Cortical pruning and the development of schizophrenia: a computer model.

Schizophrenic patients tend to demonstrate reduced cerebral metabolism in frontal areas. Studies of human brain development reveal that synapses in the cerebral cortex are progressively reduced throughout childhood and adolescence, with parallel reductions in cerebral metabolism. This relationship is not surprising, since synaptic density is a primary factor determining regional metabolic requirements. The elimination of synapses in prefrontal cortex continues for a particularly long period of time, extending well into adolescence. Thus, reduced frontal metabolism in schizophrenic patients could be due to a developmental process--namely, elimination of synapses--gone too far. Animal studies indicate that developmentally induced reductions in synaptic density are due to the pruning of axonal collaterals rather than the death of neurons, which raises a critical question: Does excessive axonal pruning have specific pathological effects on cortical information processing? To answer this question, computer simulations of neural information processing systems were subjected to axonal pruning which reduced synaptic density. If pruning was conducted overzealously, cognitive pathology was induced that could, in humans, lead to the conscious experience of hallucinations, delusions, and Schneiderian symptoms.