The subthalamic nucleus (STN) is a small bi-convex structure situated in the diencephalon. Also known as the corpus Luysii, it was first described by French neurologist Jules Bernard Luys in 1865 (Luys, 1865
). A critical region in the regulation of normal movement, it is also involved in limbic and associative processing (Karachi et al., 2005
). The STN is a common surgical target when performing deep brain stimulation (DBS) for the symptoms of Parkinson's disease (Limousin et al., 1998
). More recently it has also been proposed as a target to modulate neuropsychiatric disorders such as obsessive-compulsive disorder (OCD) (Mallet et al., 2008
) and Tourette's syndrome (Martinez-Torres et al., 2009
Located at the diencephalo-mesencephalic junction, the borders of the STN are defined by the zona incerta superiorly and postero-medially; prelemniscal radiations and postero-lateral hypothalamus anteromedially and cerebral peduncle laterally. On its inferior-most lateral surface, lies the superior aspect of the substantia nigra pars reticulata. The inferior tip lies level with the mid-point of the red nucleus (RN), the superior tip lies at the level of the posterior commissure (Naidich et al., 2009
). Each nucleus is between 120 mm3
and 175 mm3
in volume (Hardman et al., 1997, 2002; Lévesque and Parent, 2005
), with the majority appearing hypointense on T2*-weighted images due to the presence of iron containing neuromelanin (Dormont et al., 2004; Tribl et al., 2009; Zecca et al., 2003
). It lies in a densely populated well vascularised region, and is the only excitatory glutamatergic nucleus within the basal ganglia network, projecting fibres to numerous targets (Marani et al., 2008
); principally the internal pallidum, putamen, substantia nigra and thalamus. Direct cortical connections from and to the STN exist, forming the basis for the hyperdirect pathway in motor processing (Nambu et al., 1997, 2002
Primate studies have demonstrated three functional zones within the STN: limbic, associative and sensorimotor regions residing in the anterior, mid and posterior STN respectively (Joel and Weiner, 1997; Karachi et al., 2005; Parent and Hazrati, 1995
). However, these functional subdivisions of the STN have not been conclusively demonstrated in humans.
Diffusion weighted imaging (DWI) is a magnetic resonance imaging (MRI) technique that allows analysis of white matter integrity in vivo (Pierpaoli and Basser, 1996
). Using probabilistic tractography, spatial distributions of white matter fibres (i.e. connectivity profiles) can be estimated for a single voxel (Behrens et al., 2003
). These estimated white matter fibre pathways have been previously validated in histological studies and correspond with known anatomy (Dyrby et al., 2007
). These connectivity profiles have been previously used to achieve accurate segmentation of regions not otherwise visible using conventional MRI techniques, for example the pre-motor cortices (Klein et al., 2007
). The objective of this study was to explore STN connectivity and segmentation in a bottom-up, prior free fashion by proceeding stepwise through the following aims:
1. Define the normal connectivity profile within the subthalamic nucleus of healthy controls to cortical and subcortical targets.
2. Use the diffusion tractography (DT) data to estimate the number of sub-clusters within the STN.
3. Using a clustering algorithm and calculated cluster number, segment the STN into distinct regions based on the connectivity profiles.
4. Examine how cortical and sub-cortical connectivity corresponds to the calculated sub-clusters.
5. To define functional zones based on the sub-regional connectivity patterns compared to pre-existing literature.