John Done - Profile on Academia.edu (original) (raw)
Papers by John Done
Personal Correspondence
In handwriting the drawing or copying of an individual letter involves a process of linearising w... more In handwriting the drawing or copying of an individual letter involves a process of linearising whereby the form of the letter is broken down into a temporal sequence of strokes for production. In experienced writers, letters are produced consistently using the same production methods that are economic in terms of movement. This regularity permits a rule-based description of such production processes, which can be used in the teaching of handwriting skills. In this paper, the outstanding question from rule-based descriptions as to how consistent and stable letter production behaviour emerges as a product of practice and experience is addressed through the implementation of a connectionist model of sequential letter production. This model: (1) examines the emergence of letter production behaviour, namely- the linearising process, (2) explores how letters may be internally represented across both spatial and temporal dimensions, and (3) investigates the impact of learning certain lett...
Rheumatoid arthritis – prognosis, predictors and outcome, 2018
AB0216-Table 1 REFERENCES: [1] Iacono D, et al. Mortality in Italian patients with rheumatoid art... more AB0216-Table 1 REFERENCES: [1] Iacono D, et al. Mortality in Italian patients with rheumatoid arthritis: evidence for a low mortality rate from cancer and infections in patients followed up at a tertiary center. Open Access Rheumatol 2017. [2] Ajeganova S, et al. Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts. Ann Rheum Dis 2016. [3] Vidal-Bralo L, et al. Anti-carbamylated protein autoantibodies associated with mortality in Spanish rheumatoid arthritis patients. PLoS One 2017.
Schizophrenia Research, 2008
Background: Risperidone long-acting injectable (RLAI) is the only long-acting atypical antipsycho... more Background: Risperidone long-acting injectable (RLAI) is the only long-acting atypical antipsychotic. According to expert opinion it is used in late treatment stage for high risk noncompliant patients in 73
![Research paper thumbnail of BHPR: Research [278-290]: 278. What does the Hospital Anxiety and Depression Scale Measure? Evidence of a Bifactor Structure and Item Bias](https://attachments.academia-assets.com/96852329/thumbnails/1.jpg)
](Rheumatology, 2010
Background: The Hospital Anxiety and Depression Scale (HADS) is a commonly used measure of psycho... more Background: The Hospital Anxiety and Depression Scale (HADS) is a commonly used measure of psychological distress in patient populations. The HADS was designed to measure two correlated anxiety and depression factors, however previous research is inconclusive finding support for several alternative models. In addition, some items may be biased by the somatic features of a disease. Currently there are no published studies considering item bias in rheumatological patients. The objective of this study was to (1) examine the factor structure of the HADS and (2) assess for the presence of item bias. Methods: The sample consisted of 160 patients attending one of the Early Rheumatoid Arthritis Study centres, for whom individual HADS item responses were available. All completed questionnaires were pooled resulting in a total sample of 1728. Alternative models were compared using confirmatory factor analysis. Item bias was assessed by examining relation between individual HADS items and covariates (disease duration, age, sex, HAQ, DAS and pain) whilst controlling for underlying level of psychological distress. Results: Superior fit was observed for a bifactor structure (2(20) ¼ 87, RMSEA ¼ 0.04, CFI ¼ 0.97, TLI ¼ 0.99), indicating that the HADS taps into a general psychological distress factor as well as specific anxiety and depression factors. The HADS anxiety and depression scores correlated highly with the respective specific factor but even more so with the general factor (HADS-A: r(anxiety) ¼ 0.59, r(general) ¼ 0.86; HADS-D: r(depression) ¼ 0.64, r(general) ¼ 0.83). Item bias was observed for item D8 ''I feel slowed down'' with individuals with same underlying level of psychological distress but worse disability (b ¼ 0.34, P < 0.001) and higher disease activity (b ¼ 0.13, P < 0.001) more likely to respond positively to the item. Further item bias was observed for item D14 ''I can enjoy a good book or radio or TV programme'' with females less likely to respond positively to the item than males with the same level of psychological distress (b ¼-0.50, P < 0.001). However, the magnitude of the bias was small and controlling for it made no substantive difference in the association between the covariates and psychological distress factors. Conclusions: The HADS total score may be used as an assessment of general psychological distress, incorporating specific features of anxiety and depression. However, factor scores, which can be calculated using a simple tool provided by the author, may provide greater insight into an individual's psychological well-being, by allowing for the assessment of anxiety and depression separately. Although item bias was observed, it is unlikely to have a substantive effect.
Does religious belief enable positive interpretation of auditory hallucinations? A comparison of religious voice hearers with and without psychosis
Cognitive Neuropsychiatry, 2011
Introduction. Hearing voices occurs in people without psychosis. Why hearing voices is such a key... more Introduction. Hearing voices occurs in people without psychosis. Why hearing voices is such a key pathological feature of psychosis whilst remaining a manageable experience in nonpsychotic people is yet to be understood. We hypothesised that religious voice hearers would interpret voices in accordance with their beliefs and therefore experience less distress. Methods. Three voice hearing groups, which comprised: 20 mentally healthy Christians, 15 Christian patients with psychosis, and 14 nonreligious patients with psychosis. All completed (1) questionnaires with rating scales measuring the perceptual and emotional aspects of hallucinated voices, and (2) a semistructured interview to explore whether religious belief is used to make sense of the voice hearing experience. Results. The three groups had perceptually similar experiences when hearing the voices. Mentally healthy Christians appeared to assimilate the experience with their religious beliefs (schematic processing) resulting in positive interpretations. Christian patients tended not to assimilate the experience with their religious beliefs, frequently reporting nonreligious interpretations that were predominantly negative. Nearly all participants experienced voices as powerful, but mentally healthy Christians reported the power of voices positively. Conclusion. Religious belief appeared to have a profound, beneficial influence on the mentally healthy Christians&amp;amp;amp;#39; interpretation of hearing voices, but had little or no influence in the case of Christian patients.
Correspondence to
of young people toward driving after smoking cannabis or after
Clinical and experimental rheumatology, 2019
OBJECTIVES The 5-item Compliance Questionnaire for Rheumatology (CQR5) proved reliability and val... more OBJECTIVES The 5-item Compliance Questionnaire for Rheumatology (CQR5) proved reliability and validity in respect of identification of patients likely to be high adherers (HAs) to anti-rheumatic treatment, or low adherers (LAs), i.e. taking<80% of their medications correctly. The objective of the study was to validate an Italian version of CQR5 (I-CQR5) in rheumatoid arthritis (RA) patients and to investigate factors associated with high adherence. METHODS RA patients, undergoing treatment with ≥1 self-administered conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) or biological DMARD (bDMARD), were enrolled. The cross-cultural adaptation and validation of I-CQR5 followed standardised guidelines. I-CQR5 was completed by patients on one occasion. Data were subjected to factor analysis and Partial Credit model Parametrisation (PCM) to assess construct validity of I-CQR5. Analysis of factors associated with high adherence included demographic, social, clinical an...
Does dopamine code for uncertainty (Fiorillo, Tobler & Schultz, 2003; 2005) or is the sustained a... more Does dopamine code for uncertainty (Fiorillo, Tobler & Schultz, 2003; 2005) or is the sustained activation recorded from dopamine neurons a result of Temporal Difference (TD) backpropagating errors (Niv, Duff & Dayan, 2005)? An answer to this question could result in a better understanding of the nature of dopamine signaling, with implications for cognitive disorders, like Schizophrenia. A computer simulation of uncertainty incorporating TD Learning successfully modelled a Reinforcement Learning paradigm and the detailed effects demonstrated in single dopamine neuron recordings by Fiorillo et al. This alternate model provides further evidence that the sustained increase seen in dopamine firing, during uncertainty, is a result of averaging firing from dopamine neurons across trials, and is not normally found within individual trials, supporting the claims of Niv and colleagues.
A review of the current dopamine theories of schizophrenia reveals a likely imbalance between cor... more A review of the current dopamine theories of schizophrenia reveals a likely imbalance between cortical and subcortical microcircuits due to an insufficient inhibitory brake, leading to a disruption of the dopamine system and the classic positive psychotic symptoms, negative symptoms and cognitive deficits associated with the disorder. Recent computational models have modelled the role of dopamine as a reward prediction error, using Temporal Difference and have successfully shown how these symptoms could arise from a disturbance to the dopamine system. We review these models in the light of dopamine theories of schizophrenia and highlight some of the major points that should be addressed by future computational models.
Lecture Notes in Computer Science
The work outlined in this paper explores the influence of prior knowledge and related experience ... more The work outlined in this paper explores the influence of prior knowledge and related experience (held in the form of weights) on the generalisation performance of connectionist models. Networks were trained on simple classification and associated tasks. Results regarding the transfer of related experience between networks trained using backpropagation and recurrent networks performing sequence production, are reported. In terms of prior knowledge, results demonstrate that experienced networks produced their most pronounced generalisation performance advantage over naïve networks when a specific point of difficulty during learning was identified and an incremental training strategy applied at this point. Interestingly, the second set of results showed that knowledge learnt about in one task could be used to facilitate learning of a different but related task. However, in the third experiment, when the network architecture was changed, prior knowledge did not provide any advantage and indeed when learning was expanded, even found to deteriorated.
Rheumatology, 2010
factors. It is now becoming clear that, despite the apparent clinical and phenotypic differences ... more factors. It is now becoming clear that, despite the apparent clinical and phenotypic differences of the autoimmune diseases, they share a number of genetic risk factors. Of note there has been overlap between type 1 diabetes (T1D) and celiac disease (CD). Many of these loci are also susceptibility loci for rheumatoid arthritis (RA). There is already strong evidence suggesting that JIA shares many susceptibility loci with other autoimmune diseases, such as rheumatoid arthritis (RA), type 1 diabetes and multiple sclerosis (MS). Therefore the aim of this study was to test SNPs robustly associated with T1D or CD in a large cohort of JIA cases and controls to investigate the overlap between these diseases. Methods: Sixteen SNPs that showed robust association (P < 5 x 10-7) with T1D and CD and had not been investigated previously in JIA were genotyped in JIA cases (n ¼ 1054) and healthy controls (n ¼ 3129). Genotype and allele frequencies were compared between cases with JIA and controls using the Cochrane-Armitage trend test implemented in PLINK and allelic odds ratios (ORs) and their 95% confidence intervals (CIs) calculated. Results: One SNP in the Lim domain containing preferred translocation partner in lipoma (LPP) gene showed significant association with JIA (ptrend ¼ 0.002 OR 1.18 95% CI 1.06-1.30). A second SNP, rs653178, in ATXN2 showed a trend towards association with JIA however this was not significant after correction for multiple testing (ptrend ¼ 0.02 OR 1.13 95% CI 1.02-1.25). SNPs in this region, have previously shown evidence for association with JIA in a US cohort. A SNP, rs17810546, in IL12A showed a significant allele frequency difference (P ¼ 0.03) between the subtypes and this was driven by a strong association with enthesitis related arthritis (ERA) subtype (ptrend ¼ 0.005 OR 1.88 95% CI 1.2-2.94). Conclusions: We present evidence for a novel JIA susceptibility locus, LPP. LPP has a number of known functions including cell migration and adhesion, has transcriptional activation capacity and has recently been identified as a substrate of protein-tyrosine phosphatase 1B. We present confirmatory evidence for association of the SH2B3/ATXN2/ c12orf30 region with JIA. In addition we identify a subtype specific association of IL12A with ERA. All findings will require validation in independent JIA data sets. Acknowledgements: Childhood arthritis prospective study (CAPS), UKRAG consortium and BSPAR study group. Disclosure statement: All authors have declared no conflicts of interest.
Running Title: pragmatic use of language in pre-morbid adolescents Abstract At eleven years of ag... more Running Title: pragmatic use of language in pre-morbid adolescents Abstract At eleven years of age all children in a UK national birth cohort wrote short stories about the life they expected to be leading at age 25. Using a data linkage exercise, we identified those who later developed schizophrenia , affective psychosis , or other non-psychotic psychiatric disorders in later life based on the PSE CATEGO diagnostic system. The majority of these had completed the written essays. Controls from the reference population were selected , matched for gender, IQ and social and economic status. The essays were scored using well established methods for assessing pragmatic use of language, namely narrative coherence and linguistic cohesion. We hypothesised that children pre-morbid for schizophrenia (Pre-Scz) would obtain low scores on all these measures. However this general hypothesis was largely disproved by the data, although some unpredicted gender effects were found. It is concluded that ...
factors. It is now becoming clear that, despite the apparent clinical and phenotypic differences ... more factors. It is now becoming clear that, despite the apparent clinical and phenotypic differences of the autoimmune diseases, they share a number of genetic risk factors. Of note there has been overlap between type 1 diabetes (T1D) and celiac disease (CD). Many of these loci are also susceptibility loci for rheumatoid arthritis (RA). There is already strong evidence suggesting that JIA shares many susceptibility loci with other autoimmune diseases, such as rheumatoid arthritis (RA), type 1 diabetes and multiple sclerosis (MS). Therefore the aim of this study was to test SNPs robustly associated with T1D or CD in a large cohort of JIA cases and controls to investigate the overlap between these diseases. Methods: Sixteen SNPs that showed robust association (P < 5 x 10-7) with T1D and CD and had not been investigated previously in JIA were genotyped in JIA cases (n ¼ 1054) and healthy controls (n ¼ 3129). Genotype and allele frequencies were compared between cases with JIA and controls using the Cochrane-Armitage trend test implemented in PLINK and allelic odds ratios (ORs) and their 95% confidence intervals (CIs) calculated. Results: One SNP in the Lim domain containing preferred translocation partner in lipoma (LPP) gene showed significant association with JIA (ptrend ¼ 0.002 OR 1.18 95% CI 1.06-1.30). A second SNP, rs653178, in ATXN2 showed a trend towards association with JIA however this was not significant after correction for multiple testing (ptrend ¼ 0.02 OR 1.13 95% CI 1.02-1.25). SNPs in this region, have previously shown evidence for association with JIA in a US cohort. A SNP, rs17810546, in IL12A showed a significant allele frequency difference (P ¼ 0.03) between the subtypes and this was driven by a strong association with enthesitis related arthritis (ERA) subtype (ptrend ¼ 0.005 OR 1.88 95% CI 1.2-2.94). Conclusions: We present evidence for a novel JIA susceptibility locus, LPP. LPP has a number of known functions including cell migration and adhesion, has transcriptional activation capacity and has recently been identified as a substrate of protein-tyrosine phosphatase 1B. We present confirmatory evidence for association of the SH2B3/ATXN2/ c12orf30 region with JIA. In addition we identify a subtype specific association of IL12A with ERA. All findings will require validation in independent JIA data sets. Acknowledgements: Childhood arthritis prospective study (CAPS), UKRAG consortium and BSPAR study group. Disclosure statement: All authors have declared no conflicts of interest.
A Model of Dopamine and Uncertainty Using Temporal Difference Angela J. Thurnham* (a.j.thurnham@h... more A Model of Dopamine and Uncertainty Using Temporal Difference Angela J. Thurnham* (a.j.thurnham@herts.ac.uk), D. John Done** (d.j.done@herts.ac.uk), Neil Davey* (n.davey@herts.ac.uk), Ray J. Frank* (r.j.frank@herts.ac.uk) School of Computer Science,* School of Psychology, **University of Hertfordshire, College Lane, Hatfield, Hertfordshire. AL10 9AB United Kingdom from their electrophysiological characteristics, during a delay paradigm of classical conditioning to receive a fixed juice reward, while manipulating the probability of receipt of the reward. Two related but distinct parameters of reward were identified from the activation produced, after learning had taken place: (i) A phasic burst of activity, or reward prediction error, at the time of the expected reward, whose magnitude increased as probability decreased; and (ii) a new slower, sustained activity, above baseline, related to motivationally relevant stimuli, which developed with increasing levels of uncertainty, and var...
A Connectionist Model of the Role of Dopamine in Incentive Salience and Temporal Difference learn... more A Connectionist Model of the Role of Dopamine in Incentive Salience and Temporal Difference learning Angela J. Thurnham* (a.j.thurnham@herts.ac.uk), D. John Done** (d.j.done@herts.ac.uk), Neil Davey* (n.davey@herts.ac.uk), Ray J. Frank* (r.j.frank@herts.ac.uk) School of Computer Science,* School of Psychology, **University of Hertfordshire, College Lane, Hatfield, Hertfordshire. AL10 9AB England Dopamine as a Prediction Error (PE) Signal in Reinforcement Learning Dopamine is a neurotransmitter and disruption to this system has long been associated with the neuropsychiatric disorder, schizophrenia. Current theories of the effects of dopamine on behaviour focus on the role of dopamine in Reinforcement Learning, where organisms learn to organise their behaviour under the influence of goals, and expected future reward is believed to drive action selection. Reward Prediction Hypothesis Schultz and colleagues have demonstrated that dopamine neurons in the midbrain regions are particularly...
Research data supporting "Interpretation of published meta-analytical studies affected by implementation errors in the GingerALE software
An interpretative phenomenological analysis of service users’ experiences in a psychosocial addictions intervention
Psychology and Psychotherapy: Theory, Research and Practice
Archives of Neuropsychiatry
Introduction: Previous studies showed that over the course of learning many neurons in the medial... more Introduction: Previous studies showed that over the course of learning many neurons in the medial prefrontal cortex adapt their firing rate towards the options with highest predicted value reward but it was showed that during later learning trials the brain switches to a more automatic processing mode governed by the basal ganglia. Based on this evidence, we hypothesized that during the early learning trials the predicted values of chosen options will be coded by a goal directed system in the medial frontal cortex but during the late trials the predicted values will be coded by the habitual learning system in the dorsal striatum. Methods: In this study, using a 3 Tesla functional magnetic resonance imaging scanner (fMRI), blood oxygen level dependent signal (BOLD) data was collected whilst participants (N=12) performed a reinforcement learning task. The task consisted of instrumental conditioning trials wherein each trial a participant choose one of the two available options in order to win or avoid losing money. In addition to that, depending on the experimental condition, participants received either monetary reward (gain money), monetary penalty (lose money) or neural outcome. Results: Using model-based analysis for functional magnetic resonance imaging (fMRI) event related designs; region of interest (ROI) analysis was performed to nucleus accumbens, medial frontal cortex, caudate nucleus, putamen and globus pallidus internal and external segments. In order to compare the difference in brain activity for early (goal directed) versus late learning (habitual, automatic) trials, separate ROI analyses were performed for each anatomical sub-region. For the reward condition, we found significant activity in the medial frontal cortex (p<0.05) only for early learning trials but activity is shifted to bilateral putamen (p<0.05) during later trials. However, for the loss condition no significant activity was found for early trials except globus pallidus internal segment showed a significant activity (p<0.05) for later trials. Conclusion: We found that during reinforcement learning activation in the brain shifted from the medial frontal regions to dorsal regions of the striatum. These findings suggest that there are two separable (early goal directed and late habitual) learning systems in the brain.
Brain Sciences
Reinforcement learning studies in rodents and primates demonstrate that goal-directed and habitua... more Reinforcement learning studies in rodents and primates demonstrate that goal-directed and habitual choice behaviors are mediated through different fronto-striatal systems, but the evidence is less clear in humans. In this study, functional magnetic resonance imaging (fMRI) data were collected whilst participants (n = 20) performed a conditional associative learning task in which blocks of novel conditional stimuli (CS) required a deliberate choice, and blocks of familiar CS required an intuitive choice. Using standard subtraction analysis for fMRI event-related designs, activation shifted from the dorso-fronto-parietal network, which involves dorsolateral prefrontal cortex (DLPFC) for deliberate choice of novel CS, to ventro-medial frontal (VMPFC) and anterior cingulate cortex for intuitive choice of familiar CS. Supporting this finding, psycho-physiological interaction (PPI) analysis, using the peak active areas within the PFC for novel and familiar CS as seed regions, showed funct...
Neurological Sciences and Neurophysiology
Functional imaging studies offer alternative explanations for the neural correlates of monetary g... more Functional imaging studies offer alternative explanations for the neural correlates of monetary gain and loss related brain activity, and their opponents, omission of gains and losses. One possible explanation based on the psychology of opponent process theory suggests that successful avoidance of an aversive outcome is itself rewarding, and hence activates brain regions involved in reward processing. In order to test this hypothesis, we compared brain activation for successful avoidance of losses and receipt of monetary gains. Additionally, the brain regions involved in processing of frustrative neutral outcomes and actual losses were compared in order to test whether these two representations are coded in common or distinct brain regions. Methods: Using a 3 Tesla functional magnetic resonance imaging machine, fifteen healthy volunteers between the ages 22 to 28 were scanned for blood oxygen level dependent signal changes while they were performing a probabilistic learning task, wherein each trial a participant chose one of the two available options in order to win or avoid losing money. Results: The results confirmed, previous findings showing that medial frontal cortex and ventral striatum show significant activation (p<0.001) not only for monetary gains but also for successful avoidance of losses. A similar activation pattern was also observed for monetary losses and avoidance of gains in the medial frontal cortex, and posterior cingulate cortex, however, there was increased activation in amygdala specific to monetary losses (p<0.001). Further, subtraction analysis showed that regardless of the type of loss (i.e., frustrative neutral outcomes) posterior insula showed increased activation. Conclusion: This study provides evidence for a significant overlap not only between gains and losses, but also between their opponents. The results suggested that the overlapping activity pattern in the medial frontal cortex could be explained by a more abstract function of medial frontal cortex, such as outcome evaluation or performance monitoring, which possibly does not differentiate between winning and losing monetary outcomes.
Personal Correspondence
In handwriting the drawing or copying of an individual letter involves a process of linearising w... more In handwriting the drawing or copying of an individual letter involves a process of linearising whereby the form of the letter is broken down into a temporal sequence of strokes for production. In experienced writers, letters are produced consistently using the same production methods that are economic in terms of movement. This regularity permits a rule-based description of such production processes, which can be used in the teaching of handwriting skills. In this paper, the outstanding question from rule-based descriptions as to how consistent and stable letter production behaviour emerges as a product of practice and experience is addressed through the implementation of a connectionist model of sequential letter production. This model: (1) examines the emergence of letter production behaviour, namely- the linearising process, (2) explores how letters may be internally represented across both spatial and temporal dimensions, and (3) investigates the impact of learning certain lett...
Rheumatoid arthritis – prognosis, predictors and outcome, 2018
AB0216-Table 1 REFERENCES: [1] Iacono D, et al. Mortality in Italian patients with rheumatoid art... more AB0216-Table 1 REFERENCES: [1] Iacono D, et al. Mortality in Italian patients with rheumatoid arthritis: evidence for a low mortality rate from cancer and infections in patients followed up at a tertiary center. Open Access Rheumatol 2017. [2] Ajeganova S, et al. Anticitrullinated protein antibodies and rheumatoid factor are associated with increased mortality but with different causes of death in patients with rheumatoid arthritis: a longitudinal study in three European cohorts. Ann Rheum Dis 2016. [3] Vidal-Bralo L, et al. Anti-carbamylated protein autoantibodies associated with mortality in Spanish rheumatoid arthritis patients. PLoS One 2017.
Schizophrenia Research, 2008
Background: Risperidone long-acting injectable (RLAI) is the only long-acting atypical antipsycho... more Background: Risperidone long-acting injectable (RLAI) is the only long-acting atypical antipsychotic. According to expert opinion it is used in late treatment stage for high risk noncompliant patients in 73
Rheumatology, 2010
Background: The Hospital Anxiety and Depression Scale (HADS) is a commonly used measure of psycho... more Background: The Hospital Anxiety and Depression Scale (HADS) is a commonly used measure of psychological distress in patient populations. The HADS was designed to measure two correlated anxiety and depression factors, however previous research is inconclusive finding support for several alternative models. In addition, some items may be biased by the somatic features of a disease. Currently there are no published studies considering item bias in rheumatological patients. The objective of this study was to (1) examine the factor structure of the HADS and (2) assess for the presence of item bias. Methods: The sample consisted of 160 patients attending one of the Early Rheumatoid Arthritis Study centres, for whom individual HADS item responses were available. All completed questionnaires were pooled resulting in a total sample of 1728. Alternative models were compared using confirmatory factor analysis. Item bias was assessed by examining relation between individual HADS items and covariates (disease duration, age, sex, HAQ, DAS and pain) whilst controlling for underlying level of psychological distress. Results: Superior fit was observed for a bifactor structure (2(20) ¼ 87, RMSEA ¼ 0.04, CFI ¼ 0.97, TLI ¼ 0.99), indicating that the HADS taps into a general psychological distress factor as well as specific anxiety and depression factors. The HADS anxiety and depression scores correlated highly with the respective specific factor but even more so with the general factor (HADS-A: r(anxiety) ¼ 0.59, r(general) ¼ 0.86; HADS-D: r(depression) ¼ 0.64, r(general) ¼ 0.83). Item bias was observed for item D8 ''I feel slowed down'' with individuals with same underlying level of psychological distress but worse disability (b ¼ 0.34, P < 0.001) and higher disease activity (b ¼ 0.13, P < 0.001) more likely to respond positively to the item. Further item bias was observed for item D14 ''I can enjoy a good book or radio or TV programme'' with females less likely to respond positively to the item than males with the same level of psychological distress (b ¼-0.50, P < 0.001). However, the magnitude of the bias was small and controlling for it made no substantive difference in the association between the covariates and psychological distress factors. Conclusions: The HADS total score may be used as an assessment of general psychological distress, incorporating specific features of anxiety and depression. However, factor scores, which can be calculated using a simple tool provided by the author, may provide greater insight into an individual's psychological well-being, by allowing for the assessment of anxiety and depression separately. Although item bias was observed, it is unlikely to have a substantive effect.
Does religious belief enable positive interpretation of auditory hallucinations? A comparison of religious voice hearers with and without psychosis
Cognitive Neuropsychiatry, 2011
Introduction. Hearing voices occurs in people without psychosis. Why hearing voices is such a key... more Introduction. Hearing voices occurs in people without psychosis. Why hearing voices is such a key pathological feature of psychosis whilst remaining a manageable experience in nonpsychotic people is yet to be understood. We hypothesised that religious voice hearers would interpret voices in accordance with their beliefs and therefore experience less distress. Methods. Three voice hearing groups, which comprised: 20 mentally healthy Christians, 15 Christian patients with psychosis, and 14 nonreligious patients with psychosis. All completed (1) questionnaires with rating scales measuring the perceptual and emotional aspects of hallucinated voices, and (2) a semistructured interview to explore whether religious belief is used to make sense of the voice hearing experience. Results. The three groups had perceptually similar experiences when hearing the voices. Mentally healthy Christians appeared to assimilate the experience with their religious beliefs (schematic processing) resulting in positive interpretations. Christian patients tended not to assimilate the experience with their religious beliefs, frequently reporting nonreligious interpretations that were predominantly negative. Nearly all participants experienced voices as powerful, but mentally healthy Christians reported the power of voices positively. Conclusion. Religious belief appeared to have a profound, beneficial influence on the mentally healthy Christians&amp;amp;amp;#39; interpretation of hearing voices, but had little or no influence in the case of Christian patients.
Correspondence to
of young people toward driving after smoking cannabis or after
Clinical and experimental rheumatology, 2019
OBJECTIVES The 5-item Compliance Questionnaire for Rheumatology (CQR5) proved reliability and val... more OBJECTIVES The 5-item Compliance Questionnaire for Rheumatology (CQR5) proved reliability and validity in respect of identification of patients likely to be high adherers (HAs) to anti-rheumatic treatment, or low adherers (LAs), i.e. taking<80% of their medications correctly. The objective of the study was to validate an Italian version of CQR5 (I-CQR5) in rheumatoid arthritis (RA) patients and to investigate factors associated with high adherence. METHODS RA patients, undergoing treatment with ≥1 self-administered conventional synthetic disease-modifying anti-rheumatic drug (csDMARD) or biological DMARD (bDMARD), were enrolled. The cross-cultural adaptation and validation of I-CQR5 followed standardised guidelines. I-CQR5 was completed by patients on one occasion. Data were subjected to factor analysis and Partial Credit model Parametrisation (PCM) to assess construct validity of I-CQR5. Analysis of factors associated with high adherence included demographic, social, clinical an...
Does dopamine code for uncertainty (Fiorillo, Tobler & Schultz, 2003; 2005) or is the sustained a... more Does dopamine code for uncertainty (Fiorillo, Tobler & Schultz, 2003; 2005) or is the sustained activation recorded from dopamine neurons a result of Temporal Difference (TD) backpropagating errors (Niv, Duff & Dayan, 2005)? An answer to this question could result in a better understanding of the nature of dopamine signaling, with implications for cognitive disorders, like Schizophrenia. A computer simulation of uncertainty incorporating TD Learning successfully modelled a Reinforcement Learning paradigm and the detailed effects demonstrated in single dopamine neuron recordings by Fiorillo et al. This alternate model provides further evidence that the sustained increase seen in dopamine firing, during uncertainty, is a result of averaging firing from dopamine neurons across trials, and is not normally found within individual trials, supporting the claims of Niv and colleagues.
A review of the current dopamine theories of schizophrenia reveals a likely imbalance between cor... more A review of the current dopamine theories of schizophrenia reveals a likely imbalance between cortical and subcortical microcircuits due to an insufficient inhibitory brake, leading to a disruption of the dopamine system and the classic positive psychotic symptoms, negative symptoms and cognitive deficits associated with the disorder. Recent computational models have modelled the role of dopamine as a reward prediction error, using Temporal Difference and have successfully shown how these symptoms could arise from a disturbance to the dopamine system. We review these models in the light of dopamine theories of schizophrenia and highlight some of the major points that should be addressed by future computational models.
Lecture Notes in Computer Science
The work outlined in this paper explores the influence of prior knowledge and related experience ... more The work outlined in this paper explores the influence of prior knowledge and related experience (held in the form of weights) on the generalisation performance of connectionist models. Networks were trained on simple classification and associated tasks. Results regarding the transfer of related experience between networks trained using backpropagation and recurrent networks performing sequence production, are reported. In terms of prior knowledge, results demonstrate that experienced networks produced their most pronounced generalisation performance advantage over naïve networks when a specific point of difficulty during learning was identified and an incremental training strategy applied at this point. Interestingly, the second set of results showed that knowledge learnt about in one task could be used to facilitate learning of a different but related task. However, in the third experiment, when the network architecture was changed, prior knowledge did not provide any advantage and indeed when learning was expanded, even found to deteriorated.
Rheumatology, 2010
factors. It is now becoming clear that, despite the apparent clinical and phenotypic differences ... more factors. It is now becoming clear that, despite the apparent clinical and phenotypic differences of the autoimmune diseases, they share a number of genetic risk factors. Of note there has been overlap between type 1 diabetes (T1D) and celiac disease (CD). Many of these loci are also susceptibility loci for rheumatoid arthritis (RA). There is already strong evidence suggesting that JIA shares many susceptibility loci with other autoimmune diseases, such as rheumatoid arthritis (RA), type 1 diabetes and multiple sclerosis (MS). Therefore the aim of this study was to test SNPs robustly associated with T1D or CD in a large cohort of JIA cases and controls to investigate the overlap between these diseases. Methods: Sixteen SNPs that showed robust association (P < 5 x 10-7) with T1D and CD and had not been investigated previously in JIA were genotyped in JIA cases (n ¼ 1054) and healthy controls (n ¼ 3129). Genotype and allele frequencies were compared between cases with JIA and controls using the Cochrane-Armitage trend test implemented in PLINK and allelic odds ratios (ORs) and their 95% confidence intervals (CIs) calculated. Results: One SNP in the Lim domain containing preferred translocation partner in lipoma (LPP) gene showed significant association with JIA (ptrend ¼ 0.002 OR 1.18 95% CI 1.06-1.30). A second SNP, rs653178, in ATXN2 showed a trend towards association with JIA however this was not significant after correction for multiple testing (ptrend ¼ 0.02 OR 1.13 95% CI 1.02-1.25). SNPs in this region, have previously shown evidence for association with JIA in a US cohort. A SNP, rs17810546, in IL12A showed a significant allele frequency difference (P ¼ 0.03) between the subtypes and this was driven by a strong association with enthesitis related arthritis (ERA) subtype (ptrend ¼ 0.005 OR 1.88 95% CI 1.2-2.94). Conclusions: We present evidence for a novel JIA susceptibility locus, LPP. LPP has a number of known functions including cell migration and adhesion, has transcriptional activation capacity and has recently been identified as a substrate of protein-tyrosine phosphatase 1B. We present confirmatory evidence for association of the SH2B3/ATXN2/ c12orf30 region with JIA. In addition we identify a subtype specific association of IL12A with ERA. All findings will require validation in independent JIA data sets. Acknowledgements: Childhood arthritis prospective study (CAPS), UKRAG consortium and BSPAR study group. Disclosure statement: All authors have declared no conflicts of interest.
Running Title: pragmatic use of language in pre-morbid adolescents Abstract At eleven years of ag... more Running Title: pragmatic use of language in pre-morbid adolescents Abstract At eleven years of age all children in a UK national birth cohort wrote short stories about the life they expected to be leading at age 25. Using a data linkage exercise, we identified those who later developed schizophrenia , affective psychosis , or other non-psychotic psychiatric disorders in later life based on the PSE CATEGO diagnostic system. The majority of these had completed the written essays. Controls from the reference population were selected , matched for gender, IQ and social and economic status. The essays were scored using well established methods for assessing pragmatic use of language, namely narrative coherence and linguistic cohesion. We hypothesised that children pre-morbid for schizophrenia (Pre-Scz) would obtain low scores on all these measures. However this general hypothesis was largely disproved by the data, although some unpredicted gender effects were found. It is concluded that ...
factors. It is now becoming clear that, despite the apparent clinical and phenotypic differences ... more factors. It is now becoming clear that, despite the apparent clinical and phenotypic differences of the autoimmune diseases, they share a number of genetic risk factors. Of note there has been overlap between type 1 diabetes (T1D) and celiac disease (CD). Many of these loci are also susceptibility loci for rheumatoid arthritis (RA). There is already strong evidence suggesting that JIA shares many susceptibility loci with other autoimmune diseases, such as rheumatoid arthritis (RA), type 1 diabetes and multiple sclerosis (MS). Therefore the aim of this study was to test SNPs robustly associated with T1D or CD in a large cohort of JIA cases and controls to investigate the overlap between these diseases. Methods: Sixteen SNPs that showed robust association (P < 5 x 10-7) with T1D and CD and had not been investigated previously in JIA were genotyped in JIA cases (n ¼ 1054) and healthy controls (n ¼ 3129). Genotype and allele frequencies were compared between cases with JIA and controls using the Cochrane-Armitage trend test implemented in PLINK and allelic odds ratios (ORs) and their 95% confidence intervals (CIs) calculated. Results: One SNP in the Lim domain containing preferred translocation partner in lipoma (LPP) gene showed significant association with JIA (ptrend ¼ 0.002 OR 1.18 95% CI 1.06-1.30). A second SNP, rs653178, in ATXN2 showed a trend towards association with JIA however this was not significant after correction for multiple testing (ptrend ¼ 0.02 OR 1.13 95% CI 1.02-1.25). SNPs in this region, have previously shown evidence for association with JIA in a US cohort. A SNP, rs17810546, in IL12A showed a significant allele frequency difference (P ¼ 0.03) between the subtypes and this was driven by a strong association with enthesitis related arthritis (ERA) subtype (ptrend ¼ 0.005 OR 1.88 95% CI 1.2-2.94). Conclusions: We present evidence for a novel JIA susceptibility locus, LPP. LPP has a number of known functions including cell migration and adhesion, has transcriptional activation capacity and has recently been identified as a substrate of protein-tyrosine phosphatase 1B. We present confirmatory evidence for association of the SH2B3/ATXN2/ c12orf30 region with JIA. In addition we identify a subtype specific association of IL12A with ERA. All findings will require validation in independent JIA data sets. Acknowledgements: Childhood arthritis prospective study (CAPS), UKRAG consortium and BSPAR study group. Disclosure statement: All authors have declared no conflicts of interest.
A Model of Dopamine and Uncertainty Using Temporal Difference Angela J. Thurnham* (a.j.thurnham@h... more A Model of Dopamine and Uncertainty Using Temporal Difference Angela J. Thurnham* (a.j.thurnham@herts.ac.uk), D. John Done** (d.j.done@herts.ac.uk), Neil Davey* (n.davey@herts.ac.uk), Ray J. Frank* (r.j.frank@herts.ac.uk) School of Computer Science,* School of Psychology, **University of Hertfordshire, College Lane, Hatfield, Hertfordshire. AL10 9AB United Kingdom from their electrophysiological characteristics, during a delay paradigm of classical conditioning to receive a fixed juice reward, while manipulating the probability of receipt of the reward. Two related but distinct parameters of reward were identified from the activation produced, after learning had taken place: (i) A phasic burst of activity, or reward prediction error, at the time of the expected reward, whose magnitude increased as probability decreased; and (ii) a new slower, sustained activity, above baseline, related to motivationally relevant stimuli, which developed with increasing levels of uncertainty, and var...
A Connectionist Model of the Role of Dopamine in Incentive Salience and Temporal Difference learn... more A Connectionist Model of the Role of Dopamine in Incentive Salience and Temporal Difference learning Angela J. Thurnham* (a.j.thurnham@herts.ac.uk), D. John Done** (d.j.done@herts.ac.uk), Neil Davey* (n.davey@herts.ac.uk), Ray J. Frank* (r.j.frank@herts.ac.uk) School of Computer Science,* School of Psychology, **University of Hertfordshire, College Lane, Hatfield, Hertfordshire. AL10 9AB England Dopamine as a Prediction Error (PE) Signal in Reinforcement Learning Dopamine is a neurotransmitter and disruption to this system has long been associated with the neuropsychiatric disorder, schizophrenia. Current theories of the effects of dopamine on behaviour focus on the role of dopamine in Reinforcement Learning, where organisms learn to organise their behaviour under the influence of goals, and expected future reward is believed to drive action selection. Reward Prediction Hypothesis Schultz and colleagues have demonstrated that dopamine neurons in the midbrain regions are particularly...
Research data supporting "Interpretation of published meta-analytical studies affected by implementation errors in the GingerALE software
An interpretative phenomenological analysis of service users’ experiences in a psychosocial addictions intervention
Psychology and Psychotherapy: Theory, Research and Practice
Archives of Neuropsychiatry
Introduction: Previous studies showed that over the course of learning many neurons in the medial... more Introduction: Previous studies showed that over the course of learning many neurons in the medial prefrontal cortex adapt their firing rate towards the options with highest predicted value reward but it was showed that during later learning trials the brain switches to a more automatic processing mode governed by the basal ganglia. Based on this evidence, we hypothesized that during the early learning trials the predicted values of chosen options will be coded by a goal directed system in the medial frontal cortex but during the late trials the predicted values will be coded by the habitual learning system in the dorsal striatum. Methods: In this study, using a 3 Tesla functional magnetic resonance imaging scanner (fMRI), blood oxygen level dependent signal (BOLD) data was collected whilst participants (N=12) performed a reinforcement learning task. The task consisted of instrumental conditioning trials wherein each trial a participant choose one of the two available options in order to win or avoid losing money. In addition to that, depending on the experimental condition, participants received either monetary reward (gain money), monetary penalty (lose money) or neural outcome. Results: Using model-based analysis for functional magnetic resonance imaging (fMRI) event related designs; region of interest (ROI) analysis was performed to nucleus accumbens, medial frontal cortex, caudate nucleus, putamen and globus pallidus internal and external segments. In order to compare the difference in brain activity for early (goal directed) versus late learning (habitual, automatic) trials, separate ROI analyses were performed for each anatomical sub-region. For the reward condition, we found significant activity in the medial frontal cortex (p<0.05) only for early learning trials but activity is shifted to bilateral putamen (p<0.05) during later trials. However, for the loss condition no significant activity was found for early trials except globus pallidus internal segment showed a significant activity (p<0.05) for later trials. Conclusion: We found that during reinforcement learning activation in the brain shifted from the medial frontal regions to dorsal regions of the striatum. These findings suggest that there are two separable (early goal directed and late habitual) learning systems in the brain.
Brain Sciences
Reinforcement learning studies in rodents and primates demonstrate that goal-directed and habitua... more Reinforcement learning studies in rodents and primates demonstrate that goal-directed and habitual choice behaviors are mediated through different fronto-striatal systems, but the evidence is less clear in humans. In this study, functional magnetic resonance imaging (fMRI) data were collected whilst participants (n = 20) performed a conditional associative learning task in which blocks of novel conditional stimuli (CS) required a deliberate choice, and blocks of familiar CS required an intuitive choice. Using standard subtraction analysis for fMRI event-related designs, activation shifted from the dorso-fronto-parietal network, which involves dorsolateral prefrontal cortex (DLPFC) for deliberate choice of novel CS, to ventro-medial frontal (VMPFC) and anterior cingulate cortex for intuitive choice of familiar CS. Supporting this finding, psycho-physiological interaction (PPI) analysis, using the peak active areas within the PFC for novel and familiar CS as seed regions, showed funct...
Neurological Sciences and Neurophysiology
Functional imaging studies offer alternative explanations for the neural correlates of monetary g... more Functional imaging studies offer alternative explanations for the neural correlates of monetary gain and loss related brain activity, and their opponents, omission of gains and losses. One possible explanation based on the psychology of opponent process theory suggests that successful avoidance of an aversive outcome is itself rewarding, and hence activates brain regions involved in reward processing. In order to test this hypothesis, we compared brain activation for successful avoidance of losses and receipt of monetary gains. Additionally, the brain regions involved in processing of frustrative neutral outcomes and actual losses were compared in order to test whether these two representations are coded in common or distinct brain regions. Methods: Using a 3 Tesla functional magnetic resonance imaging machine, fifteen healthy volunteers between the ages 22 to 28 were scanned for blood oxygen level dependent signal changes while they were performing a probabilistic learning task, wherein each trial a participant chose one of the two available options in order to win or avoid losing money. Results: The results confirmed, previous findings showing that medial frontal cortex and ventral striatum show significant activation (p<0.001) not only for monetary gains but also for successful avoidance of losses. A similar activation pattern was also observed for monetary losses and avoidance of gains in the medial frontal cortex, and posterior cingulate cortex, however, there was increased activation in amygdala specific to monetary losses (p<0.001). Further, subtraction analysis showed that regardless of the type of loss (i.e., frustrative neutral outcomes) posterior insula showed increased activation. Conclusion: This study provides evidence for a significant overlap not only between gains and losses, but also between their opponents. The results suggested that the overlapping activity pattern in the medial frontal cortex could be explained by a more abstract function of medial frontal cortex, such as outcome evaluation or performance monitoring, which possibly does not differentiate between winning and losing monetary outcomes.