The insula: Leveraging cellular and systems-level research to better understand its roles in health and schizophrenia

Schizophrenia is a highly heterogeneous disorder characterized by a multitude of complex and seemingly non-overlapping symptoms. The insular cortex has gained increasing attention in neuroscience and psychiatry due to its involvement in a diverse range of fundamental human experiences and behaviors. This review article provides an overview of the insula's cellular and anatomical organization, functional and structural connectivity, and functional significance. Focusing on specific insula subregions and using knowledge gained from humans and preclinical studies of insular tracings in non-human primates, we review the literature and discuss the functional roles of each subregion, including in somatosensation, interoception, salience processing, emotional processing, and social cognition. Building from this foundation, we then extend these findings to discuss reported abnormalities of these functions in individuals with schizophrenia, implicating insular involvement in schizophrenia pathology. This review underscores the insula's vast role in the human experience and how abnormal insula structure and function could result in the wide-ranging symptoms observed in schizophrenia.