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J Neurosci. 2018 Feb 21;38(8):2106-2117. doi: 10.1523/JNEUROSCI.2335-17.2017. Epub 2018 Jan 22.

Functional Segmentation of the Anterior Limb of the Internal Capsule: Linking White Matter Abnormalities to Specific Connections.

Author information

1
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
2
Athinoula A. Martinos Center for Biomedical Imaging, Harvard University and Massachusetts General Hospital, Boston, Massachusetts 02129.
3
Harvard-MIT Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
4
Wellcome Centre for Integrative Neuroimaging, Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, United Kingdom.
5
Wellcome Centre for Neuroimaging, Institute of Neurology, University College London, London WC1N 3BG, United Kingdom.
6
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, and.
7
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, suzanne_haber@urmc.rochester.edu.
8
Department of Psychiatry, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478.

Abstract

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 diffusion MRI in male nonhuman primates, 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 when FA was 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.SIGNIFICANCE STATEMENT The anterior limb of the internal capsule (ALIC) connects prefrontal cortex with the thalamus and brainstem and is abnormal in psychiatric illnesses. However, we know little about the location of specific prefrontal fibers within the bundle. Using a combination of animal tracing studies and diffusion MRI in animals and human subjects, we segmented the human ALIC into five regions based on the positions of axons from different cortical regions. We then demonstrated that differences in FA values between bipolar disorder patients and healthy control subjects were specific to a given segment. Together, the results set the stage for linking abnormalities within the ALIC to specific connections and for refining how we think about white matter organization in general.

KEYWORDS:

anatomic tracing; bipolar disorder; diffusion MRI; prefrontal cortex; white matter

PMID:
29358360
PMCID:
PMC5824744
DOI:
10.1523/JNEUROSCI.2335-17.2017
[Indexed for MEDLINE]
Free PMC Article

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