Fig. 5: Topographical relationship of OFC/vmPFC projection fiber terminals in the diencephalic-mesencephalic junction (summary).

The ORT (pink) presents itself as a DTI fiber selection belonging to the lateral slMFB. ORT additionally includes secondary neuronal connections to STN (and SN). A Three-dimensional reconstruction of a tract tracing from a single injection in a marmoset monkey (A13, orbitofrontal, example of OFC/vmPFC injections from [33, 81]. Limbic STN-direct (hyperdirect) connections were not replicated in this study. B, C Cartoonistic summary and integration into human anatomy. B Unconstrained DTI seeding approaches select lateral fibers of the slMFB which seem to enter the STN/SN region. After termination of descending glutamatergic fibers in the VTA, these fibers switch to neurons (interneurons, DA neurons) which in turn might connect to the STN (C). The fiber connection to the STN is therefore not a direct one but only picked up as such by DTI tractography which is agnostic for synapses or directionality (efferent or afferent) of the projection. D Demonstration of the medial/lateral limbic/motor gradient (arrow) with the SPECTRE [82] technology. Electrodes are located in the sensorimotor STN. Green coloring denotes more prefrontal (limbic) connectivity. Blue coloring denotes motor connectivity. Legend: viii, third ventricle; LH lateral hypothalamus, STN subthalamic nucleus, SN substantia nigra, SNc SN pars compacta, SNr SN pars reticulata, VTA ventral tegmental area, RN red nucleus, rrf retro-rubral field, mtt mammillothalamic tract, Fx fornix, MSR medial subthalamic region, DA Dopamine, Glu Glutamate, slMFB superolateral branch of the medial forebrain bundle, ORT unified connectomic pathway, DTI diffusion-tensor magnetic resonance imaging.