Prefrontal activation during verbal fluency tests in schizophrenia—a near-infrared spectroscopy (NIRS) study

Letter- or semantically-cued verbal fluency tests (VFT) induce different, but overlapping activities in the prefrontal cortex (PFC) in healthy subjects. Functional differences between letter and semantic VFT may be important in elucidating the nature of language-related problems in schizophrenia since more profound impairment in semantically-cued retrieval may be suggestive of semantic system dysfunction specific to this disorder. However, the functional differences between the letter vs. semantic VFT on prefrontal metabolism in the subjects with schizophrenia have not been described. In the present study, we used near-infrared spectroscopy (NIRS) to assess hemoglobin concentration changes in the bilateral PFCs in subjects and controls. Sixteen subjects with schizophrenia and 19 healthy controls performed letter and semantic VFTs. Prefrontal hemodynamic changes were simultaneously monitored by NIRS. While healthy subjects performed both tasks equivalently, the subjects with schizophrenia showed more compromised performance in the semantic VFTs compared to the letter VFTs. NIRS measurement revealed that the pattern of PFC activation was greater during the letter VFT when compared to the semantic VFT in the healthy subjects, suggesting more prominent PFC involvement in letter-cued retrieval. In contrast, the subjects with schizophrenia showed the opposite pattern of activation, implying that the semantic mode of lexical access might impose greater cognitive demands on the PFC. The present study is the first to detect abnormal patterns of PFC activation in adults with schizophrenia in response to the distinct cognitive demands associated with letter and semantic VFT.