Etiology of Working Memory Deficit in Schizophrenia

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DESCRIPTION (provided by applicant): Neurocognitive deficits are core features of schizophrenia (SZ) that may determine functional outcome. Working memory (WM) deficit has been identified as one of the most important components of the neurocognitive deficits in SZ. WM is a limited-capacity, active short-term memory system that guides and controls behavior. A majority of SZ patients and about half of their healthy first-degree relatives have WM deficits and these deficits are linked to poor social and adaptive functioning yet the origins and consequences of WM deficit are unclear. Thus it has not been possible to develop targeted interventions that might ameliorate WM deficits and improve adaptive functioning. The present proposal seeks support to investigate components of WM deficits in SZ from a cognitive neuroscience approach, to identify the factors are central to WM deficit, their neural correlates and the effects of WM deficit on social functioning. Cognitive and neuroanatomical data suggest that selective attention and affect modulate encoding and maintenance in WM but SZ patients are unable to effectively integrate attention and affect to guide goal-directed behavior. In Study 1, the roles of perceptual, attentional and affective factors in encoding will be examined to specify both optimal and detrimental encoding conditions with a series of cognitive experiments. Encoding affects all forms of memory and thus has far-reaching consequences. In addition to impaired encoding there is good evidence for abnormal maintenance in SZ. In Study 2, the effects of attentional control and affect on maintenance will be examined to identify where vulnerabilities of SZ lie. In Study 3, the roles of prefrontal and parietal cortices in normal and abnormal WM will be investigated with even-related fMRI experiments. The neural correlates of correct and incorrect performance will be observed to elucidate the difference between remembering and forgetting in the brain. In sum, the current proposal aims to identify the key components of WM deficits in SZ subjects, and their unaffected siblings. Identification and elucidation of core neurocognitive deficits of SZ will contribute towards the understanding of the complex interplay between cortical functions and cognitive deficits in SZ. Moreover, specifying abnormal mechanisms within WM in relation to attention, affect and brain activation patterns could lead to targeted strategies that might ameliorate WM deficits and improve adaptive functioning in SZ.