Aberrant Learned Irrelevance in Patients with First-Episode Schizophrenia-Spectrum Disorder

Emerging evidence has indicated disrupted learned irrelevance (LIrr), a form of selective attention deficit that may contribute to psychotic symptom formation, in schizophrenia. However, previous research mostly focused on chronic patients. There is a paucity of studies on LIrr in first-episode schizophrenia-spectrum disorder (i.e., schizophrenia and schizophreniform disorder; FES), which were limited by small sample size and have produced mixed results. The current study examined a LIrr effect and its relationship with positive symptom severity in 40 briefly-medicated FES patients and 42 demographically-matched healthy controls using a well-validated computerized LIrr paradigm which has been applied in chronic schizophrenia sample. Positive symptoms were assessed by Positive and Negative Syndrome Scale (PANSS) and Psychotic Symptom Rating Scales (PSYRATS). Our results showed that controls demonstrated intact LIrr, with significantly faster learning about previously predictive (relevant) than previously non-predictive (irrelevant) cues. Lack of such normal attention bias towards predictive over non-predictive cues was observed in FES patients, indicating their failure to distinguish between relevant and irrelevant stimuli. Nonetheless, we failed to reveal any significant correlations between learning scores, in particular learning scores for non-predictive cues, and positive symptom measures in FES patients. Learning scores were also not associated with other symptom dimensions, cognitive functions and antipsychotic dose. In conclusion, our findings indicate aberrant LIrr with impaired allocation of attention to relevant versus irrelevant stimuli in briefly-medicated FES patients. Further prospective research is warranted to clarify the longitudinal trajectory of such selective attention deficit and its association with positive symptoms and treatment response in the early course of illness.

Relevance learning via inhibitory plasticity and its implications for schizophrenia

Symptoms of schizophrenia may arise from a failure of cortical circuits to filter-out irrelevant inputs. Schizophrenia has also been linked to disruptions to cortical inhibitory interneurons, consistent with the possibility that in the normally functioning brain, these cells are in some part responsible for determining which inputs are relevant and which irrelevant. Here, we develop an abstract but biologically plausible neural network model that demonstrates how the cortex may learn to ignore irrelevant inputs through plasticity processes affecting inhibition. The model is based on the proposal that the amount of excitatory output from a cortical circuit encodes expected magnitude of reward or punishment (”relevance”), which can be trained using a temporal difference learning mechanism acting on feed-forward inputs to inhibitory interneurons. The model exhibits learned irrelevance and blocking, which become impaired following disruptions to inhibitory units. When excitatory units are connected to a competitive-learning output layer, the relevance code is capable of modulating learning and activity. Accordingly, the combined network is capable of recapitulating published experimental data linking inhibition in frontal cortex with fear learning and expression. Finally, the model demonstrates how relevance learning can take place in parallel with other types of learning, through plasticity rules involving inhibitory and excitatory components respectively. Altogether, this work offers a theory of how the cortex learns to selectively inhibit inputs, providing insight into how relevance-assignment problems may emerge in schizophrenia.

Learned Irrelevance and Cue Competition Using an Eriksen Flanker Task

Many studies have examined competition between cues for learning. Research examining cue competition has used cues that predict the occurrence of an outcome, or, in some rare cases, competition between cues that predict the absence of an outcome (predicting that an outcome explicitly will not occur). Alternatively, learned irrelevance occurs when a cue lacks the ability to predict the occurrence or absence of an outcome. Using an Eriksen flanker task, the present study evaluated competition among cues that do not have predictive value, that is, competition for learning that an outcome is unpredictable. Subjects’ inability to predict the occurrence of compatible and incompatible trials was manipulated by presenting cues that were uncorrelated with these trial types. Accuracy results showed competition between cues possessing a lack of predictive ability. The results are discussed in terms of propositional and associative theories of learning.