Group analysis and the subject factor in functional magnetic resonance imaging: Analysis of fifty right-handed healthy subjects in a semantic language task

• Published in: Human brain mapping Vol. 29; no. 4; pp. 461 - 477
• Main Authors: Seghier, Mohamed L., Lazeyras, François, Pegna, Alan J., Annoni, Jean-Marie, Khateb, Asaid
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.04.2008; Wiley-Liss
• Subjects: Adult; Biological and medical sciences; Brain - anatomy & histology; Brain - physiology; Brain Injuries - diagnosis; Brain Mapping - methods; clinical fMRI; Data Interpretation, Statistical; Dominance, Cerebral - physiology; Electrodiagnosis. Electric activity recording; False Negative Reactions; False Positive Reactions; Female; fixed and random effects; functional magnetic resonance imaging; gold standard map; group analysis; Humans; Image Processing, Computer-Assisted; inter-individual variability; Investigative techniques, diagnostic techniques (general aspects); Language; language areas; Language Tests; left hemisphere lateralisation; Magnetic Resonance Imaging - methods; Male; Medical sciences; Nerve Net - anatomy & histology; Nerve Net - physiology; Nervous system; Observer Variation; Radiodiagnosis. Nmr imagery. Nmr spectrometry; Sample Size; semantic categorisation; Semantics; Verbal Behavior - physiology; semantic categorisation; Sample size; Variability; clinical fMRI; Language; Semantics; Left hemisphere; gold standard map; Random effect; language areas; group analysis; Human; Cartography; Nervous system diseases; Factor analysis; Healthy subject; Radiodiagnosis; left hemisphere lateralisation; Functional analysis; Nuclear magnetic resonance imaging; Hand; fixed and random effects; inter-individual variability; functional magnetic resonance imaging; Functional imaging
• DOI: 10.1002/hbm.20410
• ISSN: 1065-9471

Before considering a given fMRI paradigm as a valid clinical tool, one should first assess the reliability of functional responses across subjects by establishing a normative database and defining a reference activation map that identifies major brain regions involved in the task at hand. However, the definition of such a reference map can be hindered by inter‐individual functional variability. In this study, we analysed functional data obtained from 50 healthy subjects during a semantic language task to assess the influence of the number of subjects on the reference map and to characterise inter‐individual functional variability. We first compared different group analysis approaches and showed that the extent of the activated network depends not only on the choice of the analysis approach but also on the statistical threshold used and the number of subjects included. This analysis suggested that, while the RFX analysis is suitable to detect confidently true positive activations, the other group approaches are useful for exploratory investigations in small samples. The application of quantitative measures at the voxel and regional levels suggested that while ∼15–20 subjects were sufficient to reveal reliable and robust left hemisphere activations, >30 subjects were necessary for revealing more variable and weak right hemisphere ones. Finally, to visualise inter‐individual variability, we combined two similarity indices that assess the percentages of true positive and false negative voxels in individual activation patterns relative to the group map. We suggest that these measures can be used for the estimation of the degree of ‘normality’ of functional responses in brain‐damaged patients, where this question is often raised, and recommend the use of different quantifications to appreciate accurately the inter‐individual functional variability that can be incorporated in group maps. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc.