Topographic organization of the human and non-human primate subthalamic nucleus.

Alfons Schnitzler,Anneke Alkemade,Birte U. Forstmann

doi:10.1007/s00429-015-1047-2

Alfons Schnitzler, Anneke Alkemade + Show 1 more

Open Access

https://doi.org/10.1007/s00429-015-1047-2

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Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is used to relieve motor symptoms of Parkinson’s disease. A tripartite system of STN subdivisions serving motoric, associative, and limbic functions was proposed, mainly based on tracing studies, which are limited by low numbers of observations. The evidence is compelling and raises the question as to what extent these functional zones are anatomically segregated. The majority of studies indicate that there is anatomical overlap between STN functional zones. Using ultrahigh-resolution magnetic resonance imaging techniques it is now possible to visualize the STN with high spatial resolution, and it is feasible that in the near future stereotactic guided placement of electrical stimulators aided by high-resolution imaging will allow for more specific stimulation of the STN. The neuroanatomical and functional makeup of these subdivisions and their level of overlap would benefit from clarification before serving as surgical targets. We discuss histological and imaging studies, as well as clinical observations and electrophysiological recordings in DBS patients. These studies provide evidence for a topographical organization within the STN, although it remains unclear to what extent functionally and anatomically distinct subdivisions overlap.

Highlights

The subthalamic nucleus (STN) lies deep within the brain on top of the cerebral peduncle and plays a central role in both the direct and indirect pathway of the basal ganglia (Temel et al 2005) (Fig. 1)
Studies point toward topographical organization without clear borders in the STN (Haynes and Haber 2013; Alkemade 2013) (Fig. 2)
A second study corroborated the absence of dopamine 1 receptor (D1R) from the STN; this study reported a lack of D2R hybridization signal from the STN (Augood et al 2000)

Summary

Introduction

The subthalamic nucleus (STN) lies deep within the brain on top of the cerebral peduncle and plays a central role in both the direct and indirect pathway of the basal ganglia (Temel et al 2005) (Fig. 1). Low level of anatomical detail Low level of anatomical detail Low level of anatomical detail, usually low number of observations, not always normal brain function rodent studies, but in the present review we will focus on data obtained in primates We made this choice, since to a large extent human and rodent data are comparable, there may be small anatomical differences present between subdivisions in distinct species. Based on tracing studies using a variety of different tracers several groups have provided evidence for the existence of 0–4 anatomofunctional subdivisions within the STN (Alexander and Crutcher 1990; Parent and Hazrati 1995a, b; Joel and Weiner 1997; Keuken et al 2012; Haynes and Haber 2013). Unintentional targeting of the limbic and associative parts of the STN has been hypothesized to cause limbic-behavioral side effects (Mallet et al 2007)

Conclusions tracing studies

Conclusions cytoarchitectural studies

Conclusions in vivo imaging

Conclusions clinical observations

Conclusions electrophysiological recordings in DBS patients

Concluding remarks