Association between serotonin denervation and resting-state functional connectivity in mild cognitive impairment

Research output: Contribution to journalArticle

Abstract

Resting-state functional connectivity alterations have been demonstrated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) before the observation of AD neuropathology, but mechanisms driving these changes are not well understood. Serotonin neurodegeneration has been observed in MCI and AD and is associated with cognitive deficits and neuropsychiatric symptoms, but the role of the serotonin system in relation to brain network dysfunction has not been a major focus of investigation. The current study investigated the relationship between serotonin transporter availability (SERT; measured using positron emission tomography) and brain network functional connectivity (measured using resting-state functional MRI) in 20 participants with MCI and 21 healthy controls. Two SERT regions of interest were selected for the analysis: the Dorsal Raphe Nuclei (DRN) and the precuneus which represent the cell bodies of origin and a cortical target of projections of the serotonin system, respectively. Both regions show decreased SERT in MCI compared to controls and are the site of early AD pathology. Average resting-state functional connectivity did not differ between MCI and controls. Decreased SERT in DRN was associated with lower hippocampal resting-state connectivity in MCI participants compared to controls. Decreased SERT in the right precuneus was also associated with lower resting-state connectivity of the retrosplenial cortex to the dorsal lateral prefrontal cortex and higher resting-state connectivity of the retrosplenial cortex to the posterior cingulate and in patients with MCI but not in controls. These results suggest that a serotonergic mechanism may underlie changes in brain functional connectivity in MCI.

Original languageEnglish (US)
JournalHuman Brain Mapping
DOIs
StateAccepted/In press - 2017

Fingerprint

Denervation
Serotonin
Alzheimer Disease
Parietal Lobe
Brain
Serotonin Plasma Membrane Transport Proteins
Cognitive Dysfunction
Gyrus Cinguli
Prefrontal Cortex
Positron-Emission Tomography
Magnetic Resonance Imaging
Observation
Pathology

Keywords

  • Functional magnetic resonance imaging (fMRI)
  • Individual differences
  • Positron emission tomography (PET)
  • Resting state functional magnetic resonance imaging (rs-fMRI)
  • Serotonin transporter

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology

Cite this

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title = "Association between serotonin denervation and resting-state functional connectivity in mild cognitive impairment",
abstract = "Resting-state functional connectivity alterations have been demonstrated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) before the observation of AD neuropathology, but mechanisms driving these changes are not well understood. Serotonin neurodegeneration has been observed in MCI and AD and is associated with cognitive deficits and neuropsychiatric symptoms, but the role of the serotonin system in relation to brain network dysfunction has not been a major focus of investigation. The current study investigated the relationship between serotonin transporter availability (SERT; measured using positron emission tomography) and brain network functional connectivity (measured using resting-state functional MRI) in 20 participants with MCI and 21 healthy controls. Two SERT regions of interest were selected for the analysis: the Dorsal Raphe Nuclei (DRN) and the precuneus which represent the cell bodies of origin and a cortical target of projections of the serotonin system, respectively. Both regions show decreased SERT in MCI compared to controls and are the site of early AD pathology. Average resting-state functional connectivity did not differ between MCI and controls. Decreased SERT in DRN was associated with lower hippocampal resting-state connectivity in MCI participants compared to controls. Decreased SERT in the right precuneus was also associated with lower resting-state connectivity of the retrosplenial cortex to the dorsal lateral prefrontal cortex and higher resting-state connectivity of the retrosplenial cortex to the posterior cingulate and in patients with MCI but not in controls. These results suggest that a serotonergic mechanism may underlie changes in brain functional connectivity in MCI.",
keywords = "Functional magnetic resonance imaging (fMRI), Individual differences, Positron emission tomography (PET), Resting state functional magnetic resonance imaging (rs-fMRI), Serotonin transporter",
author = "Frederick Barrett and Workman, {Clifford I.} and Haris Sair and Alena Savonenko and Kraut, {Michael A} and Sodums, {Devin J.} and Joo, {Jin Hui} and Najlla Nassery and Marano, {Christopher M.} and Cynthia Munro and Jason Brandt and Yun Zhou and Wong, {Dean Foster} and Gwenn Smith",
year = "2017",
doi = "10.1002/hbm.23595",
language = "English (US)",
journal = "Human Brain Mapping",
issn = "1065-9471",
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TY - JOUR

T1 - Association between serotonin denervation and resting-state functional connectivity in mild cognitive impairment

AU - Barrett, Frederick

AU - Workman, Clifford I.

AU - Sair, Haris

AU - Savonenko, Alena

AU - Kraut, Michael A

AU - Sodums, Devin J.

AU - Joo, Jin Hui

AU - Nassery, Najlla

AU - Marano, Christopher M.

AU - Munro, Cynthia

AU - Brandt, Jason

AU - Zhou, Yun

AU - Wong, Dean Foster

AU - Smith, Gwenn

PY - 2017

Y1 - 2017

N2 - Resting-state functional connectivity alterations have been demonstrated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) before the observation of AD neuropathology, but mechanisms driving these changes are not well understood. Serotonin neurodegeneration has been observed in MCI and AD and is associated with cognitive deficits and neuropsychiatric symptoms, but the role of the serotonin system in relation to brain network dysfunction has not been a major focus of investigation. The current study investigated the relationship between serotonin transporter availability (SERT; measured using positron emission tomography) and brain network functional connectivity (measured using resting-state functional MRI) in 20 participants with MCI and 21 healthy controls. Two SERT regions of interest were selected for the analysis: the Dorsal Raphe Nuclei (DRN) and the precuneus which represent the cell bodies of origin and a cortical target of projections of the serotonin system, respectively. Both regions show decreased SERT in MCI compared to controls and are the site of early AD pathology. Average resting-state functional connectivity did not differ between MCI and controls. Decreased SERT in DRN was associated with lower hippocampal resting-state connectivity in MCI participants compared to controls. Decreased SERT in the right precuneus was also associated with lower resting-state connectivity of the retrosplenial cortex to the dorsal lateral prefrontal cortex and higher resting-state connectivity of the retrosplenial cortex to the posterior cingulate and in patients with MCI but not in controls. These results suggest that a serotonergic mechanism may underlie changes in brain functional connectivity in MCI.

AB - Resting-state functional connectivity alterations have been demonstrated in Alzheimer's disease (AD) and mild cognitive impairment (MCI) before the observation of AD neuropathology, but mechanisms driving these changes are not well understood. Serotonin neurodegeneration has been observed in MCI and AD and is associated with cognitive deficits and neuropsychiatric symptoms, but the role of the serotonin system in relation to brain network dysfunction has not been a major focus of investigation. The current study investigated the relationship between serotonin transporter availability (SERT; measured using positron emission tomography) and brain network functional connectivity (measured using resting-state functional MRI) in 20 participants with MCI and 21 healthy controls. Two SERT regions of interest were selected for the analysis: the Dorsal Raphe Nuclei (DRN) and the precuneus which represent the cell bodies of origin and a cortical target of projections of the serotonin system, respectively. Both regions show decreased SERT in MCI compared to controls and are the site of early AD pathology. Average resting-state functional connectivity did not differ between MCI and controls. Decreased SERT in DRN was associated with lower hippocampal resting-state connectivity in MCI participants compared to controls. Decreased SERT in the right precuneus was also associated with lower resting-state connectivity of the retrosplenial cortex to the dorsal lateral prefrontal cortex and higher resting-state connectivity of the retrosplenial cortex to the posterior cingulate and in patients with MCI but not in controls. These results suggest that a serotonergic mechanism may underlie changes in brain functional connectivity in MCI.

KW - Functional magnetic resonance imaging (fMRI)

KW - Individual differences

KW - Positron emission tomography (PET)

KW - Resting state functional magnetic resonance imaging (rs-fMRI)

KW - Serotonin transporter

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U2 - 10.1002/hbm.23595

DO - 10.1002/hbm.23595

M3 - Article

JO - Human Brain Mapping

JF - Human Brain Mapping

SN - 1065-9471

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