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Meta-Analysis
. 2017 Jan;31(1):3-16.
doi: 10.1177/0269881116668592. Epub 2016 Oct 4.

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description

John McGonigle  1 , Anna Murphy  2 , Louise M Paterson  1 , Laurence J Reed  1 , Liam Nestor  1   3 , Jonathan Nash  1 , Rebecca Elliott  2 , Karen D Ersche  3   4 , Remy Sa Flechais  1 , Rexford Newbould  5 , Csaba Orban  1 , Dana G Smith  4 , Eleanor M Taylor  2 , Adam D Waldman  6 , Trevor W Robbins  4   7 , Jf William Deakin  2 , David J Nutt  1 , Anne R Lingford-Hughes  1 , John Suckling  3   4   8 ; ICCAM Platform
Affiliations
Meta-Analysis

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description

John McGonigle et al. J Psychopharmacol. 2017 Jan.

Abstract

Objectives: We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction - reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants.

Experimental design: Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity. A coordinate-based activation likelihood estimation (ALE) meta-analysis was carried out for the reward and impulsivity tasks to help establish region of interest (ROI) placement. A group of healthy participants was recruited from across three centres (total n=43) to investigate inter-centre differences. Principle observations: The pattern of response observed for each of the three tasks was consistent with previous studies using similar paradigms. At the whole brain level, significant differences were not observed between centres for any task.

Conclusions: In developing this platform we successfully integrated neuroimaging data from three centres, adapted validated tasks and applied whole brain and ROI approaches to explore and demonstrate their consistency across centres.

Keywords: Brain; human; magnetic resonance imaging; substance-related disorders.

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Conflict of interest statement

Declaration of conflicting interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Liam J Nestor was a Senior Research Scientist employed by GlaxoSmithKline during this work.

Trevor W Robbins has research grants with Eli Lilly and Company and Lundbeck, has received royalties from Cambridge Cognition, has received editorial honoraria from Springer Verlag, Elsevier, Society for Neuroscience; has performed educational lectures for Merck Sharp & Dohme, and performs consultancy work for Cambridge Cognition, Eli Lilly and Company, Lundbeck, Teva Pharmaceutical Industries and Shire Pharmaceuticals.

JF William Deakin currently advises or carries out research funded by Autifony Therapeutics, Sunovion Pharmaceuticals, Lundbeck, AstraZeneca and Servier. All payment is to the The University of Manchester.

David J Nutt is an advisor to British National Formulary, Medical Research Council, General Medical Council, and Department of Health (UK), is President of the European Brain Council, past President of the British Neuroscience Association and European College of Neuropsychopharmacology, chair of the Independent Scientific Committee on Drugs (UK), is a member of the International Centre for Science in Drug Policy, advisor to Swedish government on drug, alcohol and tobacco research, editor of the Journal of Psychopharmacology, sits on advisory Boards at Lundbeck, Merck Sharp & Dohme, Nalpharm, Orexigen Therapeutics, Shire Pharmaceuticals, has received speaking honoraria (in addition to above) from Bristol-Myers Squibb/Otsuka, GlaxoSmithKline, Eli Lilly and Company, Janssen, Servier, is a member of the Lundbeck International Neuroscience Foundation, has received grants or clinical trial payments from P1vital, Medical Research Council, National Health Service, Lundbeck, has share options with P1vital, has been expert witness in a number of legal cases relating to psychotropic drugs and has edited/written 27 books – some purchased by pharmaceutical companies.

Anne R Lingford-Hughes has received honoraria from Lundbeck and research support from GlaxoSmithKline for a PhD studentship.

All other authors declared no conflict of interest.

Figures

Figure 1.
Figure 1.
Clusters found through the activation likelihood estimation (ALE) meta-analyses. ALE was performed for each task with a false discovery rate (FDR) of p<0.05 (corrected) and a minimum cluster volume of 0.6 ml.
Figure 2.
Figure 2.
The contrast of reward anticipation with neutral anticipation in the monetary incentive delay task in the combined group (n=43), controlling for centre, age and sex. Images were thresholded using clusters determined by Z>4.5 and a (corrected) cluster significance threshold of p<0.05. The slices shown were chosen such that all three intersect with the left side of the ROI used later in this work. The greyed out portion shows areas outside common coverage.
Figure 3.
Figure 3.
Unthresholded F maps exploring inter-centre differences. No significant imaging differences were found between centres at this whole brain (voxelwise) level.
Figure 4.
Figure 4.
The contrast of successful no-go with go (implicit baseline) in the go/no-go task in the combined group (n=43), controlling for centre, age and sex. Images were thresholded using clusters determined by Z>3.1 and a (corrected) cluster significance threshold of p<0.05. The slices shown were chosen such that all three intersect with the left side of the ROI used later in this work. The greyed out portion shows areas outside common coverage.
Figure 5.
Figure 5.
The contrast of aversive images with neutral images in the evocative images task in the combined group (n=43), controlling for centre, age, and sex. Images were thresholded using clusters determined by Z>3.1 and a (corrected) cluster significance threshold of p<0.05. The slices shown were chosen such that all three intersect with the left side of the ROI used later in this work. The greyed out portion shows areas outside common coverage.
See this image and copyright information in PMC

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