Heteromodal Association Cortex in Schizophrenia

To the Editor: In a recent issue, Robert W. Buchanan, M.D., and colleagues (1) reported a study based on volumetric magnetic resonance imaging of the heteromodal association cortex in schizophrenia. They “found evidence of disruption of heteromodal association cortical areas involved in the neuroanatomy of language in patients with schizophrenia.” They found no differences in other “heteromodal” regions.

Although this is an interesting study, there appear to be inconsistencies regarding definitions of the region of interest, i.e., the heteromodal cortex. These inconsistencies affect some of the study’s findings.

Citing Mesulam (2), the article begins, “The heteromodal association cortex comprises primarily the prefrontal, superior temporal, and inferior parietal cortices.” The faceplates opposite page 12 of the Mesulam text (2) show the presumed full extent of the heteromodal association cortex in humans. They depict clearly the following:

Pages 32–49 of the Mesulam text (2) define further, in text form, the correct anatomical boundaries of heteromodal association cortices, as described.

Another point is that the posterior boundary of the prefrontal (heteromodal) cortex (including the inferior reaches targeted in this study) is not the precentral sulcus, as used by the authors. Rather, the boundary is the anterior border of the premotor (unimodal) cortex (2). Unlike the anterior border of the precentral gyrus, the prefrontal (heteromodal)/premotor (unimodal) border is not appreciable on structural magnetic resonance scans.

Thus, the data in the study by Dr. Buchanan and colleagues include measurements of substantial portions of the unimodal association cortex (premotor region and superior temporal gyrus) and do not take into account the heteromodal cortex in the middle temporal gyrus and superior parietal lobule. This affects some of the study’s findings, since the distinction between the heteromodal and unimodal association cortices are not purely semantic. For example, in single-unit recording experiments in primates, the neurons in the unimodal (auditory) association cortex respond primarily to auditory stimuli (2). By contrast, single-unit recordings in the heteromodal association cortex identify a broad array of cells. Some respond to only one type of sensory stimulus (auditory, visual, or somatosensory), others respond to two, and still others respond in all three sensory channels (2).

These issues do not discount the authors’ conclusion that the inferior parietal lobule is affected in schizophrenia but do temper claims such as negative findings in other heteromodal regions. In sum, the authors need to clarify their views on what constitutes the heteromodal association cortex in order to construct a richer study of it in schizophrenia.