Circuits and brain rhythms in schizophrenia: a wealth of convergent targets

Few common neurological illnesses trace back to single molecular disturbances. Many disparate putative causes may co-associate with a single disease state. However, uncovering functional, hierarchical networks of underlying mechanisms can provide a framework in which many primary pathologies converge on more complex, single higher level correlates of disease. This article focuses on cognitive deficits associated with schizophrenia to illustrate: a) How non-invasive EEG biomarkers of cognitive function constitute such a ‘higher level correlate’ of underlying pathologies. b) How derangement of multiple, cell-specific, molecular processes can converge on such EEG-visible, correlates of disrupted cognitive function. This approach suggests that evidence-based design of multi-target therapies may take advantage of hierarchical patterns of convergence to improve both efficacy and selectivity of disease-intervention.

► In this article we consider the mechanisms underlying cognitive deficit in schizophrenia. ► We show that a hierarchy of dynamic processes contributes to the deficit. ► We illustrate the prospect of selective intervention at the level of brain dynamics: ‘rhythm repair’. ► Evidence reveals that many multireceptor actions of antipsychotics converge on interneuron function underlying gamma rhythms. ► We suggest that evidence-based polypharmacy may allow tailoring of therapy to individual patient needs.