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Substantia nigra is an important neuronal structure, located in the ventral midbrain, that exerts a regulatory function within the basal ganglia circuitry through the nigro-striatal pathway. Although its subcortical connections are relatively well-known in human brain, little is known about its cortical connections. The existence of a direct cortico-nigral pathway has been demonstrated in rodents and primates but only hypothesized in humans. In this study, we aimed at evaluating cortical connections of substantia nigra in vivo in human brain by using probabilistic constrained spherical deconvolution (CSD) tractography on magnetic resonance diffusion weighted imaging data. We found that substantia nigra is connected with cerebral cortex as a whole, with the most representative connections involving prefrontal cortex, precentral and postcentral gyri and superior parietal lobule. These results may be relevant for the comprehension of the pathophysiology of several neurological disorders involving substantia nigra, such as parkinson's disease, schizophrenia, and pathological addictions.

Previous Diffusion Tensor Imaging studies have demonstrated that the human red nucleus is widely interconnected with sensory-motor and prefrontal cortices. In this study, we assessed red nucleus connectivity by using a multi-tensor model called non- negative Constrained Spherical Deconvolution (CSD), which is able to resolve more than one fiber orientation per voxel. Connections of the red nuclei of fifteen volunteers were studied at 3T using CSD axonal tracking. We found significant connectivity between RN and the following cortical and subcortical areas: cerebellar cortex, thalamus, paracentral lobule, postcentral gyrus, precentral gyrus, superior frontal gyrus and dentate nucleus. We confirmed that red nucleus is tightly linked with the cerebral cortex and has dense subcortical connections with thalamus and cerebellar cortex. These findings may be useful in a clinical context considering that RN is involved in motor control and it is known to have potential to compensate for injury of the corticospinal tract.