Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation

Lekander, Mats; Karshikoff, Bianka; Johansson, Emilia; Soop, Anne; Fransson, Peter; Lundström, Johan N.; Andréasson, Anna; Ingvar, Martin; Petrović, Predrag; Axelsson, John; Nilsonne, Gustav

doi:10.1016/j.bbi.2015.12.018

Cited by 63 publications

(41 citation statements)

References 33 publications

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“…The superior and middle frontal gyrus seemed to reflect sickness-driven visual processing in parts of the cortical face-processing network (32). They may, together with the insula, amygdala, and the middle cingulate cortex, point toward the presence of facial emotion recognition (32) or to shared neural representations (33) of a firsthand experience of an emotion-like state such as feeling sick (26). Although this interpretation remains speculative because participants lacked an actual firsthand experience, the donors depicted in the facial photographs felt more sick and anxious after LPS treatment than after placebo saline treatment, as reported earlier (22).…”

Section: Discussionmentioning

confidence: 99%

“…This notion supports the earlier assumption of olfactory-sickness-driven OFC and MDT activation, suggested to be part of a neural circuitry serving disease avoidance. Last, the middle cingulate cortex has recently been found to exhibit enhanced connectivity with the anterior insula during a first-hand experience of LPS-induced inflammation (26), and this enhancement has been interpreted as a potential neurophysiological mechanism involved in the brain's sickness response. Applied to the current data, the middle cingulate cortex, in the context of multisensory-sickness-driven associations between IPS and whole-brain activations, may indicate a shared representation of an inflammatory state and associated discomfort.…”

Section: Discussionmentioning

confidence: 99%

“…We also investigated the combined multisensory olfactoryvisual sickness signal in areas that detect own sickness and, potentially, sickness in others, such as the orbitofrontal cortex, posterior cingulate cortex, and insula (26). We specifically tested whether the neural correlates of combined olfactory-visual sickness cues would cause activation to and above the sum (superadditive) of the olfactory and visual sickness cue profiles, thus representing the presence of multisensory integration of human sickness signals.…”

Section: Significancementioning

confidence: 99%

See 2 more Smart Citations

Behavioral and neural correlates to multisensory detection of sick humans

Regenbogen

Axelsson

Lasselin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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119

110

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Throughout human evolution, infectious diseases have been a primary cause of death. Detection of subtle cues indicating sickness and avoidance of sick conspecifics would therefore be an adaptive way of coping with an environment fraught with pathogens. This study determines how humans perceive and integrate early cues of sickness in conspecifics sampled just hours after the induction of immune system activation, and the underlying neural mechanisms for this detection. In a double-blind placebo-controlled crossover design, the immune system in 22 sample donors was transiently activated with an endotoxin injection [lipopolysaccharide (LPS)]. Facial photographs and body odor samples were taken from the same donors when "sick" (LPS-injected) and when "healthy" (saline-injected) and subsequently were presented to a separate group of participants (n = 30) who rated their liking of the presented person during fMRI scanning. Faces were less socially desirable when sick, and sick body odors tended to lower liking of the faces. Sickness status presented by odor and facial photograph resulted in increased neural activation of odor-and faceperception networks, respectively. A superadditive effect of olfactory-visual integration of sickness cues was found in the intraparietal sulcus, which was functionally connected to core areas of multisensory integration in the superior temporal sulcus and orbitofrontal cortex. Taken together, the results outline a disease-avoidance model in which neural mechanisms involved in the detection of disease cues and multisensory integration are vital parts.body odor | lipopolysaccharide | endotoxin | sickness cues | disease avoidance

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

See 1 more Smart Citation

Behavioral and neural correlates to multisensory detection of sick humans

Regenbogen

Axelsson

Lasselin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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119

110

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“…This research is still in its infancy, but bears great potential for understanding potential mechanisms. Inflammation has been shown to affect intrinsic connectivity (134–136) and, for instance, the connectivity between the insula and mid-cingulate cortex seems associated with the inflammation-induced state of malaise and discomfort, in line with the interoceptive role of insula (136). Although this has not yet been studied in relation to fatigue, it is probable that altered connections between structures, in addition to specific structural changes, also contribute to the development of fatigue (97, 137).…”

Section: Potential Neuronal Mechanisms Underlying Dimensions Of Inflamentioning

confidence: 99%

Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms

2017

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Fatigue is a highly disabling symptom in various medical conditions. While inflammation has been suggested as a potential contributor to the development of fatigue, underlying mechanisms remain poorly understood. In this review, we propose that a better assessment of central fatigue, taking into account its multidimensional features, could help elucidate the role and mechanisms of inflammation in fatigue development. A description of the features of central fatigue is provided, and the current evidence describing the association between inflammation and fatigue in various medical conditions is reviewed. Additionally, the effect of inflammation on specific neuronal processes that may be involved in distinct fatigue dimensions is described. We suggest that the multidimensional aspects of fatigue should be assessed in future studies of inflammation-induced fatigue and that this would benefit the development of effective therapeutic interventions.

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“…LPS injection triggers increased inflammatory cytokines, which correlate with sickness behaviors and underlying changes in brain activity (3, 4). However, use of LPS evokes a strong immune response and pro-inflammatory cytokine elevations 2–10 times baseline levels even at low doses and causes significant changes in vital signs and physical discomfort in subjects receiving it (5).…”

Section: Introductionmentioning

confidence: 99%

Pilot investigation into the sickness response to influenza vaccination in adults: Effect of depression and anxiety

Harper

South

Trivedi

et al. 2017

General Hospital Psychiatry

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Objective To determine whether depressed or anxious patients experience greater affective change than mentally healthy individuals following influenza vaccination. Methods Participants (n = 112) completed the Positive and Negative Affect Schedule (PANAS) before influenza vaccination and 1–2 days post-vaccination (M = 32.3 hours). Pre- and post-vaccination PANAS scores were compared using two-tailed, paired-samples t-tests. Change in positive affect between participants with depression or anxiety and those without was compared using two-way ANOVA. Follow up positive affect was further examined using multiple linear regression. Results Positive affect decreased following vaccination (M = 2.18, 95% CI [1.07, 3.29], t(111) = 3.89, p < .001) for all participants and was more pronounced for those with anxiety or depression (F(1, 110) = 7.51, p = .009). Similarly, predicted follow up affect score was higher for those without a mental health conditions (β = 3.67, 95% CI [1.18, 6.16], t(103) = 2.92, p = .004). Conclusions These data suggest that influenza vaccine has a greater effect on affect in patients with depression and anxiety than in mentally healthy individuals. This effect was focused on positive affect, suggesting that influenza vaccine induced inflammation may be best suited to examine alterations in positive affect and positive valence systems.

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Intrinsic functional connectivity of insular cortex and symptoms of sickness during acute experimental inflammation

Cited by 63 publications

References 33 publications

Behavioral and neural correlates to multisensory detection of sick humans

Behavioral and neural correlates to multisensory detection of sick humans

Role of Inflammation in Human Fatigue: Relevance of Multidimensional Assessments and Potential Neuronal Mechanisms

Pilot investigation into the sickness response to influenza vaccination in adults: Effect of depression and anxiety

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