Higher Peripheral Inflammatory Signaling Associated With Lower Resting-State Functional Brain Connectivity in Emotion Regulation and Central Executive Networks

Nusslock, Robin; Brody, Gene H.; Armstrong, Casey C.; Carroll, Ann; Sweet, Lawrence H.; Yu, Tianyi; Barton, Allen W.; Hallowell, Emily S.; Chen, Eric; Higgins, James; Parrish, Todd B.; Wang, Lei; Miller, Gregory E.

doi:10.1016/j.biopsych.2019.03.968

Cited by 77 publications

(50 citation statements)

References 67 publications

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“…positive and negative scenes). Finally, although several psychoneuroimmunological studies have examined the associations between inflammation and functional connectivity while individuals are at rest ( Felger et al., 2016 ; Lekander et al., 2016 ; Marsland et al ., 2017a ; Mehta et al., 2018 ; Kraynak et al., 2019 ; Nusslock et al., 2019 ), few known studies have examined how markers of systemic inflammation might relate to functional connectivity while participants are engaged in a dynamic affective reactivity task. In several studies, task-based connectivity has been shown to outperform resting-state models for detecting relationships between neural activity and individuals’ differences in behavior ( Greene et al., 2018 ; Jiang et al., 2020 ), suggesting that investigations of associations between inflammation and task-based connectivity are warranted.…”

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confidence: 99%

Systemic inflammation is associated with differential neural reactivity and connectivity to affective images

Alvarez

Hackman

Miller

et al. 2020

Social Cognitive and Affective Neuroscience

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Abstract Systemic inflammation is increasingly appreciated as a predictor of health and well-being. Further, inflammation has been shown to influence and be influenced by affective experiences. Although prior work has substantiated associations between inflammatory and affective processes, fewer studies have investigated the neurobiological correlates that underlie links between systemic, low-grade inflammation and affective reactivity. Thus, the current study examined whether markers of systemic inflammation (i.e. interleukin-6, C-reactive protein) are associated with differential patterns of neural activation and connectivity in corticolimbic regions in response to affective images. We investigated this question in a sample of 66 adults (44 women, M age = 54.98 years, range = 35–76) from the Midlife in the United States study. Higher levels of inflammation were associated with lower activity in limbic regions (i.e. amygdala, hippocampus, anterior insula, temporal pole) when viewing positive (vs neutral) images. Higher levels of inflammation were also associated with greater connectivity between the hippocampus and the medial prefrontal cortex in response to positive images. Inflammatory markers were not associated with significant differences in activation or connectivity to negative images. These findings highlight the utility of health neuroscience approaches in demonstrating that physiological processes such as inflammation are related to how our brains respond to affective information.

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confidence: 99%

Systemic inflammation is associated with differential neural reactivity and connectivity to affective images

Alvarez

Hackman

Miller

et al. 2020

Social Cognitive and Affective Neuroscience

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“…The use of a composite pro-inflammatory score has previously been used to investigate the relation between IL-1β, IL-6, TNF-α, INF-γ, CRP, and combat exposed males with PTSD compare to combat exposed males without PTSD [54]. Other studies have chosen to sum z-score transformed concentrations for each marker [55][56][57]. We performed analyses deriving composite pro-inflammatory scores both ways, and yielded the same results regardless of computational method.…”

Section: Methodsmentioning

confidence: 99%

Inflammation and Trauma-Related Psychopathology in Syrian and Iraqi Refugees

Grasser

Burghardt

Daugherty

et al. 2020

Behavioral Sciences

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Refugees experience high rates of post-traumatic stress disorder (PTSD), anxiety, and depression due to exposure to civilian war trauma and forced migration. Inflammatory products may offer viable biological indicators of trauma-related psychopathology in this cohort, promoting rapid and objective assessment of psychopathology. Incoming Syrian and Iraqi refugees (n = 36) ages 18-65 completed self-report measures of PTSD, anxiety, and depression and provided saliva samples during an assessment at a primary care clinic within the first month of resettlement in the United States. Interleukin 1β (IL-1β) and C-reactive protein (CRP) differentially correlated with symptom severity by domain, and there was a non-significant trend for sex moderating the relation between inflammation and PTSD symptoms. Our findings show unique relations between trauma-related psychopathology and inflammation. There is a need for further research in diverse ethnic cohorts with differential trauma exposures for inflammation to be considered a biological indicator of psychopathology.

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“…However, to date no study has investigated how these cells relate to brain function in humans. In this issue of Biological Psychiatry, Nusslock et al (5) address these issues in two well powered studies that combine molecular (and in the second study cellular) inflammatory markers with resting-state (rs) functional MRI (fMRI).…”

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confidence: 99%

“…This study has a number of important strengths and implications. Firstly, by repeating their analyses in two independent cohorts, Nusslock et al (5) demonstrate that a composite index of inflammation (combining C-reactive protein (CRP), Interleukin (IL)-6, IL-10 and tumor necrosis factor (TNF)-alpha) negatively scales with functional connectivity within the emotional regulation network across both cohorts i.e. individuals with a higher inflammatory index showed weaker function connectivity within this network.…”

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confidence: 99%

“…Nusslock et al's (5) finding of an association between circulating classical monocytes and decreased functional connectivity within emotion regulation networks in the second ostensibly healthy adolescent cohort has potentially important implications. It raises questions about how broadly monocyte trafficking to the brain influences human brain function in apparent health and the importance of this mechanism in psychiatric disorders, particularly post-traumatic stress, depression and anxiety.…”

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confidence: 99%

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Disentangling the Effects of Peripheral Inflammatory Markers on Brain Functional Connectivity

Harrison

2019

Biological Psychiatry

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Higher Peripheral Inflammatory Signaling Associated With Lower Resting-State Functional Brain Connectivity in Emotion Regulation and Central Executive Networks

Cited by 77 publications

References 67 publications

Systemic inflammation is associated with differential neural reactivity and connectivity to affective images

Systemic inflammation is associated with differential neural reactivity and connectivity to affective images

Inflammation and Trauma-Related Psychopathology in Syrian and Iraqi Refugees

Disentangling the Effects of Peripheral Inflammatory Markers on Brain Functional Connectivity

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