Performance on the Wisconsin Card Sort Test (WCST) of patients with schizophrenia, Parkinson's disease (PD), and Huntington's disease (HD) was simulated by a neural network model constructed on principles derived from neuroanatomic loops from the frontal cortex through the basal ganglia and thalamus. The model provided a computational rationale for the empirical pattern of perseverative errors associated with frontal cortex dysfunction and random errors associated with striatal dysfunction. The model displayed perseverative errors in performance when the gain parameter of the activation function in units representing frontal cortex neurons was reduced as an analog of reduced dopamine release. Random errors occurred when the gain parameter of the activation function in units representing striatal neurons was reduced, or when the activation level was itself reduced as an analog of a striatal lesion. The model demonstrated that the perseveration of schizophrenic, Huntington's, and demented Parkinsonian patients may be principally due to ineffective inhibition of previously learned contextual rules in the frontal cortex, while the random errors of Parkinson's and Huntington's patients are more likely to be due to unsystematic errors of matching in the striatum. The model also made specific, empirically falsifiable predictions that can be used to explore the utility of these putative mechanisms of information processing in the frontal cortex and basal ganglia.

The published literature does not support the contention that early intervention for psychosis reduces costs or achieves cost-effectiveness. Past failed attempts to reduce health costs by reducing hospitalization, and increased outpatient costs in early-intervention programmes suggest such programmes may increase costs. Future economic evaluation of early-intervention programmes would need to correctly value outpatient costs and accommodate uncertainty regarding reduced hospitalization costs, perhaps by sensitivity analysis. The current research hints that cost differences may be greater early in treatment and in patients with more severe illness.

SUMMARY1. The impulse activity of single neurones in the forelimb part of the motor cortex was recorded extracellularly in unrestrained cats during self-paced locomotion on a horizontal circular ladder.2. Fifty-one cells (forty-nine of which discharged rhythmically in time with the step cycle) were recorded during encounters with a number of rungs that could be locked firmly in position or, alternatively, held in position by weak springs so that when stepped on they unexpectedly descended (under the weight of the animal) from 1 to 5 cm before contacting a mechanical stop.3. In eleven cells (22 %) including four fast-axon pyramidal tract neurones (PTNs), an increase in discharge occurred when the contralateral forelimb descended unexpectedly. Onset latency relative to the start of rung movement ranged from ca 20 to ca 100 ms. In eight cells latency was such that most of the response preceded contact of the rung with the stop; averaged over a number of trials the altered discharge in five of these cells (including two PTNs) represented an accurate profile of the averaged velocity of rung (and foot) descent. The three remaining cells appeared to be responding largely to the cessation of rung movement.4. Thirty-six of the cells were also studied during unexpected descent of the ipsilateral forelimb and six (17 %) displayed an increase in discharge (onset latency ca 35 to ca 80 ms); three of these were among those that also responded to contralateral descents.5. These findings for skilled locomotion requiring a high degree of visuomotor coordination are discussed and it is concluded that the motor cortex is rapidly informed regarding unexpected perturbations delivered to the contralateral forelimb at the onset of stance and that changes are evoked in the pattern of impulse traffic descending via the pyramidal tract.MS 9872

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