Neural networks involved in nausea in adult humans: A systematic review

Nausea is a common clinical symptom, poorly managed with anti-emetic drugs. To identify potential brain regions which may be therapeutic targets we systematically reviewed brain imaging in subjects reporting nausea. The systematic review followed PRISMA statements with methodological quality (MINORS) and risk of bias (ROBINS-I) assessed. Irrespective of the nauseagenic stimulus the common (but not only) cortical structures activated were the inferior frontal gyrus (IFG), the anterior cingulate cortex (ACC) and the anterior insula (AIns) with some evidence for lateralization (Left-IFG, Right-AIns, Right-ACC). Basal ganglia structures (e.g., putamen) were also consistently activated. Inactivation was rarely reported but occurred mainly in the cerebellum and occipital lobe. During nausea, functional connectivity increased, mainly between the posterior and mid- cingulate cortex. Limitations include, a paucity of studies and stimuli, subject demographics, inconsistent definition and measurement of nausea. Structures implicated in nausea are discussed in the context of knowledge of central pathways for interoception, emotion and autonomic control. Comparisons are made between nausea and other aversive sensations as multimodal aversive conscious experiences.