Introduction

Neuropsychological evidence and clinical observations have repeatedly, directly or indirectly, implicated the prefrontal cortex as a site of dysfunction in schizophrenia – based on the similarity of impairments observed in demented patients and those with frontal lobe damage (e.g., Farkas et al., 1984; Levin, 1984a, 1984b; Weinberger et al., 1986; Goldman-Rakic, 1987, 1991). Although such findings have significantly advanced the empirical support for the “frontal-lobe” hypothesis, countless other results in the literature leave considerable room for doubt about any singular explanation for this heterogeneous disorder. Whatever the status of prefrontal involvement in schizophrenia, basic studies of its structure and function have provided support for two major conclusions: Prefrontal cortex is specialized to direct or guide behavior by internalized representations of facts, events and other memoranda (Goldman-Rakic, 1987), and prefrontal cortex carries out its functions through interactions within a complex distributed network of reciprocating pathways (Goldman-Rakic, 1988a, 1988b; Selemon and Goldman-Rakic, 1988; Goldman-Rakic et al., 1993).

It has been argued elsewhere that guiding behavior by representations – ideas and concepts – normally requires working memory and that schizophrenic thought disorder could involve a breakdown in this basic capacity for “on line” processing (Goldman-Rakic, 1987; 1991).