Mapping Mesolimbic Dopamine Projections to Subcortical Circuits Underlying Adaptive Behavior: A Human 7T Diffusion Tractography Atlas

Abstract

The mesolimbic dopamine system supports broad aspects of adaptive behavior including salience, learning, memory, and decision making, yet the structural organization supporting these functions remains incompletely mapped in humans. Using high-resolution 7T diffusion magnetic resonance imaging (up to N=173), we reconstructed seven bilateral ventral tegmental area (VTA)–subcortical pathways spanning direct mesolimbic projections and the hippocampus–VTA (HPC–VTA) loop regulatory circuit. Projection-endpoint analyses revealed long-axis and subfield organization of VTA–hippocampal pathways and superior-inferior VTA–nucleus accumbens (NAc) topography. Consistent with the HPC–VTA loop framework, neurite density covaried across mesolimbic pathways but not the arcuate fasciculus, demonstrating circuit-level organization. Nodewise analyses identified localized associations between pathway microstructure and delay discounting across VTA–hippocampal, VTA–NAc, and VTA– amygdala pathways. Together, these findings parse the human mesolimbic system into distinct pathways supporting adaptive behavior. The probabilistic atlas, MesoConnect, is freely available with tutorials to facilitate reconstruction and investigation of circuits in independent datasets.