A Direct Cortico-Nigral Pathway as Revealed by Constrained Spherical Deconvolution Tractography in Humans

Abstract

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.

The Olfactory System Revealed: Non-Invasive Mapping by using Constrained Spherical Deconvolution Tractography in Healthy Humans

“…These data extend previous works showing that CSD is a robust technique for the in vivo reconstruction of the intricate and complex brain networks (Lambert et al, 2012; Arrigo et al, 2014; Milardi et al, 2015a,b, 2016a,b; Mormina et al, 2015; Cacciola et al, 2016, 2017). …”

“…Using this approach, we have recently shown that a consistent reconstruction of the basal ganglia, red nucleus, claustrum and limbic connectome is feasible (Arrigo et al, 2014; Milardi et al, 2015a,b, 2016a,b; Mormina et al, 2015; Cacciola et al, 2016, 2017). …”

A Connectomic Analysis of the Human Basal Ganglia Network

“…Furthermore, we showed tractographic evidence of a complementary direct cortico-substantia nigra (SN) pathway paralleling the direct, indirect, hyperdirect, and cortico-pallidal systems (Cacciola et al, 2016a ). Several studies revealed cortico-nigral connections in rodents (Sesack et al, 1989 ), primates (Frankle et al, 2006 ) and humans (Kwon and Jang, 2014 ; Cacciola et al, 2016a ). Although in animals it was shown that this direct pathway may represent a glutamatergic cortical regulator of SN activity (Kornhuber et al, 1984 ), in humans its function and physiological significance are still unknown.…”

The many facets of motor learning and their relevance for Parkinson's disease

“…This system was paralleled by a di-synaptic afferent pathway from sensorimotor, associative, and limbic territories of the subthalamic nucleus to the posterior aspects of Crus II and the hemispheric lobule VIIB of the cerebellar cortex, passing through the pontine nuclei (Hoshi et al 2005; Bostan et al 2010). Importantly, recent work with diffusion tensor imaging and tractography reconstruction has confirmed, in vivo , in humans, the presence of extensive connections between the basal ganglia and cerebellum, including the existence of sub-cortical pathways running between the subthalamic nucleus and the cerebellar cortex via the pons (Cacciola et al 2016), with a possible direct route linking the dentate nucleus to the globus pallidum and the substantia nigra (Cacciola et al 2016). The existence of direct cerebellum-pallidal and cerebellum-nigral pathways may provide, in humans, a short-latency route for fast interaction between the cerebellum and the basal ganglia to harmonize their outputs in real-time (Cacciola et al 2017) and thus to provide the bases for their co-activation, which has been shown in motor learning studies with fMRI.…”