Journal article
Pharmacological Modulation of Noradrenergic Arousal Circuitry Disrupts Functional Connectivity of the Locus Ceruleus in Humans
The Journal of neuroscience, v 37(29), pp 6938-6945
19 Jul 2017
PMID: 28626012
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
State-dependent activity of locus ceruleus (LC) neurons has long suggested a role for noradrenergic modulation of arousal. However, in vivo insights into noradrenergic arousal circuitry have been constrained by the fundamental inaccessibility of the human brain for invasive studies. Functional magnetic resonance imaging ( fMRI) studies performed during site-specific pharmacological manipulations of arousal levels may be used to study brain arousal circuitry. Dexmedetomidine is an anesthetic that alters the level of arousal by selectively targeting alpha 2 adrenergic receptors on LC neurons, resulting in reduced firing rate and norepinephrine release. Thus, we hypothesized that dexmedetomidine-induced altered arousal would manifest with reduced functional connectivity between the LC and key brain regions involved in the regulation of arousal. To test this hypothesis, we acquired resting-state fMRI data in right-handed healthy volunteers 18-36 years of age (n = 15, 6 males) at baseline, during dexmedetomidine-induced altered arousal, and recovery states. As previously reported, seed-based resting-state fMRI analyses revealed that the LC was functionally connected to a broad network of regions including the reticular formation, basal ganglia, thalamus, posterior cingulate cortex (PCC), precuneus, and cerebellum. Functional connectivity of the LC to only a subset of these regions ( PCC, thalamus, and caudate nucleus) covaried with the level of arousal. Functional connectivity of the PCC to the ventral tegmental area/pontine reticular formation and thalamus, in addition to the LC, also covaried with the level of arousal. We propose a framework in which the LC, PCC, thalamus, and basal ganglia comprise a functional arousal circuitry.
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Details
- Title
- Pharmacological Modulation of Noradrenergic Arousal Circuitry Disrupts Functional Connectivity of the Locus Ceruleus in Humans
- Creators
- Andrew H. Song - Massachusetts Institute of TechnologyAaron Kucyi - Stanford UniversityVitaly Napadow - Athinoula A. Martinos Center for Biomedical ImagingEmery N. Brown - Massachusetts General HospitalMarco L. Loggia - Athinoula A. Martinos Center for Biomedical ImagingOluwaseun Akeju - Massachusetts General Hospital
- Publication Details
- The Journal of neuroscience, v 37(29), pp 6938-6945
- Publisher
- Soc Neuroscience
- Number of pages
- 8
- Grant note
- P01AT006663 / National Center for Complementary & Integrative Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01NS094306 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) R01 AG053582; TR01 GM104948; P01-GM118269; R01 NS094306; OT2-OD023867; R61-AT009306; P01-AT006663; R01-AT007550; R01 AR064367 / National Institutes of Health Grants; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01AR064367 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) R01AG053582 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts P01GM118269 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) OT2OD023867 / OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Psychological and Brain Sciences (Psychology)
- Web of Science ID
- WOS:000405809700012
- Scopus ID
- 2-s2.0-85025131539
- Other Identifier
- 991021463542304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences