Variability in spatial normalization of pediatric and adult brain images Marco R. Hoeksma a, * , J. Leon Kenemans b , Chantal Kemner c , Herman van Engeland c a Department of Psychopharmacology, Faculty of Pharmaceutical Sciences, Utrecht University, Sorbonnelaan 16, 3584CA Utrecht, The Netherlands b Department of Psychonomics, Faculty of Social Sciences, Utrecht University, Utrecht, The Netherlands c Department of Child- and Adolescent Psychiatry, Utrecht University Medical Center, Utrecht, The Netherlands Accepted 21 December 2004 Abstract Objective: Normalization of brain images is a necessity for group comparisons of source analyses based on realistic head models. In this paper we compared the outcome of a linear registration method for brain images of psychiatric and control groups of different ages in order to assess the relative adequacy of normalization in such diverse groups. Methods: Magnetic Resonance images (MRI) of the brains of pediatric and adolescent subjects (mean ages 19 and 10.5 years) with a pervasive developmental disorder (PDD) and their healthy controls were included. A simple voxel-wise test of the group variances in image intensities was performed to evaluate regional differences in registration quality. Dipole analysis of visual P1 was performed to establish whether source locations were comparable across groups. Results: Significant differences between pediatric groups were found in white matter and thalamic regions of the brain. For all other group- wise comparisons, differences were confined to skull and neck regions. Dipole locations were found to be more anteriorly located in the adolescent groups. Conclusions: The normalization procedure used in this paper is based on a brain template of normal adult brains from a restricted age group, and the results show that the use of this method in pediatric groups is less adequate. The method seems suitable for use in psychiatric groups. Also, the generators of visual P1 in PDD patients were found to be comparable to controls. Significance: The results suggest that this existing normalization method can be used in diverse populations, but is less suitable for pediatric images. q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Head model; Magnetic resonance imaging; Source localization; Spatial normalization; Pervasive developmental disorder; P1 1. Introduction In order to increase the accuracy of head models for electrical and magnetic source analyses, structural brain images have entered the field of electrophysiology (Fuchs et al., 2001; Wagner, 1998). Traditionally, spherical models were used to model the head (Scherg, 1990). The assumed spherical dimensions in these models were similar for all subjects and a direct link to the anatomy was missing. Structural images of the head have the advantage of enabling the researcher to construct a head model that is tailor made for each subject under study, thus improving localization accuracy and opening the way for inferences about the brain structures involved in the modeled electrophysiological phenomena. Although individual head models improve the quality of single-subject localizations, they introduce a new source of variance in group-wise comparisons of localiz- ation results. In order to facilitate group comparisons and the generalization of findings, individual variability in brain images has to be minimized. This minimization, or spatial normalization, is achieved by transforming the individual image to a common template that is aligned in standardized stereotaxic space. However, it may be that the use of such a common standardized template results in errors that differ in size or nature across age- or patient groups. The present work addresses potential differences in error patterns between typical age and clinical groups. Clinical Neurophysiology 116 (2005) 1188–1194 www.elsevier.com/locate/clinph 1388-2457/$30.00 q 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2004.12.021 * Corresponding author. Tel.: C31 30 2533845; fax: C31 30 2537387. E-mail address: m.r.hoeksma@pharm.uu.nl (M.R. Hoeksma).