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

John Mcgonigle,Anna Murphy,John Suckling,Jonathan Nash,Csaba Orban,Liam Nestor,Richard M Elliott ,David Nutt ,Bill Deakin ,Karen D Ersche ,Eleanor Taylor ,Rexford D Newbould ,Dana Smith ,Laurence Reed ,Trevor W Robbins ,Anne Lingford-Hughes ,Adam D Waldman ,Louise M Paterson ,Remy Flechais ,Iccam Platform

doi:10.1177/0269881116668592

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.

Highlights

Addiction is a major global health problem, with illicit drug and alcohol use disorders contributing to approximately 20% of the burden from mental health disorders (Whiteford et al, 2013)
For the monetary incentive delay task, we identified an initial total of 487 studies from searches on PubMed, and 170 from the BrainMap database, with 156 of the latter being duplicates of the former
Four clusters were found after carrying out the activation likelihood estimation (ALE) analysis, the two largest of these being focused on the anterior region of the left and right putamen and overlapping with portions of caudate, nucleus accumbens and globus pallidus

Summary

Introduction

Addiction is a major global health problem, with illicit drug and alcohol use disorders contributing to approximately 20% of the burden from mental health disorders (Whiteford et al, 2013). Of concern is the lack of effective interventions for these disorders, whilst the prevalence of alcohol, opioid and cocaine addiction is increasing (Lingford-Hughes et al, 2012; Whiteford et al, 2013). Studying the neurobiology of addiction can be challenging due to its common relapsing–remitting clinical course. A collaboration between Imperial College London, the University of Cambridge and the University of Manchester (ICCAM; http://www.bbmh.manchester.ac.uk/ICCAM/) was formed under a Medical Research Council (MRC) addiction initiative to maximize the existing magnetic resonance imaging (MRI) and clinical infrastructure and expertise available in the UK. Establishment of a platform is necessary to provide sufficient throughput to rapidly evaluate potential pharmacological

Objectives

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Discussion

Conclusion