Connectivity-based segmentation of human amygdala nuclei using probabilistic tractography

The amygdala plays an important role in emotional and social functions, and amygdala dysfunction has been associated with multiple neuropsychiatric disorders, including autism, anxiety, and depression. Although the amygdala is composed of multiple anatomically and functionally distinct nuclei, typical structural magnetic resonance imaging (MRI) sequences are unable to discern them. Thus, functional MRI (fMRI) studies typically average the BOLD response over the entire structure, which reveals some aspects of amygdala function as a whole but does not distinguish the separate roles of specific nuclei in humans. We developed a method to segment the human amygdala into its four major nuclei using only diffusion-weighted imaging and connectivity patterns derived mainly from animal studies. We refer to this new method as Tractography-based Segmentation, or TractSeg. The segmentations derived from TractSeg were topographically similar to their corresponding amygdaloid nuclei, and were validated against a high-resolution scan in which the nucleic boundaries were visible. In addition, nuclei topography was consistent across subjects. TractSeg relies on short scan acquisitions and widely accessible software packages, making it attractive for use in healthy populations to explore normal amygdala nucleus function, as well as in clinical and pediatric populations. Finally, it paves the way for implementing this method in other anatomical regions which are also composed of functional subunits that are difficult to distinguish with standard structural MRI.PHS Grant DA023427Poitras Center for Affective Disorders ResearchNational Center for Research Resources (U.S.) (P41-RR14075)National Center for Research Resources (U.S.) (BIRN Morphometric Project BIRN002)National Center for Research Resources (U.S.) (U24 RR021382)National Institute for Biomedical Imaging and Bioengineering (U.S.) (R01EB006758)National Institute on Aging (AG022381)National Institute of Neurological Disorders and Stroke (U.S.) (R01 NS052585-01)National Institute of Neurological Disorders and Stroke (U.S.) (1R21NS072652-01)National Institutes of Health (U.S.) (Shared Instrumentation Grant 1S10RR023401)National Institutes of Health (U.S.) (Shared Instrumentation Grant 1S10RR019)National Institutes of Health (U.S.) (Shared Instrumentation 1S10RR023043