Functional neuroimaging of word priming in males with chronic schizophrenia

Abstract

Word-priming studies have suggested that the associative disturbance of schizophrenia may reflect aberrant spread of activation through the lexicon of the brain. To explore this, we examined lexical activation using a semantic word-priming paradigm coupled with functional magnetic resonance imaging (fMRI). We also wanted to determine whether brain activation to this paradigm correlated with relevant clinical symptom measures. In addition to completing clinical symptom measures, twelve chronic patients and twelve demographically matched control subjects completed a lexical-decision semantic-priming paradigm developed as an event-related BOLD fMRI task. This paradigm consisted of words that differed in connectivity. Words with many connections between shared semantic associates are considered high in connectivity and produce the largest behavioral semantic priming effects in control subjects, while words with few connections between shared semantic associates are considered low in connectivity and produce a relatively smaller amount of semantic priming. In fMRI, a respective step-wise increase in activation from high connectivity to low connectivity to unrelated word pairs was expected for normal subjects. Controls showed the expected pattern of activation to word connectivity; however, patients showed a less robust pattern of activation to word connectivity. Furthermore, this aberrant response correlated with measures of Auditory Hallucinations, Distractive Speech, Illogicality, and Incoherence. The patients did not display left frontal and temporal activation as a function of the degree of word connectivity as seen in healthy controls. This may reflect a disease-related disturbance in functional connectivity of lexical activation, which in turn may be associated with clinical symptomatology.

Figure 1

Examples of two lexical-semantic association networks that differ with respect to connectivity. The DINNER network is high in connectivity due to the greater number of associations that exist between associate words of the target word. The DOG network is low in connectivity due to the relatively fewer number of associations that exist between associate words of the target word.

Figure 2

Within-group and between-group (second level) activation differences regressed according to word connectivity in left temporal and frontal areas for control and schizophrenic subjects. Control subjects showed multiple areas of greater activation regressed according to word connectivity compared to schizophrenia patients. T value threshold at p=0.001, uncorrected.

Figure 3

Significant areas of activation after a regression analysis of the high connectivity < low connectivity < unrelated contrast with SAPS Illogicality, Incoherence, and Distractive Speech in schizophrenic subjects. T value threshold at p=0.001, uncorrected.

Figure 4

Significant areas of activation after a regression analysis of the high connectivity < low connectivity < unrelated contrast with SAPS Auditory Hallucinations in schizophrenic subjects. T value threshold at p=0.001, uncorrected.