Impairments in feedback processing and reinforcement learning appear to be prominent aspects of schizophrenia (SZ), which may relate to symptoms of the disorder. Evidence from cognitive neuroscience investigations indicates that disparate brain systems may underlie different kinds of feedback-driven learning. The ability to rapidly shift response tendencies in the face of negative feedback, when reinforcement contingencies are reversed, is an important type of learning thought to depend on ventral prefrontal cortex (PFC). Schizophrenia has long been associated with dysfunction in dorsolateral areas of PFC, but evidence for ventral PFC impairment in more mixed. In order to assess whether SZ patients experience particular difficulty in carrying out a cognitive function commonly linked to ventral PFC function, we administered to 34 patients and 26 controls a modified version of an established probabilistic reversal learning task from the experimental literature [Cools, R., Clark, L., Owen, A.M., Robbins, T.W., 2002. Defining the neural mechanisms of probabilistic reversal learning using event-related functional magnetic resonance imaging. J. Neurosci. 22, 4563–4567]. Although SZ patients and controls performed similarly on the initial acquisition of probabilistic contingencies, patients showed substantial learning impairments when reinforcement contingencies were reversed, achieving significantly fewer reversals [χ2(6) = 15.717, p = 0.008]. Even when analyses were limited to subjects who acquired all probabilistic contingencies initially (22 patients and 20 controls), patients achieved significantly fewer reversals [χ2(3) = 9.408, p = 0.024]. These results support the idea that ventral PFC dysfunction is a prevalent aspect of schizophrenic pathophysiology, which may contribute to deficits in reinforcement learning exhibited by patients. Further studies are required to investigate the roles of dopaminergic systems in these impairments.
One of the most common neuropsychological findings in the schizophrenia (SZ) literature is that of impaired attentional set-shifting, as evidenced by studies using tasks like the Wisconsin Card Sort Test (WCST) and the intradimensional/extradimensional (ID/ED) attentional set-shifting task. This deficit has often been linked to dysfunction of dorsolateral prefrontal cortex (DLPFC), one of the most frequently-observed neural correlates of schizophrenia (Weinberger et al., 1986 and Berman et al., 1988). One possible source of set-shifting deficits in patients may be set-learning impairments related to limitations in DLPFC-dependent attentional and working memory resources. Another possible source of set-shifting difficulties, however, may be a specific impairment in reversing learned associations. The reversal of learned associations is known to depend on ventral and medial areas of prefrontal cortex (PFC) from a variety of studies involving both human and nonhuman animal subjects, including both lesion studies ( Dias et al., 1996, Fellows and Farah, 2003 and Hornak et al., 2004) and those using physiological data acquisition ( Rolls et al., 1996, Cools et al., 2002 and Evers et al., 2005). It is thought that ventral PFC contributes to the rapid reversal of learned associations through the integration and online representation of the reinforcement value of stimuli and actions ( Rolls, 1996, Roesch and Olson, 2005 and Schoenbaum and Roesch, 2005), while areas of medial prefrontal cortex, such as anterior cingulate cortex (ACC), figure critically in the monitoring of performance and detection of errors, processes which lead to behavioral modifications ( Carter et al., 1998, Paulus et al., 2002 and Holroyd et al., 2004).