Molecular connectivity studies in neurotransmission: a scoping review

Purpose: Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are essential molecular imaging tools for the in vivo investigation of neurotransmission. Traditionally, PET and SPECT images are analysed in a univariate manner, testing for changes in radiotracer binding in regions or voxels of interest independently of each other. Over the past decade, there has been an increasing interest in the so-called molecular connectivity approach that captures relationships of molecular imaging measures in different brain regions. Targeting these inter-regional interactions within a neuroreceptor system may allow to better understand complex brain functions. In this article, we provide a comprehensive review of molecular connectivity studies in the field of neurotransmission. We examine the expanding use of molecular connectivity approaches, highlighting their applications, advantages over traditional methods, and contributions to advancing neuroscientific knowledge. Methods: A systematic search in three bibliographic databases MEDLINE, EMBASE and Scopus on July 14, 2023, was conducted. A second search was rerun on April 4, 2024. Molecular imaging studies examining functional interactions across brain regions were included based on predefined inclusion and exclusion criteria. Results: Thirty-nine studies were included in the scoping review. Studies were categorised based on the primary neurotransmitter system being targeted: dopamine, serotonin, opioid, muscarinic, glutamate and synaptic density. The most investigated system was the dopaminergic and the most investigated disease was Parkinson’s disease (PD). Conclusions: This review highlighted the diverse applications and methodologies in molecular connectivity research, particularly for neurodegenerative diseases and psychiatric disorders. Molecular connectivity research offers significant advantages over traditional methods, providing deeper insights into brain function and disease mechanisms. As the field continues to evolve, embracing these advanced methodologies will be essential to understand the complexities of the human brain and improve the robustness and applicability of research findings in clinical settings.