High density of nicotinic receptors in the cingulo-insular network

• The density of heteromeric nicotinic receptors is not equal throughout the cortex.
• The insular and cingulate cortices are particularly rich in nicotinic receptors.
• The cingulo-insular functional network is especially rich in nicotinic receptors.
• The cingulo-insular network seems to have a particular neurochemical organization.
• The cingulo-insular nicotinic receptors could play a role in attentional control.

The nicotinic system plays an important role in ordinary cognition, particularly in attention. The main nicotinic receptor in the human brain is the heteromeric α4β2 neuronal nicotinic acetylcholine receptor (nAChR), which is distributed throughout the brain, with an especially high density in the thalamus and brainstem. Despite the important role of α4β2 nAChRs in various physiological functions and pathological conditions, their distribution in the human cortex remains poorly characterized. We assessed the in vivo distribution of α4β2 nAChRs in the human cortex in a group of seven non-smoking healthy subjects, using 2-[18F]F-A-85380 PET and a volume-of-interest-based analysis. We showed that cortical nAChR density was highest in the insular and anterior cingulate cortices. In functional magnetic resonance imaging studies, these two cortical regions and the thalamus have been shown to be highly correlated during the resting state and various tasks. Here, we also directly assessed nAChR density in this cingulo-insular network as defined in an independent dataset using resting-state functional connectivity, and compared it to other control-related networks, to the default mode network as well as to sensory and motor networks. Receptor density was significantly higher in the cingulo-insular network. This network has been suggested to maintain a variety of foundational capacities fundamental to cognitive function. The demonstration of a high nAChR density in the insular and anterior cingulate cortices reflects a particular neurochemical organization of the cingulo-insular network, and suggests an important role of the nicotinic receptors in its functions.