This study will investigate if children with schizophrenia (Sz) and complex partial seizure disorder (CPS) with thought disorder (i.e., illogical thinking, loose associations, impaired cohesion and repair) have distinct patterns of dysfunction in neuroanatomical structures and pathways involved in higher level linguistic processing. Findings in Sz adults, Sz children, and CPS children suggest that illogical thinking, loose associations, and impaired cohesion and repair might reflect impairment at different nodes in these networks during brain development. Using structural and functional magnetic resonance imaging (MRI), the proposed study will define these neural pathways, identify the structural and functional abnormalities underlying each of these thought disorder manifestations, and show how they are specifically impaired in childhood Sz and CPS. It will test the model that networks encompassing Wernicke's area, Broca's area, the left dorsolateral prefrontal cortex, and their right hemisphere homologues are involved in how children use language to formulate coherent and cohesive thoughts while speaking and to make sense of conversation (i.e., discourse coherence). More specifically, it will examine if distinct patterns of morphometric abnormalities in superior temporal gyrus, dorsolateral prefrontal cortex, and inferior frontal gyrus are associated with specific thought disorder symptoms in Sz and CPS subjects. Using fMRI, it will also determine if networks of cortical activity involving these regions are aberrant during discourse coherence, semantic, and syntactic tasks, with reduced activation in frontal regions in Sz and in temporal regions in CPS. It will investigate if the hypothesized morphometric abnormalities and aberrant patterns of cortical activity in these regions are associated with distinct patterns of deficits in memory, executive function, and language in the Sz and CPS subjects. This 4-year study will include 140 children with 40 Sz, 40 CPS, and 60 normal age and gender matched children, aged 7 - 14 years. The procedures administered to each child include collection of speech samples for coding thought disorder; testing of IQ, memory executive function, language, and handedness; structural MRI; and fMRI with discourse coherence, semantics, and syntax activation paradigms. Identification of the specific neuroanatomical structures and pathways involved in the thought disorder of children with Sz and CPS will make important scientific and clinical contributions. First, it will bridge an important gap in our knowledge of: a) the neuroanatomical mechanisms of how children use language to organize their thoughts coherently and cohesively and to make sense of conversation, and, b) the vulnerability of these mechanisms to childhood onset disorders, such as Sz and CPS. Second, the morbidity, chronicity, and cost to society of Sz in both adults and children underscore the importance of identifying mechanisms of thought disorder, a core symptom of Sz. Third, pediatric neurologists and mental health clinicians will become aware of the impact of CPS on brain development and on children's higher level linguistic skills. Finally, the findings would underscore the need for future pharmacological and social intervention studies targeted at preventing higher level linguistic deficits and improving the communication skills of children with Sz and CPS.
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