The Joumal of Neuroscience,January 1,1997,17(1):353-362 Human Brain Language Areas Identified by Functional Magnetic Resonance Imaging Jeffrey R.Binder,12 Julie A.Frost,Thomas A.Hammeke,Robert W.Cox,3 Stephen M.Rao,2 and Thomas Prieto Departments of Neurology and 2Cellular Biology and Anatomy,and Biophysics Research Institute,Medical College of Wisconsin,Milwaukee,Wisconsin 53226 areas i the i I lobes I onsistent with classical r antic functi y to in the ory,mo and general executive functic ns The I nguage middle temporal,inferior temporal,fusiform,and angular gyri ed with a contro areas in a tas handed subiects.These maps were averaged in standard ste otaxic space to produ av or for ongoing cassCalmodesf1angageorganiaionAasedcnesion Language-related functions were among the first to be ascribed a Functional magnetic resonance imaging (FMRI)is one such on moni 100 mode of organization.based on data and rema s in co mmon use(Wemicke.17:Lichth Mayeux and Kandel, 1985 Binder et DeYoe et:Sereno et a1995) sive"area for planning and executing nctions o ha eech and writing m of sed an ts,nam d atter Broca (B the reliability of respones in these proc cedures remain unc accept this Sha witz et al. 1995) ed ot univ tic about aurall to clicit receptive anguage pro ciative of new data on languag with the goal as mar candidat (Petersen et al.,1988:Demonet et al..1992;Bottini et al.,1994) control for activation of early auditory ed Aur.1 1996:revised Oct.7.1996: ed0t.11,1996. tion and ar gical D natio J.Hyde.A.Je nd l a strong correlation en this s de otid amobarbital procedure(Binder et al. 1995.199 6b).Thes d in maging ion pHuman Brain Language Areas Identified by Functional Magnetic Resonance Imaging Jeffrey R. Binder,1,2 Julie A. Frost,1 Thomas A. Hammeke,1 Robert W. Cox,3 Stephen M. Rao,1,2 and Thomas Prieto1 Departments of 1Neurology and 2Cellular Biology and Anatomy, and 3Biophysics Research Institute, Medical College of Wisconsin, Milwaukee, Wisconsin 53226 Functional magnetic resonance imaging (FMRI) was used to identify candidate language processing areas in the intact hu￾man brain. Language was defined broadly to include both phonological and lexical–semantic functions and to exclude sensory, motor, and general executive functions. The language activation task required phonetic and semantic analysis of aurally presented words and was compared with a control task involving perceptual analysis of nonlinguistic sounds. Func￾tional maps of the entire brain were obtained from 30 right￾handed subjects. These maps were averaged in standard ste￾reotaxic space to produce a robust “average activation map” that proved reliable in a split-half analysis. As predicted from classical models of language organization based on lesion data, cortical activation associated with language processing was strongly lateralized to the left cerebral hemisphere and involved a network of regions in the frontal, temporal, and parietal lobes. Less consistent with classical models were (1) the existence of left hemisphere temporoparietal language ar￾eas outside the traditional “Wernicke area,” namely, in the middle temporal, inferior temporal, fusiform, and angular gyri; (2) extensive left prefrontal language areas outside the classical “Broca area”; and (3) clear participation of these left frontal areas in a task emphasizing “receptive” language functions. Although partly in conflict with the classical model of language localization, these findings are generally compatible with re￾ported lesion data and provide additional support for ongoing efforts to refine and extend the classical model. Key words: language; functional magnetic resonance imag￾ing; brain mapping; semantic; phonological; auditory cortex Language-related functions were among the first to be ascribed a specific location in the human brain (Broca, 1861) and have been the subject of intense research for well over a century. A “classical model” of language organization, based on data from aphasic patients with brain lesions, was popularized during the late 19th century and remains in common use (Wernicke, 1874; Lichtheim, 1885; Geschwind, 1971; Benson, 1985; Mayeux and Kandel, 1985). In its most general form, this model proposes a frontal, “expres￾sive” area for planning and executing speech and writing move￾ments, named after Broca (Broca, 1861), and a posterior, “recep￾tive” area for analysis and identification of linguistic sensory stimuli, named after Wernicke (Wernicke, 1874). Although many researchers would accept this basic scheme, a more detailed account of language organization has not yet gained widespread approval. There is not universal agreement, for example, on such basic issues as which cortical areas make up the receptive lan￾guage system (Bogen and Bogen, 1976) or on the specific linguis￾tic role of Broca’s area (Marie, 1906; Mohr, 1976). Noninvasive functional imaging methods are a potential source of new data on language organization in the intact human brain (Petersen et al., 1988; De´monet et al., 1992; Bottini et al., 1994). Functional magnetic resonance imaging (FMRI) is one such method, which is based on monitoring regional changes in blood oxygenation resulting from neural activity (Ogawa et al., 1990, 1992). Although certain technical issues remain to be resolved, the capabilities of FMRI for localizing primary sensory and motor areas are now well established (Kim et al., 1993; Rao et al., 1993; Binder et al., 1994b; DeYoe et al., 1994; Sereno et al., 1995). Preliminary studies of higher cognitive functions also have been reported, but the validity of the activation procedures used and the reliability of responses in these procedures remain unclear (Hinke et al., 1993; McCarthy et al., 1993; Cohen et al., 1994; Rueckert et al., 1994; Binder et al., 1995; Demb et al., 1995; Shaywitz et al., 1995). We used FMRI to investigate the cortical regions involved in language processing in normal, right-handed subjects. The linguis￾tic task, which required meaning-based decisions about aurally presented words, was designed to elicit receptive language pro￾cessing at both phonetic (speech perceptual) and semantic (asso￾ciative) levels, with the goal of identifying as many candidate “receptive language” areas as possible. A baseline task, which required pitch-based decisions about tone sequences, was used to control for activation of early auditory processors, nonspecific executive functions mediating attention and arousal, and motor response systems. Preliminary studies using this language task demonstrated left hemisphere lateralization of blood oxygenation responses and a strong correlation between this lateralization measure and language lateralization as determined by the intra￾carotid amobarbital procedure (Binder et al., 1995, 1996b). These preliminary studies investigated individual subject activation pat￾terns only and did not include imaging of medial brain regions. A Received Aug. 1, 1996; revised Oct. 7, 1996; accepted Oct. 11, 1996. This work was supported by a grant from the McDonnell-Pew Program in Cogni￾tive Neuroscience, National Institute of Neurological Diseases and Stroke Grant RO1 NS33576, and National Institute of Mental Health Grant PO1 MH51358. We thank J. Hyde, A. Jesmanowicz, W. O’Reilly, and L. Estkowski for discussion and technical assistance. Correspondence should be addressed to Dr. J. R. Binder, Department of Neurol￾ogy, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226. Copyright q 1996 Society for Neuroscience 0270-6474/96/170353-10$05.00/0 The Journal of Neuroscience, January 1, 1997, 17(1):353–362