Altered Patterns of Reward Activation in a Large Cohort of Antipsychotic Naïve First Episode Schizophrenia Patients

BACKGROUND
Disturbances of the brain reward system are suggested to play an important role in the development of central psychopathological symptoms in schizophrenia. Several studies have been published by know looking at dysfunctions of the reward system. Often these studies are driven by specific hypotheses trying to link a certain aspect of reward processing to specific symptoms. However, reward processing is a complex mechanism, as it consists of several phases which interact. Thus deficit found in one part of the reward process might be secondary to other mechanism and aspects, which might not have been caught by the focused analyses. By using a multivariate approach we want to confirm previous findings in a smaller group of patients, and further we expect this method to reveal other important alterations in reward processing.

METHODS
53 antipsychotic-naïve first-episode patients with schizophrenia and 48 age and gender matched healthy controls were included in a large first episode study. Among several other examinations, the participants went through a functional Magnetic Resonance Imaging (fMRI) while playing a monetary reward task.
The functional images were analyzed using the multivariate approach called partial least squares (PLS). This method was used in order to find functionally connected patterns in a whole brain context. PLS have the benefit that it does not analyze specific contrasts or compare groups. Instead the PLS analysis identifies new variables (latent variables) which explain the covariance of conditions and brain activity. The significance of each latent variable is determined by a permutation test. For the analyses a total of 17 conditions were defined; 2 conditions related to group and 15 conditions related to the reward paradigm (6 describing anticipation phase, 2 describing the action phase, and 7 describing the outcome phase)

RESULTS
The analyses found 30 LV of which 7 were highly significant. In LV 1 and LV2 were primarily describing covariance of the brain activity explained by the different conditions of the paradigm, and there were no group differences. LV 3, 4 and 5 were describing covariance which explained by group differences.
LV 3 described areas in the brain related to group differences during the anticipation evoked by uncertain cues, and during outcome evaluation of certain gain, certain loss and uncertain loss. Among these areas were parts of striatum and medial and dorso-lateral prefrontal cortex
LV 4 described a widespread network with group difference related the period right after the action applied to target when the outcome was uncertain.
LV 5 defined among others small areas in medial prefrontal and anterior cingulated cortex which were related to group differences during outcome evaluation of unexpected missed gain and unexpected loss but also related to neutral outcome .

DISCUSSION
The results of these analyses can be divided in two parts. First some of the findings confirm our own previous more hypothesis specific findings from a smaller group, where we previously demonstrated pronounced group differences during anticipation of salient events.
Second, they results give us new information about reward processing. There seem to be a changed pattern of deactivation rust after the action related to salient events. Further it demonstrated several changes during outcome evaluation, particularly in relation to unexpected outcome. This is very much in line with the idea of an altered prediction error response. Finally our analyses suggest that the schizophrenia patients might even have a different evaluation of a neutral outcome.