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bioRxiv · 10.1101/178533

Intrinsic functional connectivity of the central extended amygdala

Tillman, R. M.·Stockbridge, M. D.·Nacewicz, B. M.·Torrisi, S.·Fox, A. S.·Smith, J. F.·Shackman, A. J.
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Abstract

The central extended amygdala (EAc)--including the bed nucleus of the stria terminalis (BST) and central nucleus of the amygdala (Ce)--plays a key role in orchestrating states of fear and anxiety and is implicated in the development and maintenance of anxiety disorders, depression, and substance abuse. Although it is widely thought that these disorders reflect the coordinated actions of large-scale functional circuits in the brain, the architecture of the EAc functional network, and the degree to which the BST and the Ce show distinct patterns of intrinsic functional connectivity, remains incompletely understood. Here, we leveraged a combination of approaches to trace the connectivity of the BST and the Ce in 130 psychiatrically healthy, racially diverse, community-dwelling adults with enhanced power and precision. Multiband imaging, high-precision data registration techniques, and spatially unsmoothed data were used to maximize anatomical specificity. Using newly developed seed regions, whole-brain regression analyses revealed robust functional connectivity between the BST and Ce via the sublenticular extended amygdala ( substantia innominata), the ribbon of subcortical gray matter encompassing the ventral amygdalofugal pathway. Both regions displayed significant coupling with the ventromedial prefrontal cortex (vmPFC), midcingulate cortex (MCC), insula, and anterior hippocampus. The BST showed significantly stronger connectivity with prefrontal territories--including the vmPFC, anterior MCC and pregenual anterior cingulate cortex--as well as the thalamus, striatum, and the periaqueductal gray. The only regions showing stronger functional connectivity with the Ce were located in the anterior hippocampus and dorsal amygdala. These observations provide a baseline against which to compare a range of special populations, inform our understanding of the role of the EAc in normal and pathological fear and anxiety, and highlight the value of several new approaches to image registration which may be particularly useful for researchers working with de-identified neuroimaging data.\n\nGRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC=\"FIGDIR/small/178533_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (61K):\norg.highwire.dtl.DTLVardef@10ce93corg.highwire.dtl.DTLVardef@a467ceorg.highwire.dtl.DTLVardef@19b4550org.highwire.dtl.DTLVardef@e38e2a_HPS_FORMAT_FIGEXP M_FIG Intrinsic functional connectivity of bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (Ce) in 130 psychiatrically healthy adults.\n\nC_FIG HIGHLIGHTSO_LIBST and Ce implicated in normal and pathological fear and anxiety\nC_LIO_LITraced the intrinsic functional connectivity of the BST and the Ce in 130 adults\nC_LIO_LIMultiband imaging, high-precision registration, unsmoothed data, newly developed seeds\nC_LIO_LIBST and Ce show robust coupling with one another, hippocampus, insula, MCC, and vmPFC\nC_LIO_LIBST shows stronger coupling with prefrontal/cingulate territories and brainstem/PAG\nC_LI

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Tillman, R. M., Stockbridge, M. D., Nacewicz, B. M., Torrisi, S., Fox, A. S., Smith, J. F., Shackman, A. J.. 2017-08-20. Intrinsic functional connectivity of the central extended amygdala. https://doi.org/10.1101/178533

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