Language dominance determined by whole brain functional MRI in patients with brain lesions R.R. Benson, MD; D.B. FitzGerald, BSEE, MBA; L.L. LeSueur, PhD; D.N. Kennedy, PhD; K.K. Kwong, PhD; B.R. Buchbinder, MD; T.L. Davis, PhD; R.M. Weisskoff, PhD; T.M. Talavage, PhD; W.J. Logan, MD; G.R. Cosgrove, MD, FRCS(C); J.W. Belliveau, PhD; and B.R. Rosen, MD, PhD Article abstract—Background: Functional MRI (fMRI) is of potential value in determining hemisphere dominance for language in epileptic patients. Objective: To develop and validate an fMRI-based method of determining language domi- nance for patients with a wide range of potentially operable brain lesions in addition to epilepsy. Methods: Initially, a within-subjects design was used with 19 healthy volunteers (11 strongly right-handed, 8 left-handed) to determine the relative lateralizing usefulness of three different language tasks in fMRI. An automated, hemispheric analysis of laterality was used to analyze whole brain fMRI data sets. To evaluate the clinical usefulness of this method, we compared fMRI-determined laterality with laterality determined by Wada testing or electrocortical stimulation mapping, or both, in 23 consecutive patients undergoing presurgical evaluation of language dominance. Results: Only the verb generation task was reliably lateralizing. fMRI, using the verb generation task and an automated hemispheric analysis method, was concordant with invasive measures in 22 of 23 patients (12 Wada, 11 cortical stimulation). For the single patient who was discordant, in whom a tumor involved one-third of the left hemisphere, fMRI became concordant when the tumor and its reflection in the right hemisphere were excluded from laterality analysis. No significant negative correlation was obtained between lesion size and strength of laterality for the patients with lesions involving the dominant hemisphere. Conclusion: This fMRI method shows potential for evaluating language dominance in patients with a variety of brain lesions. NEUROLOGY 1999;52:798–809 Preliminary reports in patients with medically in- tractable epilepsy have compared functional MRI (fMRI) with the Wada test for determining hemi- sphere dominance for language in adults 1,2 and children 3 preoperatively and in post-temporal lobec- tomized patients. 4 These methods have not yet been extended to patients with mass lesions, including congenital malformations and neoplasms. Methods that use regional laterality to infer hemispheric dom- inance 3,4 are less useful when a lesion encompasses that particular brain region or its mirror region in the other hemisphere. Furthermore, it is well docu- mented through ablation models (unilateral lesion studies, electrical stimulation) that essential lan- guage cortex is distributed throughout the perisyl- vian cortex. 5 In the last 10 years functional neuroimaging studies in PET 6 and fMRI 7,8 have re- vealed left lateralized activity in extrastriate cortical areas, related to single word reading, that is sup- ported by the clinical observation that lesions of the dominant occipital cortex are associated with alexia. 9 Avoiding postoperative language deficits has his- torically involved two invasive methods—the intra- carotid amobarbital test (Wada test), 10 which attempts to lateralize language to one hemisphere, and electrical cortical stimulation (ECS) for intra- hemispheric localization of language cortex. Despite its clinical usefulness for lateralization, the Wada test has important drawbacks, including invasive- ness, exclusions based on arterial anatomy, 11 and in- dividual variability in response to amobarbital. 12 fMRI, with high-speed 13,14 imaging techniques, has been used to study cognitive functions, including lan- guage. 3,4,15,16 Whole brain imaging methods, which are able to detect language activity throughout a hemisphere, 1,17 are analogous to the Wada test, which assays an entire hemisphere for language function. High-speed MRI techniques such as echo- planar MRI are capable of rapid, whole brain func- tional imaging and have already demonstrated the ability to accurately localize language in preopera- tive patients with a variety of perisylvian brain le- From the Department of Neurology (Dr. Benson), University of Connecticut Health Center, Farmington, CT; MGH-NMR Center, Department of Radiology (D.B. FitzGerald and Drs. Kennedy, Kwong, Buchbinder, Weisskoff, Belliveau, and Rosen), Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Neurology (Dr. Kennedy), Center for Morphometric Analysis, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Department of Electrical and Computer Engineering (Dr. Talavage), Purdue University; Division of Neurology (Dr. Logan), The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Neurosurgery (Dr. Cosgrove), Massachusetts General Hospital, Harvard Medical School, Charlestown, MA; Department of Neurology (Dr. LeSueur), Massachusetts General Hospital, Boston, MA; Mallinckrodt Institute of Radiology (Dr. Davis), Washington University Medical Center, St. Louis, MO; University of Massachusetts Medical School (Dr. FitzGerald), Worcester, MA. Supported by NIH Training Grant 5T32CA09502 and NIH grants R01-MH50054 and T35-HL07841-01A1. Received January 3, 1998. Accepted in final form November 21, 1998. Address correspondence and reprint requests to Dr. Randall R. Benson, University of Connecticut Health Center, Department of Neurology, 263 Farmington Avenue, Farmington, CT 06030-1845. 798 Copyright © 1999 by the American Academy of Neurology