Impaired prefrontal activity to regulate the intrinsic motivation-action link in schizophrenia

Abstract

A core feature of schizophrenia (SCZ) is impairment in intrinsic motivation. Although intrinsic motivation plays an important role in enhancing improvement of the social functioning, its neural mechanisms of impairment have yet to be clarified. We hypothesized that abnormal function of the frontostriatal loop consisting of the striatum and lateral prefrontal cortex (LPFC) may be related to impaired intrinsic motivation in SCZ. We tested this by comparing the brain activity measured by functional magnetic resonance imaging and behavioral parameters associated with movement, motivation, and cognitive control between 18 stable SCZ patients and 17 healthy control (HC) participants during a task that elicits intrinsic motivation. We also compared the functional connectivity during resting-state and the fractional anisotropy using diffusion tensor imaging analysis between the two groups. We adopted an enjoyable timing task to stop a stopwatch at an exact time, which in our previous study has demonstrated to elicit intrinsic motivation. Although the performance level in general was not different between groups, the SCZ group performed worse than the HC group in trials following “overshoot” errors (i.e., the response was too late). SCZ participants showed lower intrinsic motivation to the task than the HC group in an inventory report. The striatal activity during the prediction at the task cue period was consistently lower in SCZ participants than in HC. The LPFC activity at the task cue period positively correlated with intrinsic motivation and also with the rate of success following overshoot errors in the HC group, but not in the SCZ group. The LPFC activity at the task cue period was also positively correlated with the striatal activity in both groups. The striatal activity during the feedback period was not significantly different between groups. These results suggest that, unlike HC, the neural activity in the LPFC fails to mediate between prediction of hedonic events and cognitive control of action plans in SCZ, whereas the hedonic response is retained. Keywords: Cognitive control, Functional magnetic resonance imaging, Intrinsic motivation, Lateral prefrontal cortex, Schizophrenia, Striatum