A Connectomic Analysis of the Human Basal Ganglia Network.

Alberto Cacciola,Demetrio Milardi,Enricomaria Mormina,Angelo Quartarone,Alessandro Calamuneri,Giuseppina Rizzo,Giuseppe Anastasi,Antonino Naro,Gaetana Chillemi,Silvia Marino

doi:10.3389/fnana.2017.00085

Alberto Cacciola, Demetrio Milardi + Show 8 more

Open Access

https://doi.org/10.3389/fnana.2017.00085

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Abstract

The current model of basal ganglia circuits has been introduced almost two decades ago and has settled the basis for our understanding of basal ganglia physiology and movement disorders. Although many questions are yet to be answered, several efforts have been recently made to shed new light on basal ganglia function. The traditional concept of “direct” and “indirect” pathways, obtained from axonal tracing studies in non-human primates and post-mortem fiber dissection in the human brain, still retains a remarkable appeal but is somehow obsolete. Therefore, a better comprehension of human structural basal ganglia connectivity in vivo, in humans, is of uttermost importance given the involvement of these deep brain structures in many motor and non-motor functions as well as in the pathophysiology of several movement disorders. By using diffusion magnetic resonance imaging and tractography, we have recently challenged the traditional model of basal ganglia network by showing the possible existence, in the human brain, of cortico-pallidal, cortico-nigral projections, which could be mono- or polysynaptic, and an extensive subcortical network connecting the cerebellum and basal ganglia. Herein, we aimed at reconstructing the basal ganglia connectome providing a quantitative connectivity analysis of the reconstructed pathways. The present findings reinforce the idea of an intricate, not yet unraveled, network involving the cerebral cortex, basal ganglia, and cerebellum. Our findings may pave the way for a more comprehensive and holistic pathophysiological model of basal ganglia circuits.

Highlights

The current view of basal ganglia neurophysiology is largely based on data from rodents and nonhuman primates using various tract-tracing methods for the study of monosynaptic connections combined with immunohistochemistry and in situ hybridization (Albin et al, 1989; DeLong, 1990)
We performed a connectivity analysis on diffusion MRI data in order to characterize the topographical distribution of the connections involved in the cortico-basal ganglia-cerebellar network
Besides confirming the dense striatal and subthalamic structural connectivity with several frontal and parietal areas, we here showed that the GP and substantia nigra (SN) are densely interconnected with the cerebral cortex as well

Summary

Introduction

The current view of basal ganglia neurophysiology is largely based on data from rodents and nonhuman primates using various tract-tracing methods for the study of monosynaptic connections combined with immunohistochemistry and in situ hybridization (Albin et al, 1989; DeLong, 1990). According to this view, the cerebral cortex is widely connected with the basal ganglia via two major projection systems; the so-called “direct” and “indirect” striatofugal pathways originating from segregated populations of striatal projection neurons that exert opposite effects upon basal ganglia outflow. In the last 20 years, Diffusion Tensor Imaging (DTI) tractography has been used as an anatomical “virtual dissector” for tracking in vivo and non-invasively neural connectivity in the human brain (Basser et al, 1994; Henderson, 2012; Nunnari et al, 2014), by measuring anisotropy diffusion of water molecules (Mori and Van Zijl, 2002)

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