Practice-induced changes in neural circuitries supporting saccade performance in schizophrenia

Abstract

Decreased prefrontal cortex (PFC) function is hypothesized as a key deficit in people with schizophrenia. PFC circuitry supports higher level executive control processes such as inhibition. A simple test of inhibition is provided by an antisaccade task, which requires a glance to the mirror image of a peripheral cue. People with schizophrenia make more antisaccade errors towards the cue and have lower PFC activity than healthy participants. The extent to which PFC activity may be enhanced to possibly improve executive control in schizophrenia is uncertain. Recent studies from our laboratory showed that in healthy people daily antisaccade practice improves antisaccade performance, while daily prosaccade practice disrupts antisaccade performance. These behavioral changes are accompanied by quantifiable changes in brain activation. The current study was designed to determine whether neural pathways supporting antisaccade performance in schizophrenia are modified across time. People with schizophrenia (SZ) and normal comparison subjects (NP) took part in a 2-week trial. Testing evaluated anti- and pro-saccade performance in a 3-Tesla fMRI environment at 3 time points, each separated by a week; 1) Pre-Test, 2) Mid-Test, and 3) Post-Test. Subjects were assigned to a practice group (either antisaccades or prosaccades) and between fMRI testing sessions completed daily practice sessions on the assigned task. In order to determine if improved executive functioning processes could be generalized beyond the practice task, other measures of executive function were evaluated before and after the practice trial using both saccade (ocular motor delayed response task – ODRT) and non-saccade tasks (the Wisconsin Card Sorting Test - WCST). The behavioral results showed that both the SZ and NP prosaccade practice groups demonstrated similar behavioral performance patterns across time (decreased latencies and sustained performance) while the SZ and NP antisaccade practice groups demonstrated incongruent patterns (the SZ group showed a trend for improved antisaccade performance with speed-accuracy tradeoffs while the NP group did not). The imaging results across groups illustrated typical saccadic circuitry in regions known to support antisaccade performance, and all groups demonstrated a trend for decreased PFC across time. Within the schizophrenia group, however, there was a small subset of participants who showed increased PFC activity from pre-test to post-test, and this reversal of hypofrontality was correlated with improved performance on various WCST measurements including, most notably, a decrease in rate of perseverative errors.