title: Challenges in the reproducibility of clinical studies with resting state fMRI: An example in early Parkinson's disease.
abstract: Resting state fMRI (rfMRI) is gaining in popularity, being easy to acquire and with promising clinical applications. However, rfMRI studies, especially those involving clinical groups, still lack reproducibility, largely due to the different analysis settings. This is particularly important for the development of imaging biomarkers. The aim of this work was to evaluate the reproducibility of our recent study regarding the functional connectivity of the basal ganglia network in early Parkinson's disease (PD) (Szewczyk-Krolikowski et al., 2014). In particular, we systematically analysed the influence of two rfMRI analysis steps on the results: the individual cleaning (artefact removal) of fMRI data and the choice of the set of independent components (template) used for dual regression. Our experience suggests that the use of a cleaning approach based on single-subject independent component analysis, which removes non neural-related sources of inter-individual variability, can help to increase the reproducibility of clinical findings. A template generated using an independent set of healthy controls is recommended for studies where the aim is to detect differences from a "healthy" brain, rather than an "average" template, derived from an equal number of patients and controls. While, exploratory analyses (e.g. testing multiple resting state networks) should be used to formulate new hypotheses, careful validation is necessary before promising findings can be translated into useful biomarkers.
authors.affiliation: Centre for the functional MRI of the Brain (FMRIB), University of Oxford, Oxford, UK.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Griffanti
authors.affiliation: Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Michal
authors.initials: M
authors.lastname: Rolinski
authors.affiliation: Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Konrad
authors.initials: K
authors.lastname: Szewczyk-Krolikowski
authors.affiliation: Centre for the functional MRI of the Brain (FMRIB), University of Oxford, Oxford, UK.
authors.forename: Ricarda A
authors.initials: RA
authors.lastname: Menke
authors.affiliation: Centre for the functional MRI of the Brain (FMRIB), University of Oxford, Oxford, UK; Department of Psychiatry, University of Oxford, Oxford, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Filippini
authors.affiliation: Centre for the functional MRI of the Brain (FMRIB), University of Oxford, Oxford, UK.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Zamboni
authors.affiliation: Centre for the functional MRI of the Brain (FMRIB), University of Oxford, Oxford, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkinson
authors.affiliation: Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, UK; Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
authors.forename: Michele T M
authors.initials: MTM
authors.lastname: Hu
authors.affiliation: Centre for the functional MRI of the Brain (FMRIB), University of Oxford, Oxford, UK; Oxford Parkinson's Disease Centre (OPDC), University of Oxford, Oxford, UK; Department of Psychiatry, University of Oxford, Oxford, UK. Electronic address: clare.mackay@psych.ox.ac.uk.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Mackay
mesh_terms: D000368:Aged; D016477:Artifacts; D001479:Basal Ganglia / Q000473:pathology; D001931:Brain Mapping; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007206:Individuality; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000473:pathology*; D012016:Reference Values; D012044:Regression Analysis; D015203:Reproducibility of Results; D012146:Rest; D059629:Signal-To-Noise Ratio
keywords: Artefact removal; Basal ganglia network; Dual regression; Functional connectivity; Parkinson's disease; Resting state functional magnetic resonance imaging (rfMRI)