Ventral tegmental area connections to motor and sensory cortical fields in humans.

In humans, sensorimotor cortical areas receive relevant dopaminergic innervation-although an anatomic description of the underlying fiber projections is lacking so far. In general, dopaminergic projections towards the cortex originate within the ventral tegmental area (VTA) and are organized in a meso-cortico-limbic system. Using a DTI-based global tractography approach, we recently characterized the superolateral branch of the medial forebrain bundle (slMFB), a prominent pathway providing dopaminergic (and other transmitters) innervation for the pre-frontal cortex (Coenen et al., NeuroImage Clin 18:770-783, 2018). To define the connections between VTA and sensory-motor cortical fields that should contain dopaminergic fibers, we use the slMFB as a key structure to lead our fiber selection procedure: using a similar tracking-seed and tractography algorithm, we describe a dorsal extension of this slMFB that covers sensorimotor fields that are dorsally appended to pre-frontal cortical areas. This "motorMFB", that connects the VTA to sensorimotor cortical fields, can be further segregated into three sub-bundles with a seed-based fiber-selection strategy: A PFC bundle that is attendant to the pre-frontal cortex, passes the lateral VTA, runs through the border zone between the posterior and lateral ventral thalamic nucleus, and involves the pre- and postcentral gyrus. An MB bundle that is attendant to the mammillary bodies runs directly through the medial VTA, passes the lateral ventral thalamic nucleus, and involves the pre- and postcentral gyrus as well as the supplementary motor area (SMA) and the dorsal premotor cortex (dPMC). Finally, a BC bundle that is attendant to the brainstem and cerebellum runs through the lateral VTA, passes the anterior ventral thalamic nucleus, and covers the SMA, pre-SMA, and the dPMC. We, furthermore, included a fiber tracking of the well-defined dentato-rubro-thalamic tract (DRT) that is known to lie in close proximity with respect to fiber orientation and projection areas. As expected, the tract is characterized by a decussation at the ponto-mesencephal level and a projection covering the superior-frontal and precentral cortex. In addition to the physiological role of these particular bundles, the physiological and pathophysiological impact of dopaminergic signaling within sensorimotor cortical fields becomes discussed. However, some limitations have to be taken into account in consequence of the method: the transmitter content, the directionality, and the occurrence of interposed synaptic contacts cannot be specified.