The neuroreceptors and transporters underlying spontaneous brain activity.

A neuroreceptor-based modeling framework using cortical density maps of 19 neuroreceptors and transporters from PET scans can reconstruct BOLD-derived brain activity. The framework identified two neuroreceptor modules: one linked to higher-order associative networks and another to somatomotor and visual networks. Applied to independent datasets, it recovered the binding profiles of LSD and Modafinil, consistent with known pharmacology. It also uncovered associations between neuroreceptors and altered brain activity in neuropsychiatric disorders. The findings suggest the framework can elucidate neuromodulatory mechanisms and advance understanding of brain function across diverse states and conditions.

Study at a glance

Abstract

Determining the neuromodulators driving brain activity is critical for understanding cognition and neuropathology. Neuromodulators act through neuroreceptors in a coordinated manner, yet their interconnected dynamics are often overlooked. We show that a neuroreceptor-based modeling framework using cortical density maps of 19 neuroreceptors and transporters from Positron Emission Tomography (PET) can model BOLD-derived brain activity. This framework reconstructs activity across four datasets (N = 314) identifying two neuroreceptor modules linked to higher-order associative or somatomotor and visual networks. Applying the framework to independent datasets, we recover the binding profiles of LSD and Modafinil, demonstrating consistency with known pharmacological and neurobiological associations. Additionally, it uncovered associations between neuroreceptors, transporters, and altered brain activity in neuropsychiatric disorders. These findings demonstrate the framework's potential to elucidate neuromodulatory mechanisms and advance our understanding of brain function across diverse states and conditions.