» See the corresponding retraction notice, DOI: 10.3171/2015.10.JNS145r, for full details. « LABORATORY INVESTIGATION Anatomy of the subthalamic nucleus, with correlation of deep brain stimulation Akın Akakın, MD,1 Baran Yılmaz, MD,1 Türker Kılıç, MD,1 PhD, and Albert L. Rhoton Jr., MD2 1Department of Neurosurgery, School of Medicine, Bahcesehir University, Istanbul, Turkey; and 2Department of Neurosurgery, School of Medicine, University of Florida, Gainesville, Florida O BJECT The goal in this study was to examine the cadaveric anatomy of the subthalamic nucleus (STN) and to analyze the implications of the findings for deep brain stimulation (DBS) surgery. METHODS Five formalin-fixed human cerebrums were dissected using the Klingler fiber dissection technique. Digital photographs of the dissections were fused to obtain an anaglyphic image. RESULTS The STN was located posteroinferior to the anterior corticospinal fibers, posterosuperior to the substantia nigra, and anteromedial to the red nucleus, lenticular fasciculus, and thalamic fasciculus. The subthalamic region is ven- tral to the thalamus, medial to the internal capsule, and lateral and caudal to the hypothalamus. The nuclei found within the subthalamic region include the STN. The relationship between the STN and surrounding structures, which are not delineated sharply, is described. CONCLUSIONS The fiber dissection technique supports the presence of the subthalamic region as an integrative net- work in humans and offers the potential to aid in understanding the impacts of DBS surgery of the STN in patients with Parkinson disease. Further research is needed to define the exact role of the STN in the integrative process. http://thejns.org/doi/abs/10.3171/2014.10.JNS145 KEY WORDS neuroanatomy; subthalamic nucleus; fiber dissection; anatomy HE subthalamic nucleus (STN) is an important part of the STN and movement. In this study we describe the of the brain related to Parkinson disease (PD) and anatomical relationship between the STN and surrounding other involuntary movements. The STN contains structures. Tsome fibers that travel to the cortical area and basal gan- glia.2 The STN is located just superomedial to the red Methods nucleus and substantia nigra. Widely acknowledged as an important modulator of basal ganglia output, the STN re- Anatomical Study ceives its major afferents from the cerebral cortex, thala- The cerebral hemispheres and cerebrums of 5 human mus, globus pallidus externus (GPe), and brainstem. The cadavers were fixed in a 10% formalin solution for at least STN projects mainly to both segments of the GP, sub- 3 weeks. The first step in the preparation of the specimens stantia nigra, striatum, and brainstem and is essentially was the removal of the arachnoidal and vascular structures composed of glutamatergic neurons. Lesions of the STN with the aid of a surgical microscope (magnification range induce choreiform abnormal movements and ballism on ×6 to ×40). The hemispheres were frozen at -16°C for 2–4 the contralateral side of the body.2,3 Despite current inter- weeks. Twenty-four hours after completion of the freezing est, little is knownRetracted about the relation between function process, the white fiber dissection was done with fine and ABBREVIATIONS DBS = deep brain stimulation; GPe, GPi = globus pallidus externus, globus pallidus internus; PD = Parkinson disease; STN = subthalamic nucleus. SUBMITTED January 16, 2014. ACCEPTED October 15, 2014. INCLUDE WHEN CITING Published online April 24, 2015; DOI: 10.3171/2014.10.JNS145. DISCLOSURE The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper. ©AANS, 2015 J Neurosurg April 24, 2015 1 A. Akakın et al. self-shaped wooden spatulas. We took numerous digital tween the claustrum and the putamen. By removing the photographs during dissections and, using a specific soft- fibers of the dorsal extreme capsule, we can see the fibers ware program (Anamaker 3D; available free from www. of the dorsal external capsule at the periphery of the dorsal stereoeye.com), we fused the images to obtain an ana- claustrum. At the level of the limen insula, the uncinate glyphic image. fasciculus and inferior frontooccipital fasciculus can be observed (Fig. 1). Results After dissection of the crus cerebri, we first observe the Anatomical Dissection substantia nigra, which is located superolateral to the red nucleus. When the red nucleus is dissected, fibers of the The dissection of the brain is started from the gray mat- ansa lenticularis can be observed. The STN is located pos- ter of the cortex, and U-fibers are observed under the gray teroinferior to the anterior corticospinal fibers, posterosu- matter. After the removal of U-fibers, the cortical fibers perior to the substantia nigra, and anteromedial to the red are seen. To expose the superior longitudinal fasciculus, nucleus, lenticular fasciculus, and thalamic fasciculus. The we remove the cortical gray matter; adjacent superficial STN had a café-au-lait color in cadaver sections (Fig. 2). short fibers of the frontal, temporal, and parietal oper- cula; the middle, frontal, superior, and middle temporal Identification of the STN gyri; and the inferior parietal lobule. The first identified fasciculus in dissection, which begins on the lateral hemi- The STN is a small, lens-shaped nucleus in the brain. spheric surface, is the superior longitudinal (arcuate) fas- The STN is a part of the basal ganglia system and is lo- ciculus. Traditionally, this fasciculus can be described as cated ventral to the thalamus, dorsal to the substantia nig- a reversed C-shaped structure, which surrounds the insula ra, and medial to the internal capsule (Fig. 3). Anterior and interconnects the frontal and temporal lobes (Fig. 1). and lateral borders of the STN are enveloped by fibers of At a deeper level in the temporoparietal area, a group the internal capsule, which separates this nucleus laterally of fibers arching around the posterosuperior insular bor- from the GP. Posteromedially, the STN is very close to der is seen to be traveling between the posterior temporal the red nucleus. The ventral borders of the STN are the region and the prefrontal area. These fibers form the fron- cerebral peduncle and the substantia nigra. Dorsally, the totemporal or arcuate segment of the superior longitudi- STN has a border with the fasciculus lenticularis, which nal fasciculus. By dissecting the inferolateral hemispheric separates the STN from the ventral thalamus. surface, we can see a group of fibers deep to the tempo- Several fiber tracts course near the borders of the STN. roparietal segment of the superior longitudinal fasciculus The subthalamic fasciculus consists of fibers that inter- (Fig. 1). connect the STN and GP. This fiber bundle arises from Progressive dissection of the fibers of the superior lon- the inferolateral border of the STN (Fig. 2). gitudinal fasciculus reveals the insular cortex. After re- The ansa lenticularis consists of fibers from the globus moval of the insular subcortex, we can see the white fibers pallidus internus (GPi) that project toward the thalamus. of the extreme capsule; and at the level of the limen in- It originates mainly from the lateral portion of the GPi, sula, the fibers of the uncinate and inferior occipitofrontal coursing in a medial, ventral, and rostral direction and fascicles can be distinguished. The extreme capsule is a sweeping anteriorly around the posterior limb of the in- group of fibers situated between the insular cortex and the ternal capsule. This tract arises from the medial aspect claustrum (Fig. 1). of the GPi, perforates the internal capsule, and forms a The external capsule is composed of fibers situated be- bundle ventral to the zona incerta. Although some fibers FIG. 1. A: Gray matter has been dissected, and fibers have been uncovered. The gyri and sulci have been identified. B: Fibers haveRetracted been dissected; the claustrum can be seen. Internal capsules have been dissected. The inferior frontal fasciculus and uncinate fasciculus are identified. The optic radiation can be followed inferiorly. C: The claustrum has been dissected, and the putamen is identified. The sagittal stratum can be followed, radiating posteriorly. Fasc. = fasciculus; Front. = frontal; gyr. = gyrus; i.c. = internal capsule; Inf. = inferior; Int. = internal; Lat. Gen. bod = lateral geniculate body; long. = longitudinal; Midd. = middle; Occ. = occipital; rad. = radiation; Sup. = superior; Temp. = temporal. Figure is available in color online only. 2 J Neurosurg April 24, 2015 Subthalamic nucleus anatomy FIG. 2. Left: View from the medial aspect of the cerebrum. The red nucleus can be viewed medial to the substantia nigra. The thalamus is located posterolateral to the substantia nigra. The optic nerve and the stalk can be observed medially. Right: Subtha- lamic nucleus and ansa lenticularis fibers are seen. Association fibers between basal ganglia and the STN can be viewed. The red nucleus is located medially and inferiorly. The ansa lenticularis and substantia nigra can be seen on the inferior and lateral side of the STN, respectively. Pit. = pituitary. Figure is available in color online only. from the lenticular fasciculus are dorsal to the STN, most nuclei found within the subthalamic region include the of this tract courses rostral to the nucleus. Fiber tracts ly- STN and zona incerta. The STN has a very close relation- ing posterior to the STN include the medial lemniscus, ship with the substantia nigra and the red nucleus (Fig. 5). spinothalamic tract, and trigeminothalamic tract (Fig. 2). In particular, the dorsal aspects of the lateral portion of Discussion the rostral two-thirds and the caudal one-third of the nu- cleus are anatomically related to the motor circuits. Sub- The STN is a small, lens-shaped nucleus in the brain. thalamic afferent fibers, corticosubthalamic projections, The STN is part of the basal ganglia system and is located and most of the cortical afferents to the STN arise from ventral to the thalamus, dorsal to the substantia nigra, and the primary motor cortex, supplementary motor area, pre– medial to the internal capsule.