Extensive Direct Subcortical Cerebellum-Basal Ganglia Connections in Human Brain as Revealed by Constrained Spherical Deconvolution Tractography

Abstract

The connections between the cerebellum and basal ganglia were assumed to occur at the level of neocortex. However evidences from animal data have challenged this old perspective showing extensive subcortical pathways linking the cerebellum with the basal ganglia. Here we tested the hypothesis if these connections also exist between the cerebellum and basal ganglia in the human brain by using diffusion magnetic resonance imaging and tractography. Fifteen healthy subjects were analyzed by using constrained spherical deconvolution technique obtained with a 3T magnetic resonance imaging scanner. We found extensive connections running between the subthalamic nucleus and cerebellar cortex and, as novel result, we demonstrated a direct route linking the dentate nucleus to the internal globus pallidus as well as to the substantia nigra. These findings may open a new scenario on the interpretation of basal ganglia disorders.

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). …”

Thalamic interactions of cerebellum and basal ganglia

“…For the subthalamic nucleus, recent findings reveal the existence of an anatomical substrate for the bidirectional communication between cerebellum and basal ganglia, as shown in rats (Ichinohe et al 2000) and monkeys (Bostan et al , 2013 sending disynaptic projections to the cerebellar cortex by way of the pontine nuclei. Similar evidence has been recently reported in the human brain (Pelzer et al 2013;Milardi et al 2016), consciously that these techniques are not able to dissolve direct synaptic relay. Next to a direct basal ganglia-cerebellar communication, the dentate nucleus sends efferent projections to the subthalamic region via red nucleus.…”

“…Nevertheless, next to putatively overlapping regions, however, also direct communication in the human brain between basal ganglia and cerebellum, via the internal part of the pallidum, has been described by (Milardi et al 2016;Pelzer et al 2013), which is in accordance with transneuronal tracing studies in nonhuman primate studies (Hoshi et al 2005).…”

Structural connectivity‐based topography of the human globus pallidus: Implications for therapeutic targeting in movement disorders

“…15,16 More recently, we used constrained spherical deconvolution (CSD)-based tractography, a diffusion MRI-based technique allowing in vivo reconstruction of connectivity patterns between nervous structures, [17][18][19][20][21] to study the human analogues of the above-mentioned direct cortico- 22 and dento-pallidal projections. 23 These connections, likely paralleled by analogue cortico- 24 and dento-nigral 23,25 pathways, may exert a converging influence of cerebral and neocerebellar cortex on the basal ganglia output nuclei.…”