A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis

Andrew Schrepf; Chelsea M. Kaplan; Eric Ichesco; Tony Larkin; Steven E. Harte; Richard E. Harris; Alison D. Murray; Gordon D. Waiter; Daniel J. Clauw; Neil Basu

doi:10.1038/s41467-018-04648-0

A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis

Andrew Schrepf^* (Corresponding Author), Chelsea M. Kaplan, Eric Ichesco, Tony Larkin, Steven E. Harte, Richard E. Harris, Alison D. Murray, Gordon D. Waiter, Daniel J. Clauw, Neil Basu

^*Corresponding author for this work

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Abstract

It is unknown how chronic inflammation impacts the brain. Here, we examined whether higher levels of peripheral inflammation were associated with brain connectivity and structure in 54 rheumatoid arthritis patients using functional and structural MRI. We show that higher levels of inflammation are associated with more positive connections between the inferior parietal lobule (IPL), medial prefrontal cortex, and multiple brain networks, as well as reduced IPL grey matter, and that these patterns of connectivity predicted fatigue, pain and cognitive dysfunction. At a second scan 6 months later, some of the same patterns of connectivity were again associated with higher peripheral inflammation. A graph theoretical analysis of whole-brain functional connectivity revealed a pattern of connections spanning 49 regions, including the IPL and medial frontal cortex, that are associated with peripheral inflammation. These regions may play a critical role in transducing peripheral inflammatory signals to the central changes seen in rheumatoid arthritis.

Original language	English
Article number	2243
Number of pages	11
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-04648-0
Publication status	Published - 8 Jun 2018

Keywords

Chronic inflammation
Neural circuits
Neuroimmunology
Rheumatoid arthritis

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10.1038/s41467-018-04648-0Licence: CC BY

A multi-modal MRI study of the central response to in fl ammation in rheumatoid arthritis
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Final published version, 1.22 MBLicence: CC BY

Gordon Waiter
Person: Academic

Cite this

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title = "A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis",

abstract = "It is unknown how chronic inflammation impacts the brain. Here, we examined whether higher levels of peripheral inflammation were associated with brain connectivity and structure in 54 rheumatoid arthritis patients using functional and structural MRI. We show that higher levels of inflammation are associated with more positive connections between the inferior parietal lobule (IPL), medial prefrontal cortex, and multiple brain networks, as well as reduced IPL grey matter, and that these patterns of connectivity predicted fatigue, pain and cognitive dysfunction. At a second scan 6 months later, some of the same patterns of connectivity were again associated with higher peripheral inflammation. A graph theoretical analysis of whole-brain functional connectivity revealed a pattern of connections spanning 49 regions, including the IPL and medial frontal cortex, that are associated with peripheral inflammation. These regions may play a critical role in transducing peripheral inflammatory signals to the central changes seen in rheumatoid arthritis.",

keywords = "Chronic inflammation, Neural circuits, Neuroimmunology, Rheumatoid arthritis",

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note = "Special thanks to the patient community who participated in this research effort. Thanks to Mariella D{\textquoteright}Allesandro for efforts towards recruitment.",

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AU - Kaplan, Chelsea M.

AU - Ichesco, Eric

AU - Larkin, Tony

AU - Harte, Steven E.

AU - Harris, Richard E.

AU - Murray, Alison D.

AU - Waiter, Gordon D.

AU - Clauw, Daniel J.

AU - Basu, Neil

N1 - Special thanks to the patient community who participated in this research effort. Thanks to Mariella D’Allesandro for efforts towards recruitment.

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N2 - It is unknown how chronic inflammation impacts the brain. Here, we examined whether higher levels of peripheral inflammation were associated with brain connectivity and structure in 54 rheumatoid arthritis patients using functional and structural MRI. We show that higher levels of inflammation are associated with more positive connections between the inferior parietal lobule (IPL), medial prefrontal cortex, and multiple brain networks, as well as reduced IPL grey matter, and that these patterns of connectivity predicted fatigue, pain and cognitive dysfunction. At a second scan 6 months later, some of the same patterns of connectivity were again associated with higher peripheral inflammation. A graph theoretical analysis of whole-brain functional connectivity revealed a pattern of connections spanning 49 regions, including the IPL and medial frontal cortex, that are associated with peripheral inflammation. These regions may play a critical role in transducing peripheral inflammatory signals to the central changes seen in rheumatoid arthritis.

AB - It is unknown how chronic inflammation impacts the brain. Here, we examined whether higher levels of peripheral inflammation were associated with brain connectivity and structure in 54 rheumatoid arthritis patients using functional and structural MRI. We show that higher levels of inflammation are associated with more positive connections between the inferior parietal lobule (IPL), medial prefrontal cortex, and multiple brain networks, as well as reduced IPL grey matter, and that these patterns of connectivity predicted fatigue, pain and cognitive dysfunction. At a second scan 6 months later, some of the same patterns of connectivity were again associated with higher peripheral inflammation. A graph theoretical analysis of whole-brain functional connectivity revealed a pattern of connections spanning 49 regions, including the IPL and medial frontal cortex, that are associated with peripheral inflammation. These regions may play a critical role in transducing peripheral inflammatory signals to the central changes seen in rheumatoid arthritis.

KW - Chronic inflammation

KW - Neural circuits

KW - Neuroimmunology

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A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis

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