Structural and Resting State Functional Connectivity of the Subthalamic Nucleus: Identification of Motor STN Parts and the Hyperdirect Pathway

Abstract

Deep brain stimulation (DBS) for Parkinson’s disease often alleviates the motor symptoms, but causes cognitive and emotional side effects in a substantial number of cases. Identification of the motor part of the subthalamic nucleus (STN) as part of the presurgical workup could minimize these adverse effects. In this study, we assessed the STN’s connectivity to motor, associative, and limbic brain areas, based on structural and functional connectivity analysis of volunteer data. For the structural connectivity, we used streamline counts derived from HARDI fiber tracking. The resulting tracks supported the existence of the so-called “hyperdirect” pathway in humans. Furthermore, we determined the connectivity of each STN voxel with the motor cortical areas. Functional connectivity was calculated based on functional MRI, as the correlation of the signal within a given brain voxel with the signal in the STN. Also, the signal per STN voxel was explained in terms of the correlation with motor or limbic brain seed ROI areas. Both right and left STN ROIs appeared to be structurally and functionally connected to brain areas that are part of the motor, associative, and limbic circuit. Furthermore, this study enabled us to assess the level of segregation of the STN motor part, which is relevant for the planning of STN DBS procedures.

Individualized parcellation of the subthalamic nucleus in patients with Parkinson's disease with 7T MRI

“…The averaged locations of these zones in healthy subjects correspond with our findings in individual patients. This arrangement was also observed in another 3 T functional and structural connectivity study based on averaged data of healthy subjects, but could not be demonstrated consistently in all individual subjects (Brunenberg et al, 2012). Finally the STN’s connectivity was previously investigated in PD patients as well, although this only concerned its motor area and analyses were only performed in a qualitative manner (Avecillas-Chasin et al, 2015).…”

Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus

“…A once widely held assumption is that the STN is divided into three functional zones within the STN: limbic, associative, and sensorimotor regions, residing in the anteromedial, middle, and dorsolateral portions, respectively, of the STN (58,68,69). This concept has been challenged by several recent electrophysiologic, neuroanatomic, and neuroimaging studies showing incomplete separation of the subthalamic territories (56,63,70,71). Therefore, it is not surprising that the affective neurons were found in the sensorimotor regions, suggesting that motor and nonmotor regions overlap in the STN.…”

Neuroimaging of Parkinson's disease: Expanding views

“…Figure 6 shows white matter pathways that have been imaged only recently for the first time in vivo in humans using DTI. These include the nigrostriatal, nigrothalamic, pallidothalamic, subthalamopallidal, striatopallidal (Lenglet et al, 2012), and hyperdirect pathways (Brunenberg et al, 2012) in normal subjects; and cerebellar subthalamopontocerebellar and dentatothalamic tracts in PD patients (Sweet et al, 2014). …”

“…Bold: neuroimaging of structural connections in humans in vivo by Brunenberg et al (2012; hyperdirect pathway), Sweet et al (2014; subthalamopontocerebellar and dentothalamic tracts), and Lenglet et al (2012; other bold pathways).…”