The ansa subthalamica: a neglected fiber tract

Background The pallidofugal pathways are classically subdivided into ansa lenticularis, lenticular fasciculus, and subthalamic fasciculus. In addition to these three subsystems, we characterize an anatomical structure that connects the antero-medial pole of the subthalamic nucleus to the ventral portions of the pallidum, both related to limbic processing of information. This bundle has been previously considered to form a part of the ansa lenticularis, however, it shows striking differences on histology and MRI features compared to the ansa lenticularis, and therefore we suggest to denominate it ansa subthalamica . Objectives To describe the ansa subthalamica as a different structure than the ansa lenticularis, that can be recognized by different methods (histology, high-field MRI and connectome tractography), including current 3T clinical imaging. Methods A complete human brain was histologically processed and submitted to registration procedures to correct for tissue deformations and normalization to MNI space. Coordinates of histological structures were then comparable to high-field (7T) post-mortem and in vivo MRIs, 13 pre-operative 3T imaging of parkinsonian patients and normative connectome tractography. Mean intensity gray values for different structures were measured in Susceptibility-Weighted Images. Results It was possible to characterize this structure with different methods and there was significant difference in signal intensity in the ansa subthalamica (hypointense), compared to the ansa lenticularis (hyperintense). Conclusions The ansa subhtalamica may represent the anatomical pathway that connects limbic regions of the STN and pallidum, and should be investigated as a possible substrate for limbic effects of stereotactic surgery of the subthalamic region. ### Competing Interest Statement The author Bruce Fischl (BF) has a financial interest in CorticoMetrics, a company whose medical pursuits focus on brain imaging and measurement technologies. BF's interests were reviewed and are managed by Massachusetts General Hospital and Partners HealthCare in accordance with their conflict of interest policies. The remaining authors disclose any actual or potential conflict of interest including any financial, personal or other relationships with people or organizations within 3 years of beginning the submitted work that could inappropriately influence, or be perceived to influence their work. ### Clinical Trial Not a clinical trial ### Funding Statement Support for this research was provided in part by the BRAIN Initiative Cell Census Network grant U01MH117023, the National Institute for Biomedical Imaging and Bioengineering (P41EB015896, 1R01EB023281, R01EB006758, R21EB018907, R01EB019956), the National Institute on Aging (5R01AG008122, R01AG016495), the National Institute for Neurological Disorders and Stroke (R01NS0525851, R21NS072652, R01NS070963, R01NS083534, 5U01NS086625), and was made possible by the resources provided by Shared Instrumentation Grants 1S10RR023401, 1S10RR019307, and 1S10RR023043. Additional support was provided by the NIH Blueprint for Neuroscience Research (5U01-MH093765), part of the multi-institutional Human Connectome Project. Resources from Universities of S?o Paulo and W?rzburg supported part of the research. The author Eduardo Joaquim Lopes Alho was supported by a scholarship from CAPES (Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior) agency, Brazil, for doctoral studies at the University of W?rzburg, Germany. ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes Any clinical trials involved have been registered with an ICMJE-approved registry such as ClinicalTrials.gov and the trial ID is included in the manuscript. Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Not Applicable Data are available upon reasonable request * AL : ansa lenticularis AS : ansa subthalamica DBS : Deep brain stimulation GPe : globus pallidus externus GPi : globus pallidus internus IC : Internal capsule SF : subthalamic fasciculus STN : subthalamic nucleus LF : lenticular fasciculus