Do we need to revise the tripartite subdivision hypothesis of the human subthalamic nucleus (STN)? Response to Alkemade and Forstmann

The exciting development of ultra-high resolution 7Tesla (T) magnetic resonance imaging (MRI) has made it possible to clearly visualize and delineate the subthalamic nucleus (STN). Ultra-high resolution MRI provides a first step in the ongoing improvement of imaging techniques rendering it likely that in the near future specific subareas of small brain nuclei such as the STN can be visualized. These developments can contribute to improve clinical imaging, allowing even more accurate targeting of the STN. This is interesting in view of putative limbic, associative, and sensomotoric subdivisions within the STN. The concept of anatomically distinct subdivisions is attractive, both from an anatomical as well as a clinical perspective. However, we argue that the current leading hypothesis of three STN subdivisions is based on low numbers of clinical observations and primate tracing studies. 7T imaging provides us with markers that could potentially help us to distinguish subdivisions, but our preliminary findings do not indicate the existence of subdivisions. In our opinion additional research is needed. As a consequence the tripartite hypothesis should therefore still be a topic of debate. In view of the possible clinical implications, we would like to raise the question whether anatomical evidence on the topological organization within the STN points towards delineated subdivisions, or an organization without strict anatomical boundaries or septa. The latter would require a revision of the current tripartite hypothesis of the human STN.