The neuroreceptors and transporters underlying spontaneous brain activity

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 framewor...

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Main Authors: Johan Nakuci, Kanika Bansal
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08492-z
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author Johan Nakuci
Kanika Bansal
author_facet Johan Nakuci
Kanika Bansal
author_sort Johan Nakuci
collection DOAJ
description 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.
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spelling doaj-art-0cd4e47d94994e11a0c9c03952e28b6b2025-08-20T03:46:21ZengNature PortfolioCommunications Biology2399-36422025-07-018111510.1038/s42003-025-08492-zThe neuroreceptors and transporters underlying spontaneous brain activityJohan Nakuci0Kanika Bansal1U.S. ARMY DEVCOM Army Research Laboratory, Aberdeen Proving GroundU.S. ARMY DEVCOM Army Research Laboratory, Aberdeen Proving GroundAbstract 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.https://doi.org/10.1038/s42003-025-08492-z
spellingShingle Johan Nakuci
Kanika Bansal
The neuroreceptors and transporters underlying spontaneous brain activity
Communications Biology
title The neuroreceptors and transporters underlying spontaneous brain activity
title_full The neuroreceptors and transporters underlying spontaneous brain activity
title_fullStr The neuroreceptors and transporters underlying spontaneous brain activity
title_full_unstemmed The neuroreceptors and transporters underlying spontaneous brain activity
title_short The neuroreceptors and transporters underlying spontaneous brain activity
title_sort neuroreceptors and transporters underlying spontaneous brain activity
url https://doi.org/10.1038/s42003-025-08492-z
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