Abstract
The zona incerta (ZI) is a small gray matter region of the deep brain first identified in the 19th century, yet direct in vivo visualization and characterization has remained elusive. Noninvasive detection of the ZI and surrounding region could be critical to further our understanding of this widely connected but poorly understood deep brain region and could contribute to the development and optimization of neuromodulatory therapies. We demonstrate that high resolution (submillimetric) longitudinal (T1) relaxometry measurements at high magnetic field strength (7 T) can be used to delineate the ZI from surrounding white matter structures, specifically the fasciculus cerebellothalamicus, fields of Forel (fasciculus lenticularis, fasciculus thalamicus, and field H), and medial lemniscus. Using this approach, we successfully derived in vivo estimates of the size, shape, location, and tissue characteristics of substructures in the ZI region, confirming observations only previously possible through histological evaluation that this region is not just a space between structures but contains distinct morphological entities that should be considered separately. Our findings pave the way for increasingly detailed in vivo study and provide a structural foundation for precise functional and neuromodulatory investigation.
Highlights
The zona incerta (ZI) is a small but diffuse structure in the deep brain first identified by Auguste Forel in 1877, famously described as “an immensely confusing area about which nothing can be said” (Forel, 1877)
We report that, by employing highresolution longitudinal (T1) mapping at 7 T, robust visualization of the ZI and surrounding WM structures is possible in vivo along the entire rostrocaudal axis, allowing comprehensive anatomical characterization of this previously obscure deep brain region
We found that the human ZI could be directly visualized in vivo along its entire rostrocaudal axis as a region of high T1 signal
Summary
The zona incerta (ZI) is a small but diffuse structure in the deep brain first identified by Auguste Forel in 1877, famously described as “an immensely confusing area about which nothing can be said” (Forel, 1877). Forel appreciated that the ZI consisted of gray matter located between the external medullary lamina of the thalamus and the corpus Luysi (subthalamic nucleus; STN) of otherwise “indefinite” description. It is telling that Forel found the ZI so difficult to describe given his crucial role in the delineation of surrounding white matter tracts still referred to eponymously as the fields of Forel (Gallay, Jeanmonod, Liu, & Morel, 2008). Packed in a small area between the ventral thalamus, STN, and red nucleus (RN), the ZI is situated at a complex junction of major white matter pathways including the cerebellothalamic, pallidothalamic, medial lemniscal, and corticospinal tracts. Most of the details regarding the region are the result of meticulous study of postmortem specimens (Gallay et al, 2008; Morel, 2007; Schaltenbrand & Wahren, 1977)
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