325. Functional MRI and formal thought disorder

Abstract

Formal thought disorder is a disabling symptom of schizophrenia, the neural basis of which is not established. Theories explaining this phenomenon implicate dysfunction in frontal lobe and temporo-parietal regions. We sought to interrogate the semantic system in schizophrenics and matched controls while studying brain activity using functional MRI. We employed a novel paradigm which requires subjects to associate features of objects to the (un-named) objects themselves (e.g.: “honey” + “stings” = “bee”). Typed feature pairs are presented visually via a back-projection system and subjects responded by pressing a button if the constituent features combined to suggest a specific object. A task wherein the features do not combine to yield an object was also employed. In 8 normal subjects (6 right-handed; 2 left-handed), the feature-to-object “verbal bind” was specifically associated with activation in lateral occipital gyrus, anterior cingulate gyrus, and middle and superior frontal lobe regions. These regions of activation may be elements of a cortico-cortical network subserving the assessment of a unique “solution” to the problem of construing a single object from certain constituent features. We are presently employing this paradigm in schizophrenics with varying severity of thought disorder. Prior evidence suggests the abnormal “spread” of associations occur in the semantic network of individuals with formal thought disorder and preliminary work indicates individuals with schizophrenia both incorrectly associate unrelated features and fail to correctly combine legitimately associated features. We hypothesize that schizophrenics will show activation abnormalities in the cortical regions described above and this abnormal activation reflects underlying network abnormalities.