Abstract

The basal ganglia is part of a complex system of neuronal circuits that play a key role in the integration and execution of motor, cognitive and emotional function in the human brain. Parkinson’s disease is a progressive neurological disorder of the motor circuit characterized by tremor, rigidity, and slowness of movement. Deep brain stimulation (DBS) of the subthalamic nucleus and the globus pallidus pars interna provides an efficient treatment to reduce symptoms and levodopa-induced side effects in Parkinson’s disease patients. While the underlying mechanism of action of DBS is still unknown, the potential modulation of white matter tracts connecting the surgical targets has become an active area of research. With the introduction of advanced diffusion MRI acquisition sequences and sophisticated post-processing techniques, the architecture of the human brain white matter can be explored in vivo. The goal of this study is to investigate the white matter connectivity between the subthalamic nucleus and the globus pallidus. Two multi-fiber tractography methods were used to reconstruct pallido-subthalamic, subthalamo-pallidal and pyramidal fibers in five healthy subjects datasets of the Human Connectome Project. The anatomical accuracy of the tracts was assessed by four judges with expertise in neuroanatomy, functional neurosurgery, and diffusion MRI. The variability among subjects was evaluated based on the fractional anisotropy and mean diffusivity of the tracts. Both multi-fiber approaches enabled the detection of complex fiber architecture in the basal ganglia. The qualitative evaluation by experts showed that the identified tracts were in agreement with the expected anatomy. Tract-derived measurements demonstrated relatively low variability among subjects. False-negative tracts demonstrated the current limitations of both methods for clinical decision-making. Multi-fiber tractography methods combined with state-of-the-art diffusion MRI data have the potential to help identify white matter tracts connecting DBS targets in functional neurosurgery intervention.

Highlights

  • Deep brain stimulation (DBS) is an efficient neurosurgical treatment to alleviate motor symptoms, levodopa-induced motor fluctuations, and dyskinesia in Parkinson’s disease patients (Benabid et al, 1987; Krack and Hariz, 2013)

  • The introduction of diffusion Magnetic resonance imaging (MRI) and subsequent development of tractography techniques have opened up the possibility to map the architecture of the Abbreviations: DBS, deep brain stimulation; dMRI, diffusion MRI; GP, globus pallidus; GPe, globus pallidus pars externa; GPi, globus pallidus pars interna; HCP, Human Connectome Project; MC, multi-compartment; MSMT-CSD, multi-shell multi-tissue constrained spherical deconvolution; PD, Parkinson’s disease; ROI, region of interest; STN, subthalamic nucleus

  • We propose to investigate the connectivity between the subthalamic nucleus and the globus pallidus using two multi-fiber tractography approaches on five HCP subjects

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Summary

Introduction

Deep brain stimulation (DBS) is an efficient neurosurgical treatment to alleviate motor symptoms, levodopa-induced motor fluctuations, and dyskinesia in Parkinson’s disease patients (Benabid et al, 1987; Krack and Hariz, 2013). The subthalamic nucleus (STN) and globus pallidus pars interna (GPi) have been established as effective targets (Wagle Shukla and Okun, 2014; Fasano and Lozano, 2015) Both nuclei are components of a large segregated cortical-subcortical network and DBS is likely to activate white matter fiber tracts connecting the targeted regions (Ashby et al, 1999; Gradinaru et al, 2009). Experimental studies in monkeys have demonstrated the subdivision of the basal ganglia into three functional motor, limbic and associative territories arising from the cerebral cortex (Haber et al, 1993; François et al, 1994; Karachi et al, 2005; Haynes and Haber, 2013). The introduction of diffusion MRI (dMRI) and subsequent development of tractography techniques have opened up the possibility to map the architecture of the Abbreviations: DBS, deep brain stimulation; dMRI, diffusion MRI; GP, globus pallidus; GPe, globus pallidus pars externa; GPi, globus pallidus pars interna; HCP, Human Connectome Project; MC, multi-compartment; MSMT-CSD, multi-shell multi-tissue constrained spherical deconvolution; PD, Parkinson’s disease; ROI, region of interest; STN, subthalamic nucleus

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