Relative Shift in Activity from Medial to Lateral Frontal Cortex During Internally Versus Externally Guided Word Generation Bruce Crosson, Joseph R. Sadek, Leeza Maron, Didem Go ¨kc¸ay, Cecile M. Mohr, Edward J. Auerbach, Alan J. Freeman, Christiana M. Leonard, and Richard W. Briggs Abstract & Goldberg (1985) hypothesized that as language output changes from internally to externally guided production, activity shifts from supplementary motor area (SMA) to lateral premotor areas, including Broca’s area. To test this hypothesis, 15 right-handed native English speakers performed three word generation tasks varying in the amount of internal guidance and a repetition task during functional magnetic resonance imaging (fMRI). Volumes of significant activity for each task versus a resting state were derived using voxel-by-voxel repeated-measures t tests (p < .001) across subjects. Changes in the size of activity volumes for left medial frontal regions (SMA and pre-SMA/BA 32) versus left lateral frontal regions (Broca’s area, inferior frontal sulcus) were assessed as internal guidance of word generation decreased and external guidance increased. Comparing SMA to Broca’s area, Goldberg’s hypothesis was not verified. However, pre-SMA/BA 32 activity volumes decreased significantly and inferior frontal sulcus activity volumes increased significantly as word generation tasks moved from internally to externally guided. & How does the human brain initiate the expression of thought in language? A comprehensive understanding of the brain’s language systems necessitates an answer to this question. An appreciation of language initiation mechanisms could facilitate treatment development for language initiation deficits in aphasia. For some time, cognitive neuroscientists have known that the medial frontal cortex plays a role in language initiation. How- ever, the nature of this involvement has yet to be determined. Medial frontal lesions cause akinetic mutism, in which speech is initiated only with significant external prompting (Barris & Schuman, 1953; Nielson & Jacobs, 1951). Regarding the absence of spontaneous lan- guage, Luria’s (1966) report of a medial frontal lesion case indicated that thoughts were not present to express. This phenomenon suggests that the medial frontal cortex plays a role in initiating the cognitive aspects of spontaneous language. After evaluating em- pirical evidence on this subject, Picard and Strick (1996), Passingham (1993), and Goldberg (1985) con- cluded that the degree of involvement of medial frontal structures, and which medial structures partici- pate, depends upon the nature of the language that is initiated. Goldberg (1985) suggested that involvement of med- ial frontal cortex depends upon whether language is triggered by internal or external contingencies. He fo- cused on the divergent roles of the supplementary motor area (SMA) and lateral premotor cortex. Goldberg speculated that Broca’s area was prominent in the lateral premotor cortex of humans (p. 578), especially when considering language functions. Traditionally, Broca’s area has been designated as the posterior portion of the inferior frontal gyrus, i.e., pars opercularis (Brod- mann’s area [BA] 44) and pars triangularis (BA 45). Although recent literature indicates important functional divisions within medial BA 6 that might have influenced his conclusions (see below), SMA was considered to consist of the entire medial BA 6 at the time Goldberg wrote his review. He surmised that SMA was primarily involved in internally generated language and actions, whereas lateral premotor cortex was involved in lan- guage or actions that are externally referenced. Passingham’s (1993) subsequent review on medial versus lateral premotor cortex arrived at a similar con- clusion. In reference to selection of movement, Passing- ham believed that lateral premotor cortex made greater contributions when movements were driven by external cues, and medial premotor cortex played a greater role when no external cues were available (i.e., when move- ment was driven from internal models). However, Pas- singham (1993) also concluded that neither internally University of Florida © 2001 Massachusetts Institute of Technology Journal of Cognitive Neuroscience 13:2, pp. 272–283