The role of the anterior cingulate cortex in anxiety control, from circuits to disorders
TL;DR
A timely and comprehensive view of the anterior cingulate cortex’s role in adaptive and pathological anxiety is provided and an integrative model in which ACC effects depend on subregion, projection target, and behavioral context is proposed.
Abstract
Anxiety is an adaptive response essential for survival that integrates external stimuli, internal states, memory, and decision making to respond to perceived threats. When dysregulated, it can become excessive and persistent, contributing to psychiatric and neurological disorders. The anterior cingulate cortex (ACC) integrates cognitive, emotional, interoceptive, and autonomic information and serves as a key hub in anxiety-related circuits. However, its subregion- and pathway-specific roles remain incompletely integrated across species. This review examines the cytoarchitectural and cellular organization of ACC subregions and their proposed correspondence in humans, non-human primates, and rodents. We then review ACC connectivity with the amygdala, hippocampus, insula, and bed nucleus of the stria terminalis and propose an integrative model in which ACC effects depend on subregion, projection target, and behavioral context. We also summarize structural, functional, connectivity, and neurochemical alterations of the ACC in anxiety-related disorders and neurodegenerative diseases with prominent anxiety symptoms. Finally, we discuss the strengths and limitations of rodent and non-human-primate models and identify priorities for future mechanistic and translational studies. Together, this review provides a timely and comprehensive view of the ACC’s role in adaptive and pathological anxiety and offers a framework for advancing mechanistic and translational research.