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The role of machine learning in neuroimaging for drug discovery and development

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Abstract

Neuroimaging has been identified as a potentially powerful probe for the in vivo study of drug effects on the brain with utility across several phases of drug development spanning preclinical and clinical investigations. Specifically, neuroimaging can provide insight into drug penetration and distribution, target engagement, pharmacodynamics, mechanistic action and potential indicators of clinical efficacy. In this review, we focus on machine learning approaches for neuroimaging which enable us to make predictions at the individual level based on the distributed effects across the whole brain. Crucially, these approaches can be trained on data from one study and applied to an independent study and, unlike group-level statistics, can be readily use to assess the generalisability to unseen data. In this review, we present examples and suggestions for how machine learning could help answer fundamental questions spanning the drug discovery pipeline: (1) Who should I recruit for this study? (2) What should I measure and when should I measure it? (3) How does the pharmacological agent behave using an experimental medicine model?, and (4) How does a compound differ from and/or resemble existing compounds? Specifically, we present studies from the literature and we suggest areas for the focus of future development. Further refinement and tailoring of machine learning techniques may help realise their tremendous potential for drug discovery and drug validation.

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Acknowledgements

OMD gratefully acknowledges support from the EPSRC grant EP/L000296/1. OMD, MAM and MJB gratefully acknowledge support from the Innovative Medicines Initiative Joint Undertaking under Grant Agreement No 115008 (NEWMEDS). The Innovative Medicines Initiative Joint Undertaking is a public-private partnership between the European Union and the European Federation of Pharmaceutical Industries and Associations.

Conflict of interest

Over the past 5 years, Mitul A. Mehta has received research funding from Eli Lilly, Roche and Takeda; has acted as a consultant for Cambridge Cognition and Lundbeck and received fees from Shire for contributions towards education. All others declare no conflicts of interest.

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  1. Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, De Crespigny Park, London, SE5 8AF, UK

    Orla M. Doyle, Mitul A. Mehta & Michael J. Brammer

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  1. Orla M. Doyle
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  2. Mitul A. Mehta
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Correspondence to Orla M. Doyle.

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Doyle, O.M., Mehta, M.A. & Brammer, M.J. The role of machine learning in neuroimaging for drug discovery and development. Psychopharmacology 232, 4179–4189 (2015). https://doi.org/10.1007/s00213-015-3968-0

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