The insular cortex and cardiovascular system: a new insight into the brain-heart axis

Abstract

The classical literature on neurocardiology has focused mainly on the subcortical regions of the central autonomic nervous system. However, recent studies have supported the notion that the cardiovascular system is regulated by cortical modulation. Modern neuroimaging data, including positron emission tomography and functional magnetic resonance imaging, have revealed that a network consisting of the insular cortex, anterior cingulate gyrus, and amygdala plays a crucial role in the regulation of central autonomic nervous system. Because the insular cortex is located in the region of the middle cerebral arteries, its structure tends to be exposed to a higher risk of cerebrovascular disease. The insular cortex damage has been associated with arrhythmia, diurnal blood pressure variation disruption (eg, a non-dipper or riser pattern), myocardial injury, and sleep disordered breathing, as well as higher plasma levels of brain natriuretic peptide, catecholamine, and glucose. This review article focuses on the role of the insular cortex as a mediator for the cardiovascular system and summarizes current knowledge on the relationships between cerebrovascular disease and cardiovascular system dysregulation. Finally, a hypothesis of the neural network involved in cortical cardiovascular modulation, including modulation of the insular cortex, is provided.

Introduction

The literature on neurocardiology has focused mainly on the subcortical regions of the central autonomic nervous system. In the 1980s, Hachinski et al reported an association between cortical stroke lesions and cardiovascular dysregulation.¹ Recent studies have supported the notion that the cardiovascular system is regulated by cortical modulation. Modern neuroimaging data, including positron emission tomography and functional magnetic resonance imaging (fMRI) data, have revealed that a network consisting of the insular cortex, anterior cingulate gyrus, and amygdala is necessary for regulation of the central autonomic nervous system. Because the insular cortex is located in the region of the middle cerebral arteries, its structure tends to be exposed to a higher risk of cerebrovascular disease (Figure 1). In clinical studies, the insular cortex damage has been associated with arrhythmia, diurnal blood pressure (BP) variation disruption (eg, a nondipper or riser pattern), myocardial injury, and sleep-disordered breathing, as well as higher plasma levels of brain natriuretic peptide, catecholamine, and glucose.

From these points of view, this review article will focus on the physiology of the insular cortex in central autonomic nervous system regulation. To set the stage for this review, we first summarize the current insights on the brain-heart axis. Although the relationships of the insular cortex damage to sleep-disordered breathing² and impaired glucose tolerance³ are very important, these issues could not be included in this review because of space limitations.