The use of different imaging modalities provides the clinician and researcher with different views of anatomy and physiology at unprecedented levels of detail. Multimodal imaging allows for noninvasive measurement of structure and function in humans during complex behavior, and thus provides information about the inner workings of the brain previously unavailable. The present paper examines the various imaging techniques available, and describes their application to the clinic—in the case of epilepsy—and to research—in the case of schizophrenia. Because the electroen-cephalogram has a dynamic response in milliseconds, it provides the best temporal sensitivity of functional measures of brain activity. When coupled with high-resolution magnetic resonance imaging measures of brain structure, this multimodal approach provides a powerful tool for understanding brain activity. Clinically, the use of multimodal imaging has provided greater precision in localization of the epileptogenic focus. For researchers attempting to determine the underlying causes of schizophrenia, the use of multimodal imaging has helped lead the field away from a specific lesion view to a more distributed system abnormality view of this disorder.

Deficits in language comprehension in schizophrenia were examined using event-related potentials (ERPs). Schizophrenic and healthy participants read sentences in which the first clause ended with a homograph, and the second clause started with a target word that was semantically related to the homograph's dominant meaning (e.g., 1. Diving was forbidden from the bridge because the river had rocks in it. or 2. The guests played bridge because the river had rocks in it.). Processing of the targets (e.g., “river”) was expected to be primarily influenced by the preceding overall sentence context (congruent in 1; incongruent in 2) in healthy participants, but to be inappropriately affected by the dominant meaning of homographs (e.g., the “structure” meaning of “bridge”) in sentences like 2 in schizophrenic patients. The N400 ERP component that is known to be sensitive to contextual effects during language processing confirmed these predictions. This showed that language abnormalities in schizophrenia may be related to deficient processing of context-irrelevant semantic representations of words from the discourse.

Both the amplitude and latency of P300 vary with changes in stimulus parameters. Stimuli at intensities or pitch separations near threshold evoke a smaller and later P300. P300 is also affected by extraneous stimulus parameters in tasks where stimulus frequency separation is large and stimuli are well above intensity thresholds. For example, the presence of background white noise when tones are suprathreshold and easily detectable has been reported to increase P300 latency. However, the effects of background masking noise on P300 amplitude and scalp topography have not been reported. Subjects performed an oddball task both in the presence and in the absence of background noise. Performance accuracy was unaffected by background noise. P300 showed latency increases when noise was present, but P300 peak amplitude was unaffected. P300 scalp topography was stable across both conditions. P300 latency is affected by background noise, even when performance is not, but amplitude and amplitude topography remain unaffected.

Thought disorder in schizophrenia may involve abnormal semantic activation or faulty working memory maintenance. Event-related potentials (ERPs) were recorded while sentences reading “THE NOUN WAS ADJECTIVE/VERB” were presented to 34 schizophrenic and 34 control subjects. Some nouns were homographs with dominant and subordinate meanings. Their sentence ending presented information crucial for interpretation (e.g., The bank was [closed, steep]). Greatest N400 activity to subordinate homograph-meaning sentence endings in schizophrenia would reflect a semantic bias to strong associates. N400 to all endings would reflect faulty verbal working memory maintenance. Schizophrenic subjects showed N400 activity to all endings, suggesting problems in contextual maintenance independent of content, but slightly greater N400 activity to subordinate endings that correlated with the severity of psychosis. Future research should help determine whether a semantic activation bias in schizophrenia toward strong associates is reflected in ERP activity or whether this effect is overshadowed by faulty verbal working memory maintenance of context.

Event-related potentials (ERPs) provide a noninvasive method to evaluate neural activation and cognitive processes in schizophrenia. The pathophysiological significance of these findings would be greatly enhanced if scalp-recorded ERP abnormalities could be related to specific neural circuits and/or regions of the brain. Using quantitative approaches in which scalp-recorded ERP components are correlated with underlying neuroanatomy in schizophrenia, we focused on biophysical and statistical procedures (partial least squares) to relate the auditory P300 component to anatomic measures obtained from quantitative magnetic resonance imaging. These findings are consistent with other evidence that temporal lobe structures contribute to the generation of the scalp-recorded P300 component and that P300 amplitude asymmetry over temporal recording sites on the scalp may reflect anatomic asymmetries in the volume of the superior temporal gyrus in schizophrenia.