Neuroanatomy of substantia nigra and ventral tegmental area dopaminergic, and dorsal raphe serotonergic circuits in the human brain using T1-weighted and diffusion magnetic resonance imaging: A morphometric pilot study with estimate of reliability

Introduction We present here a methodology for morphometric analysis of the substantia nigra (SN), the ventral tegmental area (VTA), the dorsal raphe nucleus (DRN) and their respective structural brain circuits. Methods Our analyses were based on multimodal T1-weighted MRI and diffusion MRI (dMRI) segmentation and tractography in 12 human subjects drawn from the Human Connectome Project (HCP) repository. Results We were able to demonstrate strong connections of the SN, VTA and DRN with several brain regions, in particular the dorsolateral prefrontal cortex (DLPFC) and the cerebellum. More specifically, we created comprehensive visualizations of the SN and VTA dopaminergic as well as the DRN serotonergic structural circuits in the human brain, which, although preliminary, demonstrate the potential of multimodal neuroimaging to investigate these circuits quantitatively in clinical conditions. Finally, we created a pilot dataset for the most frequently observed structural connections, specifically those that were present more than 92% of the time among all subjects. Discussion: This pilot morphometric report examines the structural circuits of the SN, VTA and DRN, which are critically involved in several biobehaviors and clinical conditions such as addiction, stress, Parkinson’s disease (PD), schizophrenia, obsessive-compulsive disorder, post-traumatic stress disorder, attention deficit hyperactivity disorder, mood disorders, COVID-19 and long COVID. Importantly, the strong structural connectivity of the DLPFC and cerebellum with the SN, VTA and DRN is expected to be a potential target of noninvasive neuromodulation treatments in neuropsychiatry. Our findings demonstrate the potential of current clinical multimodal neuroimaging to delineate the dopaminergic (DA) and serotonergic (5-HT) circuits in the human brain in clinical conditions.