U. Bauer

Effective neuroleptic medication removes prepulse inhibition deficits in schizophrenia patients

BACKGROUND The magnitude of the startle eyeblink response is reduced if the startle eliciting stimulus is shortly preceded by another stimulus. There is evidence that schizophrenia patients exhibit impairments in this so-called prepulse inhibition. Our study investigated whether prepulse inhibition is affected by neuroleptic drug treatment as is suggested by animal research. METHODS Prepulse inhibition was tested in five unmedicated and 20 medicated inpatients with schizophrenia, and 12 normal controls. RESULTS The unmedicated schizophrenia patients showed a strong impairment of sensorimotor gating as indexed by the absence of prepulse inhibition. By contrast, the medicated patients showed a pronounced prepulse inhibition that did not differ from that of the normal controls. There was a substantial covariation between the rated severity of the positive syndrome and the amount of prepulse inhibition--i.e., the patients whose positive symptoms were rated as more severe showed less prepulse inhibition. CONCLUSIONS These data suggest that the impaired sensorimotor gating of schizophrenia patients is not a stable vulnerability indicator, but may rather be related to the positive syndrome and may be improved by treatments with neuroleptic medication.

Latent inhibition and schizophrenia: Pavlovian conditioning of autonomic responses

Latent inhibition (LI) is an important model for understanding cognitive deficits in schizophrenia. Disruption of LI is thought to result from an inability to ignore irrelevant stimuli. The study investigated LI in schizophrenic patients by using Pavlovian conditioning of electrodermal responses in a complete within-subject design. Thirty-two schizophrenic patients (16 acute, unmedicated and 16 medicated patients) and 16 healthy control subjects (matched with respect to age and gender) participated in the study. The experiment consisted of two stages: preexposure and conditioning. During preexposure two visual stimuli were presented. one of which served as the to-be-conditioned stimulus (CSp + ) and the other one was the not-to-be-conditioned stimulus (CSp - ) during the following conditioning ( = acquisition). During acquisition, two novel visual stimuli(CSn + and CSn - ) were introduced. A reaction time task was used as the unconditioned stimulus (US). LI was defined as the difference in response differentiation observed between preexposed and non-preexposed sets of CS + and CS - . During preexposure, the schizophrenic patients did not differ in electrodermal responding from the control subjects, neither concerning the extent of orienting nor the course of habituation. The exposure to novel stimuli at the beginning of the acquisition elicited reduced orienting responses in unmedicated patients compared to medicated patients and control subjects. LI was observed in medicated schizophrenic patients and healthy controls, but not in acute unmedicated patients. Furthermore LI was found to be correlated with the duration of illness: it was attenuated in patients who had suffered their first psychotic episode.

THE TOPOGRAPHY OF NON-LINEAR CORTICAL DYNAMICS AT REST, IN MENTAL CALCULATION AND MOVING SHAPE PERCEPTION

Differential cortical activation by cognitive processing was studied using dimensional complexity, a measure derived from nonlinear dynamics that indicates the degrees of freedom (complexity) of a dynamic system. We examined the EEG of 32 healthy subjects at rest, during a visually presented calculation task, and during a moving shape perception task. As a nonlinear measure of connectivity, the mutual dimension of selected electrode pairs was used. The first Lyapunov coefficient was also calculated. Data were tested for non-linearity using a surrogate data method and compared to spectral EEG measures (power, coherence). Surrogate data testing confirmed the presence of nonlinear structure in the data. Cognitive activation led to a highly significant rise in dimensional complexity. While both tasks activated central, parietal and temporal areas, mental arithmetic showed frontal activation and an activity maximum at T3, while the moving shape task led to occipital activation and a right parietal activity maximum. Analysis of mutual dimension showed activation of a bilateral temporal-right frontal network in calculation. The Lyapunov coefficent showed clear topographic variation, but was not significantly changed by mental tasks (p<.09). While dimensional complexity was almost unrelated to power values, nonlinear (mutual dimension) and linear (coherence) measures of connectivity shared up to 37% of variance. Data are interpreted in terms of increased cortical complexity as a result of recruitment of asynchronously active, distributed neuronal assemblies in cognition. The topography of nonlinear dynamics are related to neuropsychological and neuroimaging findings on mental calculation and moving shape perception.