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John O'Doherty

Shinsuke Suzuki, Logan Cross, John P O'Doherty
The valuation of food is a fundamental component of our decision-making. Yet little is known about how value signals for food and other rewards are constructed by the brain. Using a food-based decision task in human participants, we found that subjective values can be predicted from beliefs about constituent nutritive attributes of food: protein, fat, carbohydrates and vitamin content. Multivariate analyses of functional MRI data demonstrated that, while food value is represented in patterns of neural activity in both medial and lateral parts of the orbitofrontal cortex (OFC), only the lateral OFC represents the elemental nutritive attributes...
December 2017: Nature Neuroscience
Ryan A West, Oran G O'Doherty, Trevor Askwith, John Atack, Paul Beswick, Jamie Laverick, Michael Paradowski, Lewis E Pennicott, Srinivasa P S Rao, Gareth Williams, Simon E Ward
African trypanosomiasis is a parasitic disease affecting 5000 humans and millions of livestock animals in sub-Saharan Africa every year. Current treatments are limited, difficult to administer and often toxic causing long term injury or death in many patients. Trypanosome alternative oxidase is a parasite specific enzyme whose inhibition by the natural product ascofuranone (AF) has been shown to be curative in murine models. Until now synthetic methods to AF analogues have been limited, this has restricted both understanding of the key structural features required for binding and also how this chemotype could be developed to an effective therapeutic agent...
December 1, 2017: European Journal of Medicinal Chemistry
Sven Collette, Wolfgang M Pauli, Peter Bossaerts, John O'Doherty
In inverse reinforcement learning an observer infers the reward distribution available for actions in the environment solely through observing the actions implemented by another agent. To address whether this computational process is implemented in the human brain, participants underwent fMRI while learning about slot machines yielding hidden preferred and non-preferred food outcomes with varying probabilities, through observing the repeated slot choices of agents with similar and dissimilar food preferences...
October 30, 2017: ELife
Jaron T Colas, Wolfgang M Pauli, Tobias Larsen, J Michael Tyszka, John P O'Doherty
Prediction-error signals consistent with formal models of "reinforcement learning" (RL) have repeatedly been found within dopaminergic nuclei of the midbrain and dopaminoceptive areas of the striatum. However, the precise form of the RL algorithms implemented in the human brain is not yet well determined. Here, we created a novel paradigm optimized to dissociate the subtypes of reward-prediction errors that function as the key computational signatures of two distinct classes of RL models-namely, "actor/critic" models and action-value-learning models (e...
October 2017: PLoS Computational Biology
Christopher A Hill, Shinsuke Suzuki, Rafael Polania, Marius Moisa, John P O'Doherty, Christian C Ruff
During competitive interactions, humans have to estimate the impact of their own actions on their opponent's strategy. Here we provide evidence that neural computations in the right temporoparietal junction (rTPJ) and interconnected structures are causally involved in this process. By combining inhibitory continuous theta-burst transcranial magnetic stimulation with model-based functional MRI, we show that disrupting neural excitability in the rTPJ reduces behavioral and neural indices of mentalizing-related computations, as well as functional connectivity of the rTPJ with ventral and dorsal parts of the medial prefrontal cortex...
August 2017: Nature Neuroscience
Justin Reber, Justin S Feinstein, John P O'Doherty, Mimi Liljeholm, Ralph Adolphs, Daniel Tranel
June 1, 2017: Brain: a Journal of Neurology
John P O'Doherty, Jeffrey Cockburn, Wolfgang M Pauli
In this review, we summarize findings supporting the existence of multiple behavioral strategies for controlling reward-related behavior, including a dichotomy between the goal-directed or model-based system and the habitual or model-free system in the domain of instrumental conditioning and a similar dichotomy in the realm of Pavlovian conditioning. We evaluate evidence from neuroscience supporting the existence of at least partly distinct neuronal substrates contributing to the key computations necessary for the function of these different control systems...
January 3, 2017: Annual Review of Psychology
Jean-Claude Dreher, Simon Dunne, Agnieszka Pazderska, Thomas Frodl, John J Nolan, John P O'Doherty
Although popular discussion of testosterone's influence on males often centers on aggression and antisocial behavior, contemporary theorists have proposed that it instead enhances behaviors involved in obtaining and maintaining a high social status. Two central distinguishing but untested predictions of this theory are that testosterone selectively increases status-relevant aggressive behaviors, such as responses to provocation, but that it also promotes nonaggressive behaviors, such as generosity toward others, when they are appropriate for increasing status...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
Olugbeminiyi Fadeyi, Mihir D Parikh, Ming Z Chen, Robert E Kyne, Alexandria P Taylor, Inish O'Doherty, Stephen E Kaiser, Sabrina Barbas, Sherry Niessen, Manli Shi, Scott L Weinrich, John C Kath, Lyn H Jones, Ralph P Robinson
Sulfonyl fluoride (SF)-based activity probes have become important tools in chemical biology. Herein, exploiting the relative chemical stability of SF to carry out a number of unprecedented SF-sparing functional group manipulations, we report the chemoselective synthesis of a toolbox of highly functionalized aryl SF monomers that we used to quickly prepare SF chemical biology probes. In addition to SF, the monomers bear an embedded click handle (a terminal alkyne that can perform copper(I)-mediated azide-alkyne cycloaddition)...
October 17, 2016: Chembiochem: a European Journal of Chemical Biology
Aoife Hayes, Sarah Duffy, Michael O'Grady, Jette Jakobsen, Karen Galvin, Joanna Teahan-Dillon, Joseph Kerry, Alan Kelly, John O'Doherty, Siobhan Higgins, Kelly M Seamans, Kevin D Cashman
BACKGROUND: Despite numerous animal studies that have illustrated the impact of additional vitamin D in the diet of hens on the resulting egg vitamin D content, the effect of the consumption of such eggs on vitamin D status of healthy individuals has not, to our knowledge, been tested. OBJECTIVE: We performed a randomized controlled trial (RCT) to investigate the effect of the consumption of vitamin D-enhanced eggs (produced by feeding hens at the maximum concentration of vitamin D3 or serum 25-hydroxyvitamin D [25(OH)D3] lawfully allowed in feed) on winter serum 25(OH)D in healthy adults...
September 2016: American Journal of Clinical Nutrition
B Bahar, J V O'Doherty, S Vigors, T Sweeney
The technique of challenging postmortem tissue explants with inflammation inducer such as lipopolysaccharide (LPS) followed by gene expression analysis is used widely for evaluating the immune-suppressing effect of bioactives. Using porcine colonic tissue as an ex-vivo model of mammalian intestinal gut, this study evaluated the effect of incubation time on the integrity of gene transcripts and activation of inflammatory immune gene cascade by LPS treatment. Post-slaughter colon was removed surgically and explants were incubated for 0, 3, 6 and 12 h and the abundance of mRNA transcripts of a panel of 92 immune genes were evaluated using quantitative polymerase chain reaction (qPCR) arrays...
November 2016: Clinical and Experimental Immunology
Karl Friston, Thomas FitzGerald, Francesco Rigoli, Philipp Schwartenbeck, John O Doherty, Giovanni Pezzulo
This paper offers an active inference account of choice behaviour and learning. It focuses on the distinction between goal-directed and habitual behaviour and how they contextualise each other. We show that habits emerge naturally (and autodidactically) from sequential policy optimisation when agents are equipped with state-action policies. In active inference, behaviour has explorative (epistemic) and exploitative (pragmatic) aspects that are sensitive to ambiguity and risk respectively, where epistemic (ambiguity-resolving) behaviour enables pragmatic (reward-seeking) behaviour and the subsequent emergence of habits...
September 2016: Neuroscience and Biobehavioral Reviews
Peter Johnson, Massimo Federico, Amy Kirkwood, Alexander Fosså, Leanne Berkahn, Angelo Carella, Francesco d'Amore, Gunilla Enblad, Antonella Franceschetto, Michael Fulham, Stefano Luminari, Michael O'Doherty, Pip Patrick, Thomas Roberts, Gamal Sidra, Lindsey Stevens, Paul Smith, Judith Trotman, Zaid Viney, John Radford, Sally Barrington
BACKGROUND: We tested interim positron-emission tomography-computed tomography (PET-CT) as a measure of early response to chemotherapy in order to guide treatment for patients with advanced Hodgkin's lymphoma. METHODS: Patients with newly diagnosed advanced classic Hodgkin's lymphoma underwent a baseline PET-CT scan, received two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy, and then underwent an interim PET-CT scan. Images were centrally reviewed with the use of a 5-point scale for PET findings...
June 23, 2016: New England Journal of Medicine
Wolfgang M Pauli, John P O'Doherty
No abstract text is available yet for this article.
June 1, 2016: Biological Psychiatry
Simon Dunne, Arun D'Souza, John P O'Doherty
A major open question is whether computational strategies thought to be used during experiential learning, specifically model-based and model-free reinforcement learning, also support observational learning. Furthermore, the question of how observational learning occurs when observers must learn about the value of options from observing outcomes in the absence of choice has not been addressed. In the present study we used a multi-armed bandit task that encouraged human participants to employ both experiential and observational learning while they underwent functional magnetic resonance imaging (fMRI)...
June 1, 2016: Journal of Neurophysiology
Shinsuke Suzuki, Emily L S Jensen, Peter Bossaerts, John P O'Doherty
Our attitude toward risk plays a crucial role in influencing our everyday decision-making. Despite its importance, little is known about how human risk-preference can be modulated by observing risky behavior in other agents at either the behavioral or the neural level. Using fMRI combined with computational modeling of behavioral data, we show that human risk-preference can be systematically altered by the act of observing and learning from others' risk-related decisions. The contagion is driven specifically by brain regions involved in the assessment of risk: the behavioral shift is implemented via a neural representation of risk in the caudate nucleus, whereas the representations of other decision-related variables such as expected value are not affected...
April 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
Áine M Egan, John V O'Doherty, Stafford Vigors, Torres Sweeney
The crustacean shells-derived polysaccharide chitosan has received much attention for its anti-obesity potential. Dietary supplementation of chitosan has been linked with reductions in feed intake, suggesting a potential link between chitosan and appetite control. Hence the objective of this experiment was to investigate the appetite suppressing potential of prawn shell derived chitosan in a pig model. Pigs (70 ± 0.90 kg, 125 days of age, SD 2.0) were fed either T1) basal diet or T2) basal diet plus 1000 ppm chitosan (n = 20 gilts per group) for 63 days...
2016: PloS One
Stafford Vigors, John V O'Doherty, Alan K Kelly, Cormac J O'Shea, Torres Sweeney
Feed efficiency is an important trait in pig production, with evidence to suggest that the efficiencies of a variety of biological systems contribute to variation in this trait. Little work has been conducted on the contribution of the intestinal innate immune response to divergence in feed efficiency. Hence, the objective of this study was to examine select bacterial populations and gene expression profiles of a range of targets relating to gut health and immunity in the intestine of pigs phenotypically divergent in feed efficiency in: a) the basal state; and (b) following an ex-vivo lipopolysaccharide (LPS) challenge of ileal and colonic tissue...
2016: PloS One
Sally F Barrington, Amy A Kirkwood, Antonella Franceschetto, Michael J Fulham, Thomas H Roberts, Helén Almquist, Eva Brun, Karin Hjorthaug, Zaid N Viney, Lucy C Pike, Massimo Federico, Stefano Luminari, John Radford, Judith Trotman, Alexander Fosså, Leanne Berkahn, Daniel Molin, Francesco D'Amore, Donald A Sinclair, Paul Smith, Michael J O'Doherty, Lindsey Stevens, Peter W Johnson
International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design...
March 24, 2016: Blood
Áine M Egan, Torres Sweeney, Maria Hayes, John V O'Doherty
The potential of natural products to prevent obesity have been investigated, with evidence to suggest that chitosan has anti-obesity effects. The current experiment investigated the anti-obesity potential of prawn shell derived chitosan on a range of variables relevant to obesity in a pig model. The two dietary treatment groups included in this 63 day study were: T1) basal diet and T2) basal diet plus 1000 ppm chitosan (n = 20 gilts per group (70 ± 0.90 kg). The parameter categories which were assessed included: performance, nutrient digestibility, serum leptin concentrations, nutrient transporter and digestive enzyme gene expression and gut microbial populations...
2015: PloS One
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