Cognitive impairment and associated frontal lobe dysfunction characterize schizophrenia. The letter fluency test (LFT) has been used as one of the most sensitive measures of the cognitive dysfunction, but the nature and topography of the hypofrontality have yet to be fully elucidated. In this study we used multi-channel near-infrared spectroscopy (NIRS), a recently developed noninvasive functional imaging technique, to measure changes in the concentration of oxygenated hemoglobin in the prefrontal cortices of 31 schizophrenia patients and 26 age- and sex-matched healthy controls during performance of the LFT. The results demonstrated reduced prefrontal cortex activation during the LFT among the schizophrenia patients in comparison with the healthy controls, even after controlling for medication. The hypofrontality was most salient in the prefrontal ventrolateral subregion bilaterally. The reduced activity appeared to be due not only to the lesser magnitude but also to the lesser fluctuation of the changes in oxygenated hemoglobin concentration. The hypofrontality appeared to be independent of the patients' symptomatological manifestations. We concluded that measuring NIRS during performance of the LFT can detect prefrontal lobe dysfunction of schizophrenia patients and may provide a new tool to monitor their treatment and course.
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