Reading Anomalous Sentences: An Event-Related fMRI Study of Semantic Processing Kent A. Kiehl,* Kristin R. Laurens,† , ‡ and Peter F. Liddle‡ *Institute of Living at Hartford Hospital and Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; †Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; and ‡Division of Psychiatry, School of Community Health Sciences, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom Received March 5, 2001 We report a random-effects analysis of an event-re- lated fMRI study (n  28) of cerebral activity during the reading of sentences that ended with a word that was either congruent or incongruent with the previ- ous sentence context. Event-related potential studies have shown that this task elicits a late negativity peaking around 400 ms poststimulus (N400) that is larger for incongruent than for congruent sentence endings. A direct comparison of the activation for in- congruent words versus that for congruent words re- vealed significantly greater activation for incongruent words than congruent words in bilateral inferior fron- tal and inferio-medial temporal cortex, left lateral frontal cortex, left posterior fusiform gyrus, bilateral motor cortex, and supplementary motor area. These results are consistent with data from intracranial electrical recording studies of the N400 electrical potential. The results are discussed as they relate to the localization of the cerebral sites underlying se- mantic processing in general and the localization of the scalp recorded N400 event-related potential in particular. © 2002 Elsevier Science (USA) Key Words: semantic processing; sentence process- ing; event-related fMRI; fMRI; N400. INTRODUCTION For many years investigators have employed nonin- vasive measures of brain electrical activity to examine the temporal sequence and neural organization of lan- guage processing. This research has shown that sev- eral components of the event-related potential (ERP) are sensitive to linguistic processes. One component, the N400, a negative deflection in the ERP peaking at approximately 400 ms, can be elicited by words pre- sented in the absence of an appropriate sentence con- text (Kutas and Hillyard, 1980, 1982, 1983). The N400 is thought to reflect neural activity associated with processes related to semantic or lexical access of word representations (Kutas and Van Petten, 1994) or, al- ternatively, to processes integrating word representa- tions with current context (Holcomb, 1993). Subse- quent research has demonstrated that N400-like potentials are also elicited by nonverbal stimuli, such as faces and pictures (Barrett and Rugg, 1989, 1990). These latter findings raise the possibility that the N400 may reflect more general semantic processes. Interestingly, the N400 elicited by both semantically congruent and semantically incongruent sentence end- ings has been shown to be abnormal under a number of clinical conditions (e.g., schizophrenia), suggesting that it may index the aberrant neural activity charac- teristic of impaired thought processes (Niznikiewicz et al., 1997). Much is now known about the psychological processes mediating the elicitation of the N400. However, relatively little is known regarding the neural sources underlying its generation. Currently, the best data available on the neural generators of the N400 comes from invasive intra- cranial electrical field potential recordings from epilepsy patients undergoing presurgical assessment (Elger et al., 1997; Guillem et al., 1995; McCarthy et al., 1995; Smith et al., 1986). These studies have demonstrated that nega- tive field potentials in the 300- to 500-ms window are generated in a variety of cerebral sites. Using word-rec- ognition memory tasks, Smith et al. (1986) recorded stim- ulus-locked potentials in the medial temporal lobe, Elger et al. (1997) observed such potentials in both medial and lateral temporal lobe, and Guillem et al. (1995) recorded large-amplitude, polarity-inverted stimulus-locked po- tentials from various temporal, frontal, and parietal structures. In a study employing intracranial electrodes to record event-related field potentials during the pro- cessing of both congruent and incongruent sentence end- ings, McCarthy et al. (1995) found that the anomalous sentence-ending words elicited a large negative field po- tential with a peak latency near 400 ms, distributed bilaterally in the anterior medial temporal lobe near the amygdala. Subdural electrodes positioned near the col- lateral sulcus just inferior and lateral to the amygdala recorded a positive field potential at the same latency. NeuroImage 17, 842– 850 (2002) doi:10.1006/nimg.2002.1244 842 1053-8119/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.