The Imbalanced Plasticity Hypothesis of Schizophrenia-Related Psychosis: A Predictive Perspective

Abstract

A considerable number of studies have attempted to account for the psychotic aspects of schizophrenia in terms of the influential predictive coding (PC) hypothesis. We argue that the prediction-oriented perspective on schizophrenia-related psychosis may benefit from a mechanistic model that: 1) gives due weight to the extent to which alterations in short-and long-term synaptic plasticity determine the degree and the direction of the functional disruption that occurs in psychosis; and 2) addresses the distinction between the two central syndromes of psychosis in schizophrenia: disorganization and reality-distortion. To accomplish these goals, we propose the Imbalanced Plasticity Hypothesis -IPH, and demonstrate that it: 1) accounts for commonalities and differences between disorganization and reality distortion in terms of excessive (hyper) or insufficient (hypo) neuroplasticity, respectively; 2) provides distinct predictions in the cognitive and electrophysiological domains; and 3) is able to reconcile conflicting PC-oriented accounts of psychosis.

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

“…In general, our findings on the neural mechanisms that drive PPS plasticity in SCZ are compatible with current theoretical accounts suggesting that schizophrenia symptomatology originates from increased synaptic plasticity due to abnormal regulation of NMDARs by neurotransmitters such as dopamine, serotonin, or acetylcholine [42,43,56]. The observed reduction in learning rate could be associated with altered dopaminergic prediction error signals observed in the prelimbic-hypothalamic-striatal circuits [57,77].…”

“…We also encourage the design of novel experimental paradigms that aim to measure the short-and long-term plasticity of PPS [56]. Such paradigms should also be designed to clarify the active or passive nature of the learning process that drives the plasticity of PPS.…”

“…In general, this line of research suggests that memory and learning deficits are a key aspect of cognitive dysfunction in patients with schizophrenia and play a key role in the origin of positive and negative symptoms observed in the disease [42,43,54]. However, there is a lack of understanding of how difficulties in learning and "overlearning" (of irrelevant/neutral information) coexist in the disease [55][56][57].…”