Functional segmentation of the anterior limb of the internal capsule: Linking white matter abnormalities to specific connections

Ziad Safadi, Giorgia Grisot, Saad Jbabdi, Timothy E. Behrens, Sarah R. Heilbronner, Nicole C.R. McLaughlin, Joe Mandeville, Amelia Versace, Mary L. Phillips, Julia F. Lehman, Anastasia Yendiki, Suzanne N. Haber

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The anterior limb of the internal capsule (ALIC) carries thalamic and brainstem fibers from prefrontal cortical regions that are associated with different aspects of emotion, motivation, cognition processing, and decision-making. This large fiber bundle is abnormal in several psychiatric illnesses and a major target for deep brain stimulation. Yet, we have very little information about where specific prefrontal fibers travel within the bundle. Using a combination of tracing studies and diffusionMRIin malenonhumanprimates, as well as diffusion MRI in male and female human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions within the capsule. Fractional anisotropy (FA) abnormalities in patients with bipolar disorder were detected whenFAwas averaged in the ALIC segment that carries ventrolateral prefrontal cortical connections. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and demonstrate the utility of applying connectivity profiles of large white matter bundles based on animal anatomic studies to human connections and associating disease abnormalities in those pathways with specific connections. The ability to functionally segment large white matter bundles into their components begins a new era of refining how we think about white matter organization and use that information in understanding abnormalities.

Original languageEnglish (US)
Pages (from-to)2106-2117
Number of pages12
JournalJournal of Neuroscience
Issue number8
StatePublished - Feb 21 2018

Bibliographical note

Funding Information:
The anatomic tracing and animal imaging studies were supported by NIMH Grants MH045573 and MH106435. TheclinicalstudiesweresupportedbyNIMHGrantMH103931.ThediffusionMRIanimalstudieswereperformedin part using resources provided by the Center for Functional Neuroimaging Technologies (P41-EB015896) and in-

Funding Information:
volved the use of instrumentation supported by Shared Instrumentation Grants S10RR016811, S10RR023401, and S10RR019307. Data were provided in part by the MGH-USC Human Connectome Project (U01-MH093765), funded by the NIH Blueprint for Neuroscience Research. The authors declare no competing financial interests. CorrespondenceshouldbeaddressedtoSuzanneN.Haber,DepartmentofPharmacologyandPhysiology,Universityof RochesterMedicalCenter,601ElmwoodAvenue,Rochester, DOI:10.1523/JNEUROSCI.2335-17.2017 Copyright©2018theauthors 0270-6474/18/382106-12$15.00/0


  • Anatomic tracing
  • Bipolar disorder
  • Diffusion MRI
  • Prefrontal cortex
  • White matter

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