Apical integration theory provides a neural basis for understanding disorganization and consciousness in the schizophrenias

Curr Res Neurobiol. 2026 Jul 24;11:100165. doi: 10.1016/j.crneur.2026.100165. eCollection 2026 Dec.

ABSTRACT

Recent discoveries involving pyramidal neurons with two zones of input integration (apical and basal), the contextual information they provide, and the neural circuitry and neuromodulation systems in which they are embedded, can contribute to our understanding of disorganized symptoms in schizophrenia, including changes in their expression from the prodromal to chronic stages of the disorder. We demonstrate that the concepts and findings inherent to apical integration theory provide evidence in support of some of the seminal understandings of schizophrenia. In particular, considering the functions of two-point neurons allows for a novel neurobiological understanding of both their role in integrating different sources of information and the impairments in integrative functions that have long been hypothesized to be a defining characteristic of schizophrenia. We demonstrate how the weakening of integrative functions, in multiple domains including perception, cognition, language, behavior, and phenomenology, can be understood as arising from: 1) failures of apical dendrite activity to exert modulatory effects on neuronal output, and 2) reduced activity in the cortico-thalamic networks that support this form of contextual modulation. Later sections address topics such as implications of our view for understanding consciousness in schizophrenia, limitations, and future directions.

PMID:42571445 | PMC:PMC13452318 | DOI:10.1016/j.crneur.2026.100165