Hypo-activity of the dorsolateral prefrontal cortex relates to increased reaction time variability in patients with schizophrenia

Increased reaction time intra-subject variability (RT-ISV) in fast decision tasks has been confirmed in patients with schizophrenia and has been hypothesized to result from a deficit in the control of attention. Here, an attentional task and functional brain imaging were used to probe the neural correlates of increased RT-ISV in schizophrenia.Thirty patients and 30 age and sex matched controls performed the Eriksen flanker spatial attention task with concurrent measurement of brain activity using functional magnetic resonance imaging (fMRI). The behavioral measures included accuracy, mean, standard deviation of RT (RTSD), coefficient of variation of RT (RTCV) and ex-Gaussian model of RT distribution parameters (mu, sigma and tau).Larger mean RT and Ex-Gaussian mu was observed for patients compared to controls. The group difference was larger for incongruent (attentionally demanding) versus congruent trials confirming a deficit in the control of spatial attention for patients. Significant increase in RT-ISV measures (RTSD, sigma and tau) for patients compared to controls was observed and was not modulated by trial congruency. Attention modulation (congruency effect) resulted in activation of bilateral frontal and parietal areas that was not different between patients and controls. Right middle frontal, right superior temporal and bilateral cingulate areas were more active in controls compared to patients independent of congruency. Activation in ROIs extracted from attention (congruency) and group related areas correlated with RT-ISV measures (especially RTCV and tau). Hypo-activation of the right middle frontal area correlated with increased tau specifically in patients.Hypo-activity of the right prefrontal cortex predicted increased RT-ISV in schizophrenia. This effect was unrelated to the effects of spatial attention and might be linked to a deficit in the inhibitory control of action for these patients. Keywords: fMRI, Attention, Prefrontal cortex, Reaction time, Intra-subject variability, Psychosis