Irrelevance by inhibition: Learning, computation, and implications for schizophrenia

Abstract

Symptoms of schizophrenia may arise from a failure of cortical circuits to filter-out irrelevant inputs. Schizophrenia has also been linked to disruptions in cortical inhibitory interneurons, consistent with the possibility that in the normally functioning brain, these cells are in some part responsible for determining which sensory inputs are relevant versus irrelevant. Here, we develop a 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 the expected magnitude of reward or punishment (“relevance”), which can be trained using a temporal difference learning mechanism acting on feedforward inputs to inhibitory interneurons. In the model, irrelevant and blocked stimuli drive lower levels of excitatory activity compared with novel and relevant stimuli, and this difference in activity levels is lost following disruptions to inhibitory units. When excitatory units are connected to a competitive-learning output layer with a threshold, the relevance code can be shown to “gate” both learning and behavioral responses to irrelevant stimuli. 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.

Reduced learning rate and E/I imbalance drive Peripersonal Space boundaries expansion in Schizophrenia

“…This finding is consistent with the literature showing that E/I ratio is a marker of learning efficacy [72][73][74] and is necessary to stabilise trained perceptual learning from subsequent new learning by dynamically shifting from excitatory to inhibitory dominant processing [75]. Furthermore, failures in cortical inhibitory interneurons observed in SCZ are thought to be related to overlearning of irrelevant stimuli in the environment [76]. Speculatively, the sharper PPS representation observed after training under E/I imbalance conditions (see Fig.…”

Terminal type-specific cannabinoid CB1 receptor alterations in patients with schizophrenia: a pilot study

“…As PFC pathology is implicated in the cognitive dysfunctions of SZ, CB1R alterations may directly contribute to symptom development by disturbing the excitatory and inhibitory balance(68) -a mechanism known to contribute to impaired salience learning (69). Considering CB1R's role in suppressing neurotransmitter release, it is possible that these findings of higher CB1R levels in excitatory boutons of SZ represent a stronger suppression of excitatory neurotransmission (i.e., DSE).…”