Imperial College London

DrAdamHampshire

Faculty of MedicineDepartment of Medicine

Senior Lecturer in Restorative Neurosciences
 
 
 
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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
to

86 results found

Hampshire A, Daws RE, Neves ID, Soreq E, Sandrone S, Violante IRet al., 2019, Probing cortical and sub-cortical contributions to instruction-based learning: Regional specialisation and global network dynamics, NeuroImage, Vol: 192, Pages: 88-100, ISSN: 1053-8119

Diverse cortical networks and striatal brain regions are implicated in instruction-based learning (IBL); however, their distinct contributions remain unclear. We use a modified fMRI paradigm to test two hypotheses regarding the brain mechanisms that underlie IBL. One hypothesis proposes that anterior caudate and frontoparietal regions transiently co-activate when new rules are being bound in working memory. The other proposes that they mediate the application of the rules at different stages of the consolidation process. In accordance with the former hypothesis, we report strong activation peaks within and increased connectivity between anterior caudate and frontoparietal regions when rule-instruction slides are presented. However, similar effects occur throughout a broader set of cortical and sub-cortical regions, indicating a metabolically costly reconfiguration of the global brain state. The distinct functional roles of cingulo-opercular, frontoparietal and default-mode networks are apparent from their activation throughout, early and late in the practice phase respectively. Furthermore, there is tentative evidence of a peak in anterior caudate activity mid-way through the practice stage. These results demonstrate how performance of the same simple task involves a steadily shifting balance of brain systems as learning progresses. They also highlight the importance of distinguishing between regional specialisation and global dynamics when studying the network mechanisms that underlie cognition and learning.

JOURNAL ARTICLE

Soreq E, Hampshire A, Leech R, 2019, Dynamic network coding of working-memory domains and working-memory processes, Nature Communications, ISSN: 2041-1723

The classic mapping of distinct aspects of working memory (WM) to mutually exclusive brain areas is at odds with the distributed processing mechanisms proposed by contemporary network science theory. Here, we use machinelearning to determine how aspects of WM are dynamically coded in the human brain. Using cross-validation across independent fMRI studies, we demonstrate that stimulus domains (spatial, number and fractal) and WM processes(encode, maintain, probe) are classifiable with high accuracy from the patterns of network activity and connectivitythat they evoke. This is the case even when focusing on ‘multiple demands’ brain regions, which are active across all WM conditions. Contrary to early neuropsychological perspectives, these aspects of WM do not map exclusively tobrain areas or processing streams; however, the mappings from that literature form salient features within the corresponding multivariate connectivity patterns. Furthermore, connectivity patterns provide the most precise basis for classification and become fine-tuned as maintenance load increases. These results accord with a network-codingmechanism, where the same brain regions support diverse WM demands by adopting different connectivity states.

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Li L, Ribeiro Violante I, Leech R, Ross E, Hampshire A, Opitz A, Rothwell J, Carmichael D, Sharp Det al., 2019, Brain state and polarity dependent modulation of brain networks by transcranial direct current stimulation, Human Brain Mapping, Vol: 40, Pages: 904-915, ISSN: 1065-9471

Despite its widespread use in cognitive studies, there is still limited understanding of whether and how transcranial direct current stimulation (tDCS) modulates brain network function. To clarify its physiological effects, we assessed brain network function using functional magnetic resonance imaging (fMRI) simultaneously acquired during tDCS stimulation. Cognitive state was manipulated by having subjects perform a Choice Reaction Task or being at “rest.” A novel factorial design was used to assess the effects of brain state and polarity. Anodal and cathodal tDCS were applied to the right inferior frontal gyrus (rIFG), a region involved in controlling activity large‐scale intrinsic connectivity networks during switches of cognitive state. tDCS produced widespread modulation of brain activity in a polarity and brain state dependent manner. In the absence of task, the main effect of tDCS was to accentuate default mode network (DMN) activation and salience network (SN) deactivation. In contrast, during task performance, tDCS increased SN activation. In the absence of task, the main effect of anodal tDCS was more pronounced, whereas cathodal tDCS had a greater effect during task performance. Cathodal tDCS also accentuated the within‐DMN connectivity associated with task performance. There were minimal main effects of stimulation on network connectivity. These results demonstrate that rIFG tDCS can modulate the activity and functional connectivity of large‐scale brain networks involved in cognitive function, in a brain state and polarity dependent manner. This study provides an important insight into mechanisms by which tDCS may modulate cognitive function, and also has implications for the design of future stimulation studies.

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Creese B, Brooker H, Ismail Z, Wesnes KA, Hampshire A, Khan Z, Megalogeni M, Corbett A, Aarsland D, Ballard Cet al., 2019, Mild Behavioral Impairment as a Marker of Cognitive Decline in Cognitively Normal Older Adults, American Journal of Geriatric Psychiatry, ISSN: 1064-7481

© 2019 American Association for Geriatric Psychiatry Objective: Mild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by later life emergent neuropsychiatric symptoms (NPS) that represent an at-risk state for incident cognitive decline and dementia in people with mild cognitive impairment (MCI). We undertook a study to determine whether MBI was associated with progressive changes in neuropsychological performance in people without significant cognitive impairment. Methods: A total of 9,931 older adults enrolled in the PROTECT study who did not have MCI or dementia undertook a comprehensive neuropsychological battery measuring attention, reasoning, executive function, and working memory at baseline and 1 year. MBI was ascertained using self-administration of the Mild Behavioral Impairment Checklist at 1 year, and participants were grouped according to MBI status: No Symptoms, Intermediate NPS and MBI. All assessments were completed online, and data analyzed using mixed-effects model repeated measures analysis of covariance. Results: A total of 949 (10%) people had MBI. These individuals had significantly worse cognitive performance at baseline and significantly greater decline over 1 year in the four composite cognitive scores measuring attentional intensity (F [2,8578] = 3.97; p = 0.019), sustained attention (F [2,8578] = 18.63; p <0.0001), attentional fluctuation (F [2,8578] = 10.13; p <0.0001) and working memory (F [2,9895] = 13.1; p <0.0001). Conclusion: Our novel findings show that MBI is associated with faster decline in attention and working memory in this cognitively normal sample. MBI may be an earlier marker of neurodegenerative disease than MCI, captured at the stage of subjective cognitive decline or before, raising the possibility that MBI represents a novel target for dementia clinical trials or prevention strategies.

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Li L, Ribeiro Violante I, Leech R, Hampshire A, Opitz A, McArhur D, Carmichael D, Sharp Det al., 2019, Cognitive enhancement with Salience Network electrical stimulation is influenced by network structural connectivity, NeuroImage, Vol: 185, Pages: 425-433, ISSN: 1053-8119

The Salience Network (SN) and its interactions are important for cognitive control. We have previously shown that structural damage to the SN is associated with abnormal functional connectivity between the SN and Default Mode Network (DMN), abnormal DMN deactivation, and impaired response inhibition, which is an important aspect of cognitive control. This suggests that stimulating the SN might enhance cognitive control. Here, we tested whether non-invasive transcranial direct current stimulation (TDCS) could be used to modulate activity within the SN and enhance cognitive control. TDCS was applied to the right inferior frontal gyrus/anterior insula cortex during performance of the Stop Signal Task (SST) and concurrent functional (f)MRI. Anodal TDCS improved response inhibition. Furthermore, stratification of participants based on SN structural connectivity showed that it was an important influence on both behavioural and physiological responses to anodal TDCS. Participants with high fractional anisotropy within the SN showed improved SST performance and increased activation of the SN with anodal TDCS, whilst those with low fractional anisotropy within the SN did not. Cathodal stimulation of the SN produced activation of the right caudate, an effect which was not modulated by SN structural connectivity. Our results show that stimulation targeted to the SN can improve response inhibition, supporting the causal influence of this network on cognitive control and confirming it as a target to produce cognitive enhancement. Our results also highlight the importance of structural connectivity as a modulator of network to TDCS, which should guide the design and interpretation of future stimulation studies.

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Brooker H, Wesnes KA, Ballard C, Hampshire A, Aarsland D, Khan Z, Stenton R, Megalogeni M, Corbett Aet al., 2019, The relationship between the frequency of number-puzzle use and baseline cognitive function in a large online sample of adults aged 50 and over, International Journal of Geriatric Psychiatry, ISSN: 0885-6230

© 2019 John Wiley & Sons, Ltd. Objective: Establishing affordable lifestyle interventions that might preserve cognitive function in the aging population and subsequent generations is a growing area of research focus. Data from the PROTECT study has been utilised to examine whether number-puzzle use is related to cognitive function in older adults. Methods: Data from 19 078 healthy volunteers aged 50 to 93 years old enrolled on the online PROTECT study were evaluated for self-reported frequency of performing number puzzles. Two cognitive-test batteries were employed to assess core aspects of cognitive function including reasoning, focussed and sustained attention, information processing, executive function, working memory, and episodic memory. Analysis of covariance was used to establish the differences between the six frequency groups. Results: Highly statistically significant main effects of the frequency of performing number puzzles were seen on all 14 cognitive measures, with P values of less than 0.0004. Interestingly, participants who reported engaging in number puzzles more than once a day had superior cognitive performance on 10 core measures compared with all other frequency groups, although not all were statistically significant. Conclusions: This study has identified a close relationship between frequency of number-puzzle use and the quality of cognitive function in adults aged 50 to 93 years old. In order to determine the value of these findings as a potential intervention, further research should explore the type and difficulty of the number puzzles. These findings further contribute to the growing evidence that engaging in mentally stimulating activities could benefit the brain function of the ageing population.

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Peers PV, Astle DE, Duncan J, Murphy FC, Hampshire A, Das T, Manly Tet al., 2018, Dissociable effects of attention vs working memory training on cognitive performance and everyday functioning following fronto-parietal strokes, Neuropsychological Rehabilitation, ISSN: 0960-2011

© 2018, © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. Difficulties with attention are common following stroke, particularly in patients with frontal and parietal damage, and are associated with poor outcome. Home-based online cognitive training may have the potential to provide an efficient and effective way to improve attentional functions in such patients. Little work has been carried out to assess the efficacy of this approach in stroke patients, and the lack of studies with active control conditions and rigorous evaluations of cognitive functioning pre and post-training means understanding is limited as to whether and how such interventions may be effective. Here, in a feasibility pilot study, we compare the effects of 20 days of cognitive training using either novel Selective Attention Training (SAT) or commercial Working Memory Training (WMT) programme, versus a waitlist control on a range of attentional and working memory tasks. We demonstrate separable effects of each training condition, with SAT leading to improvements in spatial and non-spatial aspects of attention and WMT leading to improvements on closely related working memory tasks. In addition, both training groups reported improvements in everyday functioning, which were associated with improvements in attention, suggesting that improving attention may be of particular importance in maximising functional improvements in this patient group.

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Haijen ECHM, Kaelen M, Roseman L, Timmermann C, Russ S, Nutt D, Daws R, Hampshire A, Lorenz R, Carhart-Harris Ret al., 2018, Predicting responses to psychedelics: a prospective study, Frontiers in Pharmacology, Vol: 9, ISSN: 1663-9812

Responses to psychedelics are notoriously difficult to predict, yet significant work is currently underway to assess their therapeutic potential and the level of interest in psychedelics among the general public appears to be increasing. We aimed to collect prospective data in order to improve our ability to predict acute- and longer-term responses to psychedelics. Individuals who planned to take a psychedelic through their own initiative participated in an online survey (www.psychedelicsurvey.com). Traits and variables relating to set, setting and the acute psychedelic experience were measured at five different time points before and after the experience. Principle component and regression methods were used to analyse the data. Sample sizes for the five time points included N= 654, N= 535, N= 379, N= 315, and N= 212 respectively. Psychological well-being was increased two weeks after a psychedelic experience and remained at this level after four weeks. This increase was larger for individuals who scored higher for a ‘mystical-type experience’, and smaller for those who scored higher for ‘challenging experience’. Having ‘clear intentions’ for the experience was conducive to mystical-type experiences. Having a positive ‘set’, as well as having the experience with intentions related to ‘recreation’, were both found to decrease the likelihood of having a challenging experience. The trait ‘absorption’ and higher drug doses promoted both mystical-type and challenging experiences. When comparing different types of variables, traits variables seemed to explain most variance in the change in well-being after a psychedelic experience. These results confirm the importance of extra-pharmacological factors in determining responses to a psychedelic. We view this study as an early step towards the development of empirical guidelines that can evolve and improve iteratively with the ultimate purpose of guiding

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Li W, Lao-Kaim N, Roussakis A, Martin-Bastida A, Valle-Guzman N, Paul G, Soreq E, Daws R, Foltynie T, Barker R, Hampshire A, Piccini Pet al., 2018, Functional connectivity changes in relation to dopaminergic decline in Parkinson's over time: A resting-state fMRI and 11C-PE2I PET imaging study, International Congress of Parkinson's Disease and Movement Disorders, Publisher: WILEY, Pages: S682-S683, ISSN: 0885-3185

CONFERENCE PAPER

Grant JE, Daws R, Hampshire A, Chamberlain SRet al., 2018, An fMRI Pilot Study of Cognitive Flexibility in Trichotillomania., J Neuropsychiatry Clin Neurosci, Vol: 30, Pages: 318-324

Trichotillomania is a relatively common psychiatric condition, although its neurobiological basis is unknown. Abnormalities of flexible responding have been implicated in the pathophysiology of obsessive-compulsive disorder and thus may be relevant in trichotillomania. The purpose of this study was to probe reversal learning and attentional set-shifting in trichotillomania. Twelve adults with trichotillomania and 13 matched healthy control subjects undertook a functional MRI task of cognitive flexibility. Group-level activation maps for extradimensional and reversal switches were independently parcellated into discrete regions of interest using a custom watershed algorithm. Activation magnitudes were extracted from each region of interest and study subject and compared at the group level. Reversal events evoked the expected patterns of insula and parietal regions and activity in the frontal dorsal cortex extending anterior to the frontal poles, whereas extradimensional shifts evoked the expected frontal dorsolateral and parietal pattern of activity. Trichotillomania was associated with significantly increased right middle frontal and reduced right occipital cortex activation during reversal and set-shifting. Elevated frontal activation coupled with reduced activation in more posterior brain regions was identified. These pilot data suggest potentially important neural dysfunction associated with trichotillomania.

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Li W, Lao-Kaim NP, Roussakis A, Martin-Bastida A, Valle-Guzman N, Paul G, Soreq E, Daws RE, Foltynie T, Barker R, Hampshire A, Piccini Pet al., 2018, Functional connectivity changes in relation to dopaminergic decline in Parkinson's over time: a resting-state fMRI and 11C-PE2I PET imaging study, 4th Congress of the European-Academy-of-Neurology (EAN), Publisher: WILEY, Pages: 345-345, ISSN: 1351-5101

CONFERENCE PAPER

Lorenz R, Ribeiro Violante I, Monti R, Montana G, Hampshire A, Leech Ret al., Dissociating frontoparietal brain networks with neuroadaptive Bayesian optimization, Nature Communications, Vol: 9, ISSN: 2041-1723

Understanding the unique contributions of frontoparietal networks (FPN) in cognition is challenging because they overlap spatially and are co-activated by diverse tasks. Characterizing these networks therefore involves studying their activation across many different cognitive tasks, which previously was only possible with meta-analyses. Here, we use neuroadaptive Bayesian optimization, an approach combining real-time analysis of functional neuroimaging data with machine-learning, to discover cognitive tasks that segregate ventral and dorsal FPN activity. We identify and subsequently refine two cognitive tasks, Deductive Reasoning and Tower of London, which maximally dissociate the dorsal from ventral FPN. We subsequently investigate these two FPNs in the context of a wider range of FPNs and demonstrate the importance of studying the whole activity profile across tasks to uniquely differentiate any FPN. Our findings deviate from previous meta-analyses and hypothesized functional labels for these FPNs. Taken together the results form the starting point for a neurobiologically-derived cognitive taxonomy.

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Mason SL, Daws RE, Soreq E, Johnson EB, Scahill RI, Tabrizi SJ, Barker RA, Hampshire Aet al., 2018, Predicting clinical diagnosis in Huntington's disease: An imaging polymarker, ANNALS OF NEUROLOGY, Vol: 83, Pages: 532-543, ISSN: 0364-5134

ObjectiveHuntington's disease (HD) gene carriers can be identified before clinical diagnosis; however, statistical models for predicting when overt motor symptoms will manifest are too imprecise to be useful at the level of the individual. Perfecting this prediction is integral to the search for disease modifying therapies. This study aimed to identify an imaging marker capable of reliably predicting real‐life clinical diagnosis in HD.MethodA multivariate machine learning approach was applied to resting‐state and structural magnetic resonance imaging scans from 19 premanifest HD gene carriers (preHD, 8 of whom developed clinical disease in the 5 years postscanning) and 21 healthy controls. A classification model was developed using cross‐group comparisons between preHD and controls, and within the preHD group in relation to “estimated” and “actual” proximity to disease onset. Imaging measures were modeled individually, and combined, and permutation modeling robustly tested classification accuracy.ResultsClassification performance for preHDs versus controls was greatest when all measures were combined. The resulting polymarker predicted converters with high accuracy, including those who were not expected to manifest in that time scale based on the currently adopted statistical models.InterpretationWe propose that a holistic multivariate machine learning treatment of brain abnormalities in the premanifest phase can be used to accurately identify those patients within 5 years of developing motor features of HD, with implications for prognostication and preclinical trials.

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Huntley J, Corbett A, Wesnes K, Brooker H, Stenton R, Hampshire A, Ballard Cet al., 2018, Online assessment of risk factors for dementia and cognitive function in healthy adults., Int J Geriatr Psychiatry, Vol: 33, Pages: e286-e293

OBJECTIVE: Several potentially modifiable risk factors for cognitive decline and dementia have been identified, including low educational attainment, smoking, diabetes, physical inactivity, hypertension, midlife obesity, depression, and perceived social isolation. Managing these risk factors in late midlife and older age may help reduce the risk of dementia; however, it is unclear whether these factors also relate to cognitive performance in older individuals without dementia. METHOD: Data from 14 201 non-demented individuals aged >50 years who enrolled in the online PROTECT study were used to examine the relationship between cognitive function and known modifiable risk factors for dementia. Multivariate regression analyses were conducted on 4 cognitive outcomes assessing verbal and spatial working memory, visual episodic memory, and verbal reasoning. RESULTS: Increasing age was associated with reduced performance across all tasks. Higher educational achievement, the presence of a close confiding relationship, and moderate alcohol intake were associated with benefits across all 4 cognitive tasks, and exercise was associated with better performance on verbal reasoning and verbal working memory tasks. A diagnosis of depression was negatively associated with performance on visual episodic memory and working memory tasks, whereas being underweight negatively affected performance on all tasks apart from verbal working memory. A history of stroke was negatively associated with verbal reasoning and working memory performance. CONCLUSION: Known modifiable risk factors for dementia are associated with cognitive performance in non-demented individuals in late midlife and older age. This provides further support for public health interventions that seek to manage these risk factors across the lifespan.

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Daws RE, Hampshire A, 2017, The reasoning and religiosity is underpinned by a bias for intuitive responses specifically when intuition and logic are in conflict, Frontiers in Psychology, Vol: 8, ISSN: 1664-1078

It is well established that religiosity correlates inversely with intelligence. A prominent hypothesis states that this correlation reflects behavioral biases toward intuitive problem solving, which causes errors when intuition conflicts with reasoning. We tested predictions of this hypothesis by analyzing data from two large-scale Internet-cohort studies (combined N = 63,235). We report that atheists surpass religious individuals in terms of reasoning but not working-memory performance. The religiosity effect is robust across sociodemographic factors including age, education and country of origin. It varies significantly across religions and this co-occurs with substantial cross-group differences in religious dogmatism. Critically, the religiosity effect is strongest for tasks that explicitly manipulate conflict; more specifically, atheists outperform the most dogmatic religious group by a substantial margin (0.6 standard deviations) during a color-word conflict task but not during a challenging matrix-reasoning task. These results support the hypothesis that behavioral biases rather than impaired general intelligence underlie the religiosity effect.

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Fallon SJ, Bor D, Hampshire A, Barker RA, Owen AMet al., 2017, Spatial structure normalises working memory performance in Parkinson's disease., Cortex, Vol: 96, Pages: 73-82

Cognitive deficits are a frequent symptom of Parkinson's disease (PD), particularly in the domain of spatial working memory (WM). Despite numerous demonstrations of aberrant WM in patients, there is a lack of understanding about how, if at all, their WM is fundamentally altered. Most notably, it is unclear whether span - the yardstick upon which most WM models are built - is compromised by the disease. Moreover, it is also unknown whether WM deficits occur in all patients or only exist in a sub-group who are executively impaired. We assessed the factors that influenced spatial span in medicated patients by varying the complexity of to-be-remembered items. Principally, we manipulated the ease with which items could enter - or be blocked from - WM by varying the level of structure in memoranda. Despite having similar levels of executive performance to controls, PD patients were only impaired when remembering information that lacked spatial, easy-to-chunk, structure. Patients' executive function, however, did not influence this effect. The ease with which patients could control WM was further examined by presenting irrelevant information during encoding, varying the level of structure in irrelevant information and manipulating the amount of switching between relevant and irrelevant information. Disease did not significantly alter the effect of these manipulations. Rather, patients' executive performance constrained the detrimental effect of irrelevant information on WM. Thus, PD patients' spatial span is predominantly determined by level of structure in to-be-remembered information, whereas their level of executive function may mitigate against the detrimental effect of irrelevant information.

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Vaghi MM, Hampshire A, Fineberg NA, Kaser M, Brühl AB, Sahakian BJ, Chamberlain SR, Robbins TWet al., 2017, Hypoactivation and Dysconnectivity of a Frontostriatal Circuit During Goal-Directed Planning as an Endophenotype for Obsessive-Compulsive Disorder, Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, Vol: 2, Pages: 655-663, ISSN: 2451-9022

© 2017 Society of Biological Psychiatry Background The symptoms of obsessive-compulsive disorder (OCD) have been postulated to result from impaired executive functioning and excessive habit formation at the expense of goal-directed control and have been objectively demonstrated using neuropsychological tests in such patients. This study tested whether there is functional hypoactivation as well as dysconnectivity of discrete frontostriatal pathways during goal-directed planning in patients with OCD and in their unaffected first-degree relatives. Methods In total, 21 comorbidity-free patients with OCD, 19 clinically asymptomatic first-degree relatives of these patients, and 20 control participants were tested on a functional magnetic resonance optimized version of the Tower of London task. Group differences in brain activation during goal-directed planning were measured together with associated frontostriatal functional connectivity. Results Patients with OCD and their clinically asymptomatic relatives manifested hypoactivation of the right dorsolateral prefrontal cortex during goal-directed planning coupled with reduced functional connectivity between this cortical region and the basal ganglia (putamen). Conclusions Hypoactivation of cortical regions associated with goal-directed planning and associated frontostriatal dysconnectivity represent a candidate endophenotype for OCD. These findings accord with abnormalities in neural networks supporting the balance between goal-directed and habitual behavior, with implications for recent neuropsychological theories of OCD and the major neurobiological model for this disorder.

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Sliwinska M, Ribeiro Violante I, Wise R, Leech R, Devlin J, Geranmayeh F, Hampshire Aet al., 2017, Stimulating Multiple-Demand Cortex Enhances Vocabulary Learning, Journal of Neuroscience, Vol: 37, Pages: 7606-7618, ISSN: 1529-2401

It is well established that domain general networks (DGNs) in the human brain become active when diverse novel skills and behaviors are being learnt. However, their causal role in learning remains to be established. In the present study, we first performed functional magnetic resonance imaging on healthy participants to confirm that DGNs were most active in the initial stages of learning a novel vocabulary, consisting of pronounceable nonwords (pseudowords), each associated with a picture of a real object. We then examined, in healthy participants, whether repetitive transcranial magnetic stimulation of a frontal midline node of the cingulo-opercular DGN affected learning rates during the initial stages of learning. We report that stimulation of this node, but not a control brain region, substantially improved both accuracy and response times during the earliest stage of learning pseudowords-object associations. This stimulation had no effect on the processing of established vocabulary, tested by the accuracy and response times when participants decided whether a real word was accurately paired with a picture of an object. These results provide evidence that non-invasive stimulation to DGN nodes can enhance learning rates, thereby demonstrating their causal role in the learning process. We propose that this causal role makes DGNs candidate targets for experimental therapeutics; for example, in stroke patients with aphasia attempting to reacquire a vocabulary.

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Gruszka A, Hampshire A, Barker RA, Owen AMet al., 2017, Normal aging and Parkinson's disease are associated with the functional decline of distinct frontal-striatal circuits., Cortex, Vol: 93, Pages: 178-192

Impaired ability to shift attention between stimuli (i.e. shifting attentional 'set') is a well-established part of the dysexecutive syndrome in Parkinson's Disease (PD), nevertheless cognitive and neural bases of this deficit remain unclear. In this study, an fMRI-optimised variant of a classic paradigm for assessing attentional control (Hampshire and Owen 2006) was used to contrast activity in dissociable executive circuits in early-stage PD patients and controls. The results demonstrated that the neural basis of the executive performance impairments in PD is accompanied by hypoactivation within the striatum, anterior cingulate cortex (vACC), and inferior frontal sulcus (IFS) regions. By contrast, in aging it is associated with hypoactivation of the anterior insula/inferior frontal operculum (AI/FO) and the pre-supplementary motor area (preSMA). Between group behavioural differences were also observed; whereas normally aging individuals exhibited routine-problem solving deficits, PD patients demonstrated more global task learning deficits. These findings concur with recent research demonstrating model-based reinforcement learning deficits in PD and provide evidence that the AI/FO and IFS circuits are differentially impacted by PD and normal aging.

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Huntley JD, Hampshire A, Bor D, Owen AM, Howard RJet al., 2017, The importance of sustained attention in early Alzheimer's disease., Int J Geriatr Psychiatry, Vol: 32, Pages: 860-867

INTRODUCTION: There is conflicting evidence regarding impairment of sustained attention in early Alzheimer's disease (AD). We examine whether sustained attention is impaired and predicts deficits in other cognitive domains in early AD. METHODS: Fifty-one patients with early AD (MMSE > 18) and 15 healthy elderly controls were recruited. The sustained attention to response task (SART) was used to assess sustained attention. A subset of 25 patients also performed tasks assessing general cognitive function (ADAS-Cog), episodic memory (Logical memory scale, Paired Associates Learning), executive function (verbal fluency, grammatical reasoning) and working memory (digit and spatial span). RESULTS: AD patients were significantly impaired on the SART compared to healthy controls (total error β = 19.75, p = 0.027). SART errors significantly correlated with MMSE score (Spearman's rho = -0.338, p = 0.015) and significantly predicted deficits in ADAS-Cog (β = 0.14, p = 0.004). DISCUSSIONS: Patients with early AD have significant deficits in sustained attention, as measured using the SART. This may impair performance on general cognitive testing, and therefore should be taken into account during clinical assessment, and everyday management of individuals with early AD. Copyright © 2016 John Wiley & Sons, Ltd.

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Metzler-Baddeley C, Foley S, de Santis S, Charron C, Hampshire A, Caeyenberghs K, Jones DKet al., 2017, Dynamics of white matter plasticity underlying working memory training: multimodal evidence from diffusion MRI and relaxometry, Journal of Cognitive Neuroscience, Vol: 29, Pages: 1509-1520, ISSN: 0898-929X

Adaptive working memory (WM) training may lead to cognitive benefits that are associated with white matter plasticity in parietofrontal networks, but the underlying mechanisms remain poorly understood. We investigated white matter microstructural changes after adaptive WM training relative to a nonadaptive comparison group. Microstructural changes were studied in the superior longitudinal fasciculus, the main parietofrontal connection, and the cingulum bundle as a comparison pathway. MRI-based metrics were the myelin water fraction and longitudinal relaxation rate R1 from multicomponent relaxometry (captured with the mcDESPOT approach) as proxy metrics of myelin, the restricted volume fraction from the composite hindered and restricted model of diffusion as an estimate of axon morphology, and fractional anisotropy and radial diffusivity from diffusion tensor imaging. PCA was used for dimensionality reduction. Adaptive training was associated with benefits in a “WM capacity” component and increases in a microstructural component (increases in R1, restricted volume fraction, fractional anisotropy, and reduced radial diffusivity) that predominantly loaded on changes in the right dorsolateral superior longitudinal fasciculus and the left parahippocampal cingulum. In contrast, nonadaptive comparison activities were associated with the opposite pattern of reductions in WM capacity and microstructure. No group differences were observed for the myelin water fraction metric suggesting that R1 was a more sensitive “myelin” index. These results demonstrate task complexity and location-specific white matter microstructural changes that are consistent with tissue alterations underlying myelination in response to training.

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Geranmayeh F, Wing Chau T, Wise RJS, Leech R, Hampshire Aet al., 2017, Domain-general subregions of the medial prefrontal cortex contribute to recovery of language after stroke, Brain, Vol: 140, Pages: 1947-1958, ISSN: 1460-2156

We hypothesized that the recovery of speech production after left hemisphere stroke not only depends on the integrity of language-specialized brain systems, but also on ‘domain-general’ brain systems that have much broader functional roles. The presupplementary motor area/dorsal anterior cingulate forms part of the cingular-opercular network, which has a broad role in cognition and learning. Consequently, we have previously suggested that variability in the recovery of speech production after aphasic stroke may relate in part to differences in patients’ abilities to engage this domain-general brain region. To test our hypothesis, 27 patients (aged 59 ± 11 years) with a left hemisphere stroke performed behavioural assessments and event-related functional magnetic resonance imaging tasks at two time points; first in the early phase (∼2 weeks) and then ∼4 months after the ictus. The functional magnetic resonance imaging tasks were designed to differentiate between activation related to language production (sentential overt speech production—Speech task) and activation related to cognitive processing (non-verbal decision making). Simple rest and counting conditions were also included in the design. Task-evoked regional brain activations during the early and late phases were compared with a longitudinal measure of recovery of language production. In accordance with a role in cognitive processing, substantial activity was observed within the presupplementary motor area/dorsal anterior cingulate during the decision-making task. Critically, the level of activation within this region during speech production correlated positively with the longitudinal recovery of speech production across the two time points (as measured by the in-scanner performance in the Speech task). This relationship was observed for activation in both the early phase (r = 0.363, P = 0.03 one-tailed) and the late phase (r = 0.538, P = 0.004). Furthermore, presupplem

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Huntley JD, Hampshire A, Bor D, Owen A, Howard RJet al., 2017, Adaptive working memory strategy training in early Alzheimer's disease: randomised controlled trial, BRITISH JOURNAL OF PSYCHIATRY, Vol: 210, Pages: 61-66, ISSN: 0007-1250

JOURNAL ARTICLE

Hampshire A, 2017, A Functional Network Perspective on the Role of the Frontal Lobes in Executive Cognition, Executive Functions in Health and Disease, Editors: Goldberg, Publisher: Elsevier, Pages: 71-100

BOOK CHAPTER

Li L, Violante I, Ross E, Leech R, Hampshire A, Carmichael D, Sharp Det al., 2016, BRAIN NETWORK MODULATION WITH NON-INVASIVE BRAIN STIMULATION, Annual Meeting of the Association-of-British-Neurologists (ABN), Publisher: BMJ PUBLISHING GROUP, ISSN: 0022-3050

CONFERENCE PAPER

Connell L, Daws R, Hampshire A, Nicholas R, Raffel Jet al., 2016, Validating a participant-led computerised cognitive battery in people with multiple sclerosis, 32nd Congress of the European-Committee-for-Treatment-and-Research-in-Multiple-Sclerosis (ECTRIMS), Publisher: SAGE PUBLICATIONS LTD, Pages: 140-141, ISSN: 1352-4585

CONFERENCE PAPER

Matthews PM, Hampshire A, 2016, Clinical concepts emerging from fMRI functional connectomics, Neuron, Vol: 91, Pages: 511-528, ISSN: 0896-6273

Recent advances in connectomics have led to a synthesis of perspectives regarding the brain's functional organization that reconciles classical concepts of localized specialization with an appreciation for properties that emerge from interactions across distributed functional networks. This provides a more comprehensive framework for understanding neural mechanisms of normal cognition and disease. Although fMRI has not become a routine clinical tool, research has already had important influences on clinical concepts guiding diagnosis and patient management. Here we review illustrative examples. Studies demonstrating the network plasticity possible in adults and the global consequences of even focal brain injuries or disease both have had substantial impact on modern concepts of disease evolution and expression. Applications of functional connectomics in studies of clinical populations are challenging traditional disease classifications and helping to clarify biological relationships between clinical syndromes (and thus also ways of extending indications for, or "re-purposing," current treatments). Large datasets from prospective, longitudinal studies promise to enable the discovery and validation of functional connectomic biomarkers with the potential to identify people at high risk of disease before clinical onset, at a time when treatments may be most effective. Studies of pain and consciousness have catalyzed reconsiderations of approaches to clinical management, but also have stimulated debate about the clinical meaningfulness of differences in internal perceptual or cognitive states inferred from functional connectomics or other physiological correlates. By way of a closing summary, we offer a personal view of immediate challenges and potential opportunities for clinically relevant applications of fMRI-based functional connectomics.

JOURNAL ARTICLE

Fallon SJ, Hampshire A, Barker RA, Owen AMet al., 2016, Learning to be inflexible: Enhanced attentional biases in Parkinson's disease., Cortex, Vol: 82, Pages: 24-34

Impaired attentional flexibility is considered to be one of the core cognitive deficits in Parkinson's disease (PD). However, the mechanisms that underlie this impairment are contested. Progress in resolving this dispute has also been hindered by the fact that cognitive deficits in PD are heterogeneous; therefore, it is unclear whether attentional impairments are only present in a subgroup of patients. Here, we demonstrate that what differentiates PD patients from age-matched controls is an inability to shift attention away from previously relevant information (perseveration) and an inability to shift attention towards previously irrelevant information (learned irrelevance). In contrast, there was no evidence that PD patients, compared to controls, were impaired in being able to appropriately attend to, or ignore, novel information. Furthermore, when patients were stratified according to their level of executive impairment, the executively impaired group showed a selective deficit in set formation compared to the unimpaired group, a behavioural pattern reminiscent of cortical dopamine depletion. Cumulatively, these results suggest that cognitive inflexibility in PD relates to a specific form of attentional dysfunction, in which learned attentional biases cannot be overcome.

JOURNAL ARTICLE

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

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