Abstract
Deep gray matter nuclei are the synaptic relays, responsible to route signals between specific brain areas. Dentate nuclei (DNs) represent the main output channel of the cerebellum and yet are often unexplored especially in humans. We developed a multimodal MRI approach to identify DNs topography on the basis of their connectivity as well as their microstructural features. Based on results, we defined DN parcellations deputed to motor and to higher‐order functions in humans in vivo. Whole‐brain probabilistic tractography was performed on 25 healthy subjects from the Human Connectome Project to infer DN parcellations based on their connectivity with either the cerebral or the cerebellar cortex, in turn. A third DN atlas was created inputting microstructural diffusion‐derived metrics in an unsupervised fuzzy c‐means classification algorithm. All analyses were performed in native space, with probability atlas maps generated in standard space. Cerebellar lobule‐specific connectivity identified one motor parcellation, accounting for about 30% of the DN volume, and two non‐motor parcellations, one cognitive and one sensory, which occupied the remaining volume. The other two approaches provided overlapping results in terms of geometrical distribution with those identified with cerebellar lobule‐specific connectivity, although with some differences in volumes. A gender effect was observed with respect to motor areas and higher‐order function representations. This is the first study that indicates that more than half of the DN volumes is involved in non‐motor functions and that connectivity‐based and microstructure‐based atlases provide complementary information. These results represent a step‐ahead for the interpretation of pathological conditions involving cerebro‐cerebellar circuits.
Highlights
The brain is the principal organ of the nervous system and is composed of several different neuron types that are structurally and functionally well-organized to create specialized tissues (Voogd & Ruigrok, 2012)
Probabilistic tractography was used to parcellate dentate nuclei (DN) in humans on the basis of the cerebellar region that was mostly connected: motor rostrodorsal and non-motor ventro-caudal areas were identified. This was a promising result because supported the fact that the DNs present a topography reflecting different functional properties, but the main limit was that this study focused only on DN connectivity with the cerebellum instead of considering the whole-brain
Connectivity-based and microstructure-based topography atlases of the DNs were successful in demonstrating parcellations consistent with predicted expectations from animal work
Summary
The brain is the principal organ of the nervous system and is composed of several different neuron types that are structurally and functionally well-organized to create specialized tissues (Voogd & Ruigrok, 2012). Other gray matter structures, called deep gray matter nuclei, are identifiable within the white matter and are extremely important because they are synaptic relays, meaning that they represent areas where neurons make synapses achieving information transfer and integration. These regions are responsible to route signals, transported along the axons, to and from specific areas of the brain. This finding is in line with the recent understanding that the cerebellum is connected to cognitive and associative cortical areas, as supported by either tract-tracing techniques (Kelly & Strick, 2003; Middleton & Strick, 1994; Schmahmann & Caplan, 2006; Schmahmann & Pandya, 1995; Strick, Dum, & Fiez, 2009a) or diffusion MRI tractography studies of the cerebro-cerebellar loop (Kim, Im, Kim, & Park, 2019; Palesi et al, 2015, 2016, 2017)
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