This proposal will use functional magnetic resonance imaging (fMRI) to assess early auditory processing, verbal semantic processing, and their association with positive symptoms in first episode (FE), chronic schizophrenic (CSZ), and matched control subjects (CN). These studies are aimed at understanding the link between brain dysfunction and symptoms, thus facilitating the discovery of preventative measures and treatments. The superior temporal gyrus (STG) plays a major role in auditory speech perception and language processing. This region is consistently reported to show volume reductions in MRI studies of schizophrenic subjects (SZ). These volume reductions have been linked to auditory hallucinations, thought disorder, and auditory event-related potential (ERP) abnormalities. Left STG abnormalities are also consistently shown in functional imaging studies of active hallucination or of auditory-verbal processing in SZ. Abnormal fMRI activity in the STG in chronic SZ was found using mismatch negativity (MMN) stimuli that were similar to those used in an ERP paradigm. Recent discoveries have documented structural and functional evidence for the basis of language lateralization in normal individuals. We will use these recent discoveries, in a rapid acoustic processing task (RAP), in addition to the MMN task, as a basis for proposed studies examining early auditory processing in SZ. Lateral temporal (middle, inferior) and temporal-parietal regions are thought to play a role in semantic processing. These regions have also shown abnormalities in functional imaging and ERP studies of schizophrenia that use language. Semantic priming has been shown (although not consistently) in a number of studies to be abnormal in SZ. A recent behavioral study used words that differed in terms of the properties of their semantic networks. The reduced performance of SZ subjects on the cued recall of words was attributed to the effects of abnormal connectivity in the semantic network but not network size. SZ and CN subjects will be tested in an fMRI study of auditory/verbal semantic priming. This study will examine the brain activity related to the spreading activation between semantic associates. Words will vary in the degree of connectivity, and hence the degree of spreading activation between their associates. A recently completed preliminary study of CN subjects used this semantic priming task (SP) and found that as predicted, different patterns of brain activity in temporal lobe regions were associated with different semantic properties (connectivity and relatedness) of the word pairs.
