Intersubject Variability in Cortical Activations during a Complex Language Task Jinhu Xiong,* Shobini Rao, Paul Jerabek, Frank Zamarripa, Marty Woldorff, Jack Lancaster, and Peter T. Fox Research Imaging Center, The University of Texas Health Science Center, San Antonio, Texas; and *Department of Clinical Psychology, National Institute of Mental Health and Neurosciences, Bangalore, India Received May 23, 2000 Intersubject variability in the functional organization of the human brain has theoretical and practical impor- tance for basic and clinical neuroscience. In the present study, positron emission tomography (PET) and anatom- ical magnetic resonance imaging (MRI) were used to study the functional anatomy of language processes. In- tersubject variability in task-induced activations in six brain regions was assessed in 20 normal subjects (10 men and 10 women) for frequency of occurrence, loca- tion, intensity, and extent. A complex, but well-studied task (overt verb generation) was compared to a simple baseline (visual fixation) to induce activations in brain areas serving perceptual, motoric, and cognitive func- tions. The frequency of occurrence was high for all se- lected brain areas (80 –95%). The variability in response location in Talairach space, expressed as the standard deviation along each axis (x, y, z), ranged from 5.2 to 9.9 mm. This variability appears to be uniformly distributed across the brain, uninfluenced by regional differences in the complexity of gyral anatomy or mediated behavior. The variability in response location, expressed as the average Euclidean distances (averaged across subjects) about mean locations of activations, varied from 9.40 to 13.36 mm and had no significant differences by region (P > 0.05,  0.20). Intensity variability was also rela- tively small and homogenous across brain regions. In contrast, response extent was much more variable both across subjects and across brain regions (0.79 to 1.77, coefficient of variation). These findings are in good agreement with previous PET studies of intersubject variability and bode well for the possibility of using functional neuroimaging to study neural plasticity sub- sequent to congenital and acquired brain lesions. © 2000 Academic Press Key Words: PET; functional human brain mapping; functional anatomy; plasticity; verb generation. INTRODUCTION Individual variability in the functional organization of the human brain is an issue of relevance for basic neuroscience, for clinical neuroscience and clinical ap- plications of brain-mapping methods. The nature, pat- terns, and magnitude of intersubject variability in functional pacellation undoubtedly reflect important properties and features of brain development. To in- vestigate the mechanisms underlying the development of cortical functional organization, knowledge of the aver- age organizational pattern is insufficient. The nature and magnitude of normal variations must also be established. Despite the clear need for studies of variability in normal subjects, few such studies have been published. Functional mapping of the normal human brain is most readily performed with positron emission tomog- raphy (PET) and functional magnetic resonance imag- ing (fMRI). A large and rapidly growing literature re- ports the brain locations of a wide variety of cognitive, perceptual, motoric, and emotional processes. Of the PET studies to date, the majority have relied on inter- subject averaging and have reported grand-mean ef- fects. Rather than analyzing and reporting the func- tional organization for each individual, the individual mappings were averaged across subjects to increase the detection of very subtle (2–3%) neural activations (Fox et al., 1988; Friston et al., 1991). Intersubject averaging is done by spatially normalizing individual brains to a standard orientation, shape, and size, thereby placing all brain images in a common, three- dimensional, stereotactic coordinate space (Talairach and Tournoux, 1988; Fox et al., 1985b). Intersubject averaging has been instrumental in advancing our un- derstanding of the functional organization of the hu- man brain. The grand-averaging strategy, however, extracts only the collective effects of neural activations that are spatially coincident across subjects, providing no information about individual variability in func- tional organization of the human brain. Neuroimaging studies that report individual sub- jects—and, therefore, individual variability— do exist. Unfortunately, a substantial fraction of these studies has not reported their observations within a standard- ized coordinate space. This is particularly true for NeuroImage 12, 326 –339 (2000) doi:10.1006/nimg.2000.0621, available online at http://www.idealibrary.com on 326 1053-8119/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.