A wide range of abnormalities in thought processes characterizes schizophrenia. Loose associations a condition in which associations among cognitive elements do not follow the cohesive structure found in normal individuals, is one of the cardinal features of this syndrome. Functionally, abnormalities have been found in a number of different brain regions in schizophrenia. This suggests that associative thought disorder in schizophrenia might be understood in terms of the interactions among widespread brain regions that mediate associations. This study is aimed at characterizing interactions among brain regions during single-word reading, both in schizophrenia and in normal function. Reading is a task that is known to tap into a wide range of associations. More generally, strings of letters or symbols, depending on their content and arrangement, can have a variety of associations ranging from semantic, phonological and lexical familiarity associated with real words to the purely visual properties in strings of unfamiliar symbols. The goal of this study is to perform an in-depth investigation into how interactions among widespread regions of the brain mediate cognitive associations in schizophrenia by using reading tasks with four different types of strings that vary in their similarity to real words. The study includes 3 segments: 1) Identification of the networks that mediate the tasks in normal volunteers and in patients with schizophrenia; 2) Computation of the interactions among the components of this network and assessment of how they differ between the two groups; and 3) Examination of how associations are formed when subjects are familiarized with initially unfamiliar strings. This research will lead to a better understanding of language disorganization in schizophrenia. In conjunction with the research, the educational activities proposed will prepare me to begin independent clinical research using both behavioral and pharmacological manipulations. This combined research and educational approach may enhance drug development with respect to specific interacting elements of the brain, and may promote an improvement in schizophrenia treatment strategies.
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