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Biomarkers, designs, and interpretations of resting-state fMRI in translational pharmacological research: A review of state-of-the-art, challenges and opportunities for studying brain chemistry

Khalili-Mahani, Najmeh, Rombouts, Serge, Osch, Matthias, Dugg, Eugene, Carbonell, Felix, Nickerson, Lisa, Becerra, Lino, Dahan, Albert, Evans, Alan, Soucy, Jean-Paul, Wise, Richard, Zijdenbos, Alex and van Gerven, Joop 2017. Biomarkers, designs, and interpretations of resting-state fMRI in translational pharmacological research: A review of state-of-the-art, challenges and opportunities for studying brain chemistry. Human Brain Mapping 38 (4) , pp. 2276-2325. 10.1002/hbm.23516

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Abstract

A decade of research and development in resting-state functional MRI (RSfMRI) has opened new translational and clinical research frontiers. This review aims to bridge between technical and clinical researchers who seek reliable neuroimaging biomarkers for studying drug interactions with the brain. About 85 pharma-RSfMRI studies using BOLD signal (75% of all) or arterial spin labeling (ASL) were surveyed to investigate the acute effects of psychoactive drugs. Experimental designs and objectives include drug fingerprinting dose-response evaluation, biomarker validation and calibration, and translational studies. Common biomarkers in these studies include functional connectivity, graph metrics, cerebral blood flow and the amplitude and spectrum of BOLD fluctuations. Overall, RSfMRI-derived biomarkers seem to be sensitive to spatiotemporal dynamics of drug interactions with the brain. However, drugs cause both central and peripheral effects, thus exacerbate difficulties related to biological confounds, structured noise from motion and physiological confounds, as well as modeling and inference testing. Currently, these issues are not well explored, and heterogeneities in experimental design, data acquisition and preprocessing make comparative or meta-analysis of existing reports impossible. A unifying collaborative framework for data-sharing and data-mining is thus necessary for investigating the commonalities and differences in biomarker sensitivity and specificity, and establishing guidelines. Multimodal datasets including sham-placebo or active control sessions and repeated measurements of various psychometric, physiological, metabolic and neuroimaging phenotypes are essential for pharmacokinetic/pharmacodynamic modeling and interpretation of the findings. We provide a list of basic minimum and advanced options that can be considered in design and analyses of future pharma-RSfMRI studies. Hum Brain Mapp 38:2276-2325, 2017.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Uncontrolled Keywords: PK/PD modeling; arterial spin labeling; biomarkers; brain chemistry; drug; functional connectivity; pharma-fMRI; pharmacological neuroimaging; resting state fMRI; translational research
Publisher: Wiley-Blackwell
ISSN: 1065-9471
Date of First Compliant Deposit: 13 March 2017
Date of Acceptance: 4 January 2017
Last Modified: 04 Jun 2017 09:44
URI: http://orca.cf.ac.uk/id/eprint/98925

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