Confirmation of functional zones within the human subthalamic nucleus: Patterns of connectivity and sub-parcellation using diffusion weighted imaging

TLDR

The subthalamic nucleus is a small glutamatergic diencephalic structure essential for motor control and a key target for deep‑brain stimulation in Parkinson’s disease, yet the existence of three functional sub‑zones, demonstrated in animals, has not been conclusively shown in humans. Using diffusion‑weighted imaging, we identified and parcellated three connectivity‑based clusters within the human STN that correspond to limbic, associative, and motor regions, providing the first in‑vivo, non‑invasive anatomical subdivision with implications for DBS surgery.

Abstract

The subthalamic nucleus (STN) is a small, glutamatergic nucleus situated in the diencephalon. A critical component of normal motor function, it has become a key target for deep brain stimulation in the treatment of Parkinson's disease. Animal studies have demonstrated the existence of three functional sub-zones but these have never been shown conclusively in humans. In this work, a data driven method with diffusion weighted imaging demonstrated that three distinct clusters exist within the human STN based on brain connectivity profiles. The STN was successfully sub-parcellated into these regions, demonstrating good correspondence with that described in the animal literature. The local connectivity of each sub-region supported the hypothesis of bilateral limbic, associative and motor regions occupying the anterior, mid and posterior portions of the nucleus respectively. This study is the first to achieve in-vivo, non-invasive anatomical parcellation of the human STN into three anatomical zones within normal diagnostic scan times, which has important future implications for deep brain stimulation surgery.