The neuroreceptors and transporters underlying spontaneous brain activity.
Communications biology – July 30, 2025
Source: PubMed
Summary
Our brains' spontaneous activity, crucial for thought, is driven by complex interactions of neuroreceptors. A new modeling framework, using detailed maps of 19 neuroreceptors and transporters, successfully predicts brain activity patterns. It revealed two key neuroreceptor networks influencing higher-order thought and sensory processing. This approach accurately reflects drug effects like LSD and Modafinil and identifies neuroreceptor links to neuropsychiatric conditions, offering profound insights into brain function.
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.