An fMRI study of visual lexical decision in patients with schizophrenia and clinical high-risk individuals

Disturbances in semantic and phonological aspects of language processing are indicated in patients with schizophrenia, and in high-risk individuals for schizophrenia. To uncover neural correlates of the disturbances, a previous functional magnetic resonance imaging (fMRI) study using a visual lexical decision task in block design reported less leftward lateralization in the inferior frontal cortices, in patients with schizophrenia and individuals with high genetic risk for psychosis compared with normal control subjects. However, to our knowledge, no previous study has investigated contrasts between word and non-word processing that allow dissociation between semantic and phonological processing using event-related design visual lexical decision fMRI tasks in subjects with ultra-high-risk for psychosis (UHR) and patients with schizophrenia. In the current study, 20 patients with schizophrenia, 11 UHR, and 20 demographically matched controls underwent lexical decision fMRI tasks. Compared with controls, both schizophrenia and UHR groups showed significantly decreased activity in response to non-words compared with words in the inferior frontal regions. Additionally, decreased leftward lateralization in the non-word compared with word activity contrast was found in subjects with UHR compared with controls, which was not evident in patients with schizophrenia. The present findings suggest neural correlates of difficulty in phonological aspects of language processing during non-word processing in contrast to word, which at least partially commonly underlies the pathophysiology of schizophrenia and UHR. Together with a previous study in genetic high-risk subjects, the current results also suggest that reduced functional lateralization in the language-related frontal cortex may be a vulnerability marker for schizophrenia. Furthermore, the current result may suggest that the genetic basis of psychosis is presumed to be related to the evolution of the language capacity characteristic of humans.