Mapping Serotonergic Dynamics using Drug-Modulated Molecular Connectivity
Brain imaging plays a critical role in unraveling the complex functional architecture of animal and human brains. However, individual imaging modalities often face limitations confining them to narrow physiological perspectives. Our study introduces "Molecular connectivity" (MC), a novel concept in imaging that provides a detailed view of molecular interactions and their implications for brain functionality. This research bridges the gap between functional magnetic resonance imaging (fMRI) which tracks neurovascular dynamics, and positron emission tomography (PET), revealing molecular changes at the receptor level. The integration of these techniques can enhance our comprehension of brain-wide effects of drugs. In this study, we delve deeper into this integration by extracting molecular connectivity (MC) at the individual subject level using dynamic [11C]DASB PET scans, which map serotonin transporters (SERT). We particularly focus on assessing the ability of this method to track pharmacological alterations introduced by methylenedioxymethamphetamine (MDMA).

Our comprehensive analysis involves a comparison between MC and functional connectivity (FC), utilizing seed-based and independent component analysis (ICA) during resting states. We identified significant, physiologically pertinent independent components with the [11C]DASB data, thereby enhancing the interpretation of FC results. Remarkably, we observed pronounced changes in MC following a single MDMA administration with strong correlations between resting state MC and the spatial-temporal patterns of MDMAs effect on SERT occupancy.

This research marks a pioneering effort in investigating subject-level MC using PET imaging. Our findings suggests that these advanced imaging techniques can substantially refine our understanding of how drugs influence the overarching functional organization of the brain.