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.

Figures

Figure 1.

a, b, Example of probabilistic category learning (a) and perceptual-motor control (b) trials.

Figure 2.

a–c, Cumulative percentage correct at each trial block during probabilistic category learning for whole sample of patients with schizophrenia (SC) and healthy participants (NC) (a), those patients with schizophrenia and healthy participants classified as good learners (b), and those patients with schizophrenia and healthy participants classified as poor learners (c).

Figure 3.

a–c, Frequency of participants using different strategies during probabilistic category learning for eight patients with schizophrenia (sc) and 16 healthy participants (nc) classified as good learners (a), 23 patients and nine healthy adults classified as poor learners (b), and eight patients matched to eight healthy participants classified as good learners (c). Optimal-cue strategy: predict the outcome most often associated with cue-card combination. Complex-cue strategy: respond suboptimally on basis of whole configuration of cues. Single-cue strategy: respond on the presence or absence of a single cue (disregarding all other cues). Singleton strategy: respond only to patterns that have only one cue present. No strategy: no detectable strategy.

Figure 4.

a, b, Main effects of condition across the four quartiles in healthy adults (a) and patients with schizophrenia (b) (extent threshold, k = 3 voxels, p < 0.005 uncorrected).

Figure 5.

a, b, Brain regions showing greater activation during probabilistic category learning in the whole sample of healthy participants (nc) relative to patients with schizophrenia (sc) (a) and the whole sample of patients with schizophrenia relative to healthy participants (b) (extent threshold k = 3 voxels, p < 0.005 uncorrected).

Figure 6.

a, b, Brain regions showing greater activation during probabilistic category learning in eight healthy participants (nc) versus eight patients with schizophrenia (sc) classified as good learners (a) and eight patients with schizophrenia versus eight healthy participants classified as good learners (b) (extent threshold k = 3 voxels, p < 0.005 uncorrected).