-713, ISSN: 1364-6613

Journal article

Corbett A, Owen A, Hampshire A, Grahn J, Stenton R, Dajani S, Burns A, Howard R, Williams N, Williams G, Ballard Cet al., 2015, The Effect of an Online Cognitive Training Package in Healthy Older Adults: An Online Randomized Controlled Trial, Journal of the American Medical Directors Association, Vol: 16, Pages: 990-997, ISSN: 1525-8610

Journal article

Jenkins P, Fleminger J, De-Simoni S, Jolly A, Gorgoraptis N, Hampshire A, Sharp Det al., 2015, HOME COMPUTERISED COGNITIVE TESTING FOR TBI IS FEASIBLE AND POPULAR, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

Conference paper

Hampshire A, Sharp DJ, 2015, Contrasting network and modular perspectives on inhibitory control., Trends in Cognitive Sciences, ISSN: 1364-6613

A prominent theory proposes that the right inferior frontal cortex of the human brain houses a dedicated region for motor response inhibition. However, there is growing evidence to support the view that this inhibitory control hypothesis is incorrect. Here, we discuss evidence in favour of our alternative hypothesis, which states that response inhibition is one example of a broader class of control processes that are supported by the same set of frontoparietal networks. These domain-general networks exert control by modulating local lateral inhibition processes, which occur ubiquitously throughout the cortex. We propose that to fully understand the neural basis of behavioural control requires a more holistic approach that considers how common network mechanisms support diverse cognitive processes.

Journal article

Parkin BL, Hellyer PJ, Leech R, Hampshire Aet al., 2015, Dynamic network mechanisms of relational integration, Journal of Neuroscience, Vol: 35, Pages: 7660-7673, ISSN: 1529-2401

© 2015 Parkin et al. A prominent hypothesis states that specialized neural modules within the human lateral frontopolar cortices (LFPCs) support “relational integration” (RI), the solving of complex problems using inter-related rules. However, it has been proposed that LFPC activity during RI could reflect the recruitment of additional “domain-general” resources when processing more difficult problems in general as opposed to RI specifically. Moreover, theoretical research with computational models has demonstrated that RI may be supported by dynamic processes that occur throughout distributed networks of brain regions as opposed to within a discrete computational module. Here, we present fMRI findings from a novel deductive reasoning paradigm that controls for general difficulty while manipulating RI demands. In accordance with the domaingeneral perspective, we observe an increase in frontoparietal activation during challenging problems in general as opposed to RI specifically. Nonetheless, when examining frontoparietal activity using analyses of phase synchrony and psychophysiological interactions, we observe increased network connectivity during RI alone. Moreover, dynamic causal modeling with Bayesian model selection identifies the LFPC as the effective connectivity source. Based on these results, we propose that during RI an increase in network connectivity and a decrease in network metastability allows rules that are coded throughout working memory systems to be dynamically bound. This change in connectivity state is top-down propagated via a hierarchical system of domain-general networks with the LFPC at the apex. In this manner, the functional network perspective reconciles key propositions of the globalist, modular, and computational accounts of RI within a single unified framework.

Journal article

Kirschner A, Cruse D, Chennu S, Owen A, Hampshire Aet al., 2015, A P300-based cognitive assessment battery, Brain and Behavior, Vol: 5, ISSN: 2162-3279

Background: It is well established that some patients who are diagnosed as being in a vegetative state or a minimally conscious state show reliable signs of volition that may only be detected by measuring neural responses. A pertinent question is whether these patients are capable of higher cognitive processes. Methods: Here, we develop a series of EEG paradigms that probe several core aspects of cognition at the bedside without the need for motor responses and explore the sensitivity of this approach in a group of healthy controls. Results: Using analysis of ERPs alone, this method can determine with high reliability whether individual participants are able to attend a stimulus stream, maintain items in working memory, or solve complex grammatical reasoning problems. Conclusion: We suggest that this approach could form the basis of a brain-based battery for assessing higher cognition in patients with severe motor impairments or disorders of consciousness.

Journal article

Mason SL, Zhang J, Begeti F, Guzman NV, Lazar AS, Rowe JB, Barker RA, Hampshire Aet al., 2015, The role of the amygdala during emotional processing in Huntington's disease: from pre-manifest to late stage disease., Neuropsychologia, Vol: 70, Pages: 80-89

BACKGROUND: Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis. METHODS: We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: "the Reading the Mind in the Eyes Test" which has been previously been shown to be amygdala dependent. RESULTS: Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, p<0.05). Furthermore, performance on the "Reading the Mind in the Eyes Test" correlated negatively with proximity to disease onset and became progressively worse with each stage of disease. CONCLUSION: Abnormalities in the neural networks underlying social cognition and emotional processing can be detected pr

Journal article

Hampshire A, 2015, Putting the brakes on inhibitory models of frontal lobe function, Neuroimage, Vol: 113, Pages: 340-355, ISSN: 1095-9572

There has been much recent debate regarding the neural basis of motor response inhibition. An influential hypothesis from the last decade proposes that a module within the right inferior frontal cortex (RIFC) of the human brain is dedicated to supporting response inhibition. However, there is growing evidence to support the alternative view that response inhibition is just one prominent example of the many cognitive control processes that are supported by the same set of 'domain general' functional networks. Here, I test directly between the modular and network accounts of motor response inhibition by applying a combination of data-driven, event-related and functional connectivity analyses to fMRI data from a variety of attention and inhibition tasks. The results demonstrate that there is no inhibitory module within the RIFC. Instead, response inhibition recruits a functionally heterogeneous ensemble of RIFC networks, which can be dissociated from each other in the context of other task demands.

Journal article

Winder-Rhodes SE, Hampshire A, Rowe JB, Peelle JE, Robbins TW, Owen AM, Barker RAet al., 2015, Association between MAPT haplotype and memory function in patients with Parkinson's disease and healthy aging individuals, Neurobiology of Aging, Vol: 36, Pages: 1519-1528, ISSN: 0197-4580

Genetic variation is associated with differences in the function of the brain as well as its susceptibility to disease. The common H1 haplotypic variant of the microtubule-associated protein tau gene (MAPT) has been related to an increased risk for Parkinson's disease (PD). Furthermore, among PD patients, H1 homozygotes have an accelerated progression to dementia. We investigated the neurocognitive correlates of MAPT haplotypes using functional magnetic resonance imaging. Thirty-seven nondemented patients with PD (19 H1/H1, 18 H2 carriers) and 40 age-matched controls (21 H1/H1, 19 H2 carriers) were scanned during performance of a picture memory encoding task. Behaviorally, H1 homozygosity was associated with impaired picture recognition memory in PD patients and control subjects. These impairments in the H1 homozygotes were accompanied by an altered blood-oxygen level-dependent response in the medial temporal lobe during successful memory encoding. Additional age-related differences in blood-oxygen level-dependent response were observed in the medial temporal lobes of H1 homozygotes with PD. These results suggest that common variation in MAPT is not only associated with the dementia of PD but also differences in the neural circuitry underlying aspects of cognition in normal aging.

Journal article

Winder-Rhodes SE, Hampshire A, Rowe JB, Peelle JE, Robbins TW, Owen AM, Barker RAet al., 2015, Association between MAPT haplotype and memory function in patients with Parkinson's disease and healthy aging individuals., Neurobiol Aging, Vol: 36, Pages: 1519-1528

Genetic variation is associated with differences in the function of the brain as well as its susceptibility to disease. The common H1 haplotypic variant of the microtubule-associated protein tau gene (MAPT) has been related to an increased risk for Parkinson's disease (PD). Furthermore, among PD patients, H1 homozygotes have an accelerated progression to dementia. We investigated the neurocognitive correlates of MAPT haplotypes using functional magnetic resonance imaging. Thirty-seven nondemented patients with PD (19 H1/H1, 18 H2 carriers) and 40 age-matched controls (21 H1/H1, 19 H2 carriers) were scanned during performance of a picture memory encoding task. Behaviorally, H1 homozygosity was associated with impaired picture recognition memory in PD patients and control subjects. These impairments in the H1 homozygotes were accompanied by an altered blood-oxygen level-dependent response in the medial temporal lobe during successful memory encoding. Additional age-related differences in blood-oxygen level-dependent response were observed in the medial temporal lobes of H1 homozygotes with PD. These results suggest that common variation in MAPT is not only associated with the dementia of PD but also differences in the neural circuitry underlying aspects of cognition in normal aging.

Journal article

Scott G, Hellyer PJ, Hampshire A, Leech Ret al., 2014, Exploring spatiotemporal network transitions in task functional MRI, Hum. Brain Mapp., Pages: n/a-n/a, ISSN: 1097-0193

Journal article

Hiebert NM, Vo A, Hampshire A, Owen AM, Seergobin KN, MacDonald PAet al., 2014, Striatum in stimulus-response learning via feedback and in decision making., Neuroimage, Vol: 101, Pages: 448-457

Cognitive deficits are recognized in Parkinson's disease. Understanding cognitive functions mediated by the striatum can clarify some of these impairments and inform treatment strategies. The dorsal striatum, a region impaired in Parkinson's disease, has been implicated in stimulus-response learning. However, most investigations combine acquisition of associations between stimuli, responses, or outcomes (i.e., learning) and expression of learning through response selection and decision enactment, confounding these separate processes. Using neuroimaging, we provide evidence that dorsal striatum does not mediate stimulus-response learning from feedback but rather underlies decision making once associations between stimuli and responses are learned. In the experiment, 11 males and 5 females (mean age 22) learned to associate abstract images to specific button-press responses through feedback in Session 1. In Session 2, they were asked to provide responses learned in Session 1. Feedback was omitted, precluding further feedback-based learning in this session. Using functional magnetic resonance imaging, dorsal striatum activation in healthy young participants was observed at the time of response selection and not during feedback, when greatest learning presumably occurs. Moreover, dorsal striatum activity increased across the duration of Session 1, peaking after most associations were well learned, and was significant during Session 2 where no feedback was provided, and therefore no feedback-based learning occurred. Preferential ventral striatum activity occurred during feedback and was maximal early in Session 1. Taken together, the results suggest that the ventral striatum underlies learning associations between stimuli and responses via feedback whereas the dorsal striatum mediates enacting decisions.

Journal article

Nombela C, Rowe JB, Winder-Rhodes SE, Hampshire A, Owen AM, Breen DP, Duncan GW, Khoo TK, Yarnall AJ, Firbank MJ, Chinnery PF, Robbins TW, O'Brien JT, Brooks DJ, Burn DJ, Barker RAet al., 2014, Genetic impact on cognition and brain function in newly diagnosed Parkinson's disease: ICICLE-PD study, Brain, Vol: 137, Pages: 2743-2758, ISSN: 0006-8950

Parkinson’s disease is associated with multiple cognitive impairments and increased risk of dementia, but the extent of these deficits varies widely among patients. The ICICLE-PD study was established to define the characteristics and prevalence of cognitive change soon after diagnosis, in a representative cohort of patients, using a multimodal approach. Specifically, we tested the ‘Dual Syndrome’ hypothesis for cognitive impairment in Parkinson’s disease, which distinguishes an executive syndrome (affecting the frontostriatal regions due to dopaminergic deficits) from a posterior cortical syndrome (affecting visuospatial, mnemonic and semantic functions related to Lewy body pathology and secondary cholinergic loss). An incident Parkinson’s disease cohort (n = 168, median 8 months from diagnosis to participation) and matched control group (n = 85) were recruited to a neuroimaging study at two sites in the UK. All participants underwent clinical, neuropsychological and functional magnetic resonance imaging assessments. The three neuroimaging tasks (Tower of London, Spatial Rotations and Memory Encoding Tasks) were designed to probe executive, visuospatial and memory encoding domains, respectively. Patients were also genotyped for three polymorphisms associated with cognitive change in Parkinson’s disease and related disorders: (i) rs4680 for COMT Val158Met polymorphism; (ii) rs9468 for MAPT H1 versus H2 haplotype; and (iii) rs429358 for APOE-ε2, 3, 4. We identified performance deficits in all three cognitive domains, which were associated with regionally specific changes in cortical activation. Task-specific regional activations in Parkinson’s disease were linked with genetic variation: the rs4680 polymorphism modulated the effect of levodopa therapy on planning-related activations in the frontoparietal network; the MAPT haplotype modulated parietal activations associated with spatial rotations; and APOE allelic varia

Journal article

Mason S, Zhang J, Rowe J, Barker R, Hampshire Aet al., 2014, FRONTOSTRIATAL ABNORMALITIES IN HUNTINGTON'S DISEASE: AN FMRI STUDY, 8th European-Huntington's-Disease-Network Plenary Meeting, Publisher: BMJ PUBLISHING GROUP, Pages: A45-A45, ISSN: 0022-3050

Conference paper

Erika-Florence M, Leech R, Hampshire A, 2014, A functional network perspective on response inhibition and attentional control, NATURE COMMUNICATIONS, Vol: 5, ISSN: 2041-1723

Journal article

Herrera PM, Speranza M, Hampshire A, Bekinschtein TAet al., 2014, Monetary rewards modulate inhibitory control, Frontiers in Human Neuroscience, Vol: 8

The ability to override a dominant response, often referred to as behavioral inhibition, is considered a key element of executive cognition. Poor behavioral inhibition is a defining characteristic of several neurological and psychiatric populations. Recently, there has been increasing interest in the motivational dimension of behavioral inhibition, with some experiments incorporating emotional contingencies in classical inhibitory paradigms such as the Go/NoGo and Stop Signal Tasks (SSTs). Several studies have reported a positive modulatory effect of reward on performance in pathological conditions such as substance abuse, pathological gambling, and Attention Deficit Hyperactive Disorder (ADHD). However, experiments that directly investigate the modulatory effects of reward magnitudes on the performance of inhibitory tasks are scarce and little is known about the finer grained relationship between motivation and inhibitory control. Here we probed the effect of reward magnitude and context on behavioral inhibition with three modified versions of the widely used SST. The pilot study compared inhibition performance during six blocks alternating neutral feedback, low, medium, and high monetary rewards. Study One compared increasing vs. decreasing rewards, with low, high rewards, and neutral feedback; whilst Study Two compared low and high reward magnitudes alone also in an increasing and decreasing reward design. The reward magnitude effect was not demonstrated in the pilot study, probably due to a learning effect induced by practice in this lengthy task. The reward effect per se was weak but the context (order of reward) was clearly suggested in Study One, and was particularly strongly confirmed in study two. In addition, these findings revealed a "kick start effect" over global performance measures. Specifically, there was a long lasting improvement in performance throughout the task when participants received the highest reward magnitudes at the beginning o

Journal article

Hoppitt L, Illingworth JL, MacLeod C, Hampshire A, Dunn BD, Mackintosh Bet al., 2014, Modifying social anxiety related to a real-life stressor using online Cognitive Bias Modification for interpretation, Behaviour Research and Therapy, Vol: 52, Pages: 45-52, ISSN: 0005-7967

Journal article

Hampshire A, MacDonald A, Owen AM, 2013, Hypoconnectivity and Hyperfrontality in Retired American Football Players, Scientific Reports, Vol: 3

Journal article

Schweizer S, Grahn J, Hampshire A, Mobbs D, Dalgleish Tet al., 2013, Training the emotional brain: improving affective control through emotional working memory training., J Neurosci, Vol: 33, Pages: 5301-5311

Affective cognitive control capacity (e.g., the ability to regulate emotions or manipulate emotional material in the service of task goals) is associated with professional and interpersonal success. Impoverished affective control, by contrast, characterizes many neuropsychiatric disorders. Insights from neuroscience indicate that affective cognitive control relies on the same frontoparietal neural circuitry as working memory (WM) tasks, which suggests that systematic WM training, performed in an emotional context, has the potential to augment affective control. Here we show, using behavioral and fMRI measures, that 20 d of training on a novel emotional WM protocol successfully enhanced the efficiency of this frontoparietal demand network. Critically, compared with placebo training, emotional WM training also accrued transfer benefits to a "gold standard" measure of affective cognitive control-emotion regulation. These emotion regulation gains were associated with greater activity in the targeted frontoparietal demand network along with other brain regions implicated in affective control, notably the subgenual anterior cingulate cortex. The results have important implications for the utility of WM training in clinical, prevention, and occupational settings.

Journal article

Hampshire A, Parkin BL, Cusack R, Fernández Espejoa D, Allanson J, Kamau E, Pickard JD, Owen AMet al., 2013, Assessing residual reasoning ability in overtly non-communicative patients using fMRI, NeuroImage: Clinical, Vol: 2, Pages: 174-183

Journal article

Fallon SJ, Hampshire A, Williams-Gray CH, Barker RA, Owen AMet al., 2013, Putative cortical dopamine levels affect cortical recruitment during planning, Neuropsychologia, ISSN: 1873-3514

Planning, the decomposition of an ultimate goal into a number of sub-goals is critically dependent upon fronto-striatal dopamine (DA) levels. Here, we examined the extent to which the val158met polymorphism in the catechol O-methyltransferase (COMT) gene, which is thought to primarily alter cortical DA levels, affects performance and fronto-parietal activity during a planning task (Tower of London). COMT genotype was found to modulate activity in the left superior posterior parietal cortex (SPC) during planning, relative to subtracting, trials. Specifically, left SPC blood oxygenation level-dependent (BOLD) response was reduced in groups with putatively low or high cortical DA levels (COMT homozygotes) relative to those with intermediate cortical DA levels (COMT heterozygotes). These set of results are argued to occur either due to differences in neuronal processing in planning (and perhaps subtracting) caused by the COMT genotype and/or the cognitively heterogeneous nature of the TOL, which allows different cognitive strategies to be used whilst producing indistinguishable behavioural performance in healthy adults. The implications of this result for our understanding of COMT's effect on cognition in health and disease are discussed.

Journal article

Cinan S, Özen G, Hampshire A, 2013, Confirmatory factor analysis on separability of planning and insight constructs, Journal of Cognitive Psychology

Journal article

Grant JE, Odlaug BL, Hampshire A, Schreiber LR, Chamberlain SRet al., 2013, White matter abnormalities in skin picking disorder: a diffusion tensor imaging study, Neuropsychopharmacology, Vol: 38, Pages: 763-769, ISSN: 1740-634X

Skin picking disorder (SPD) is characterized by the repetitive and compulsive picking of skin, resulting in tissue damage. Neurocognitive findings in SPD implicate difficulty with response inhibition (suppression of pre-potent motor responses). This function is dependent on the integrity of the right frontal gyrus and the anterior cingulate cortices, and white-matter tracts connecting such neural nodes. It was hypothesized that SPD would be associated with reduced fractional anisotropy in regions implicated in top-down response suppression, particularly white-matter tracts in proximity of the bilateral anterior cingulate and right frontal (especially orbitofrontal and inferior frontal) cortices. 13-subjects meeting proposed SPD criteria for DSM-5 free from other current psychiatric comorbidities, and 12 healthy comparison subjects underwent MRI with a 3-T system. Between-group comparisons of imaging data underwent voxelwise analysis with permutation modeling and cluster correction. Fractional anisotropy (measured using diffusion tensor imaging) was the primary outcome measure. Subjects with SPD exhibited significantly reduced fractional anisotropy in tracts distributed bilaterally, which included the anterior cingulate cortices. Fractional anisotropy did not correlate significantly with SPD disease severity, or depressive or anxiety scores. These findings implicate disorganization of white-matter tracts involved in motor generation and suppression in the pathophysiology of SPD, findings remarkably similar to those previously reported in trichotillomania. This study adds considerable support to the notion that-in addition to the phenomenological and comorbid overlap between SPD and trichotillomania-these disorders likely share overlapping neurobiology.

Journal article

Fallon SJ, Williams-Gray CH, Barker RA, Owen AM, Hampshire Aet al., 2013, Prefrontal dopamine levels determine the balance between cognitive stability and flexibility, Cereb Cortex, Vol: 23, Pages: 361-369, ISSN: 1460-2199

A key mechanism by which the prefrontal cortex (PFC) supports goal-oriented behaviors is attentional set formation: the formation and maintenance of an attentional bias toward relevant features. It has previously been proposed that a common single nucleotide polymorphism (val158met) in the gene that codes for the catechol O-methyltransferase (COMT) enzyme may affect an individual's ability to form and maintain an attentional set by modulating PFC dopamine (DA) levels. Here, we present data from a functional magnetic resonance imaging study that investigated the effect of this polymorphism on the tendency for older adults to display set-like behavior, and we compare these results to preexisting data from Parkinson's Disease (PD) patients. Our results demonstrate that putatively different levels of PFC DA predict both attentional set formation and right dorsolateral PFC (DLPFC) activation. More specifically, while for PD patients, val homozygotes showed heightened DLPFC activation and increased set-like behavior, for healthy older adults, the opposite pattern of results was observed. This interaction between COMT genotype and PD accords well with previous studies that have shown an excess of DA in the PFC in early PD patients and, furthermore, supports the hypothesis that there is an inverted-U shaped functional relationship between PFC DA levels and attentional set formation.

Journal article

Grant JE, Odlaug BL, Chamberlain SR, Hampshire A, Schreiber L, Won Kim Set al., 2013, A Proof of Concept Study of Tolcapone for Pathological Gambling: Relationships with COMT Genotype and Brain Activation, European Neuropsychopharmacology

Journal article

Owen AM, Hampshire A, 2012, The mid-ventrolateral frontal cortex and attentional control, Neuroimaging of Human Memory: Linking Cognitive Processes to Neural Systems, ISBN: 9780199217298

This chapter examines neuroimaging evidence that suggests that the mid-ventrolateral frontal cortex plays a specific role in intended action; that is, any behaviour that is consciously willed by the agent responsible for carrying out that behaviour. In this sense, it makes contributions to both memory and attention in a manner that cannot be predicted by current psychological models of either cognitive system.

Book chapter

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