Neural Correlates of Probabilistic Category Learning in Patients with Schizophrenia

Abstract

Functional neuroimaging studies of probabilistic category learning in healthy adults report activation of cortical-striatal circuitry. Based on previous findings of normal learning rate concurrent with an overall performance deficit in patients with schizophrenia, we hypothesized that relative to healthy adults, patients with schizophrenia would display preserved caudate nucleus and abnormal prefrontal cortex activation during probabilistic category learning. Forty patients with schizophrenia receiving antipsychotic medication and 25 healthy participants were assessed on interleaved blocks of probabilistic category learning and control tasks while undergoing blood oxygenation level-dependent functional magnetic resonance imaging. In addition to the whole sample of patients with schizophrenia and healthy adults, a subset of patients and healthy adults matched for good learning was also compared. In the whole sample analysis, patients with schizophrenia displayed impaired performance in conjunction with normal learning rate relative to healthy adults. The matched comparison of patients and healthy adults classified as good learners revealed greater caudate and dorsolateral prefrontal cortex activity in the healthy adults and greater activation in a more rostral region of the dorsolateral prefrontal, cingulate, parahippocampal and parietal cortex in patients. These results demonstrate that successful probabilistic category learning can occur in the absence of normal frontal-striatal function. Based on analyses of the patients and healthy adults matched on learning and performance, a minority of patients with schizophrenia achieve successful probabilistic category learning and performance levels through differential activation of a circumscribed neural network which suggests a compensatory mechanism in patients showing successful learning.

Goal Representations and Motivational Drive in Schizophrenia: The Role of Prefrontal-Striatal Interactions

“…However, these differences were apparent throughout the course of the task and did not vary as a function of learning rate or time on task, raising questions as to the specific processes that they reflected. 146 In a related study, Koch et al 138 found reduced activation among individuals with schizophrenia in DLPFC and ACC in a probabilistic learning paradigm when the predictability of reward outcomes was low. Furthermore, these researchers also found reduced positive prediction error responses in frontal cortex, cingulate, and putamen.…”

“…Weickert et al 146 found that controls showed greater activation than individuals with schizophrenia in both DLPFC and caudate. This was true even when analyses were restricted to a subset of controls and patients considered to be good learners.…”

“…Numerous studies have shown what appears to be a relatively intact learning rate in schizophrenia, coupled with overall impaired performance. [141][142][143][144][145][146] In other words, individuals with schizophrenia start out the task more impaired, learn at relatively the same rate as controls (but see these for evidence of an exception 147,148 ), yet never reach the same asymptotic level of performance. There is some evidence that reinforcement learning may be more intact for patients on atypical than typical antipsychotics, though it has been found in those on typicals as well.…”

Mechanisms Underlying Motivational Deficits in Psychopathology: Similarities and Differences in Depression and Schizophrenia

“…However, the evidence suggests surprisingly intact performance on a range of tasks in which learning is either relatively easy or relatively implicit (Elliott et al 1995;Hutton et al 1998;Joyce et al 2002;Turner et al 2004;Tyson et al 2004;Jazbec et al 2007;Waltz and Gold 2007;Ceaser et al 2008;Heerey et al 2008;Weiler et al 2009;Somlai et al 2011), though with some exceptions (Oades 1997;Pantelis et al 1999). Further, individuals with schizophrenia show intact learning rates on the weather prediction task, a probabilistic category-learning task frequently used to measure reinforcement learning, though with overall impaired performance (Keri et al 2000(Keri et al , 2005aWeickert et al 2002Weickert et al , 2009Beninger et al 2003). There is some evidence that reinforcement learning may be more intact for patients on atypical than typical antipsychotics, though it has been found in those on typicals as well (Beninger et al 2003;Keri et al 2005a, b).…”

Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state

“…34 Other authors assessing patients with schizophrenia also found differential activation patterns in frontal-striatal-thalamic regions during probabilistic learning or reward prediction tasks. [35][36][37] Imaging techniques in general might be able to unravel the neurobiological alteration during ARMS. In a review, Wood and colleagues 38 concluded that an activation of the stress system and an increased striatal dopamine synthesis seem to be a marker of ARMS patients most at risk for later transition to psychosis, but huge variations in methodology must be noted.…”