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Table 1 Summary of experimental human studies associated with CI and related neurological responses or brain imaging in chemical provocation tests

From: Chemical intolerance: involvement of brain function and networks after exposure to extrinsic stimuli perceived as hazardous

Study, year with reference Type of analysis Subjects (CI or MCS/control) Substances Exposure time Measurement Findings
Alessandrini et al. 2016 [38] PET with18FDG uptake 26/11 Saline, vanillin 9 min After 24 min of exposure Different subcortical olfactory processing and an increased responsiveness in the central nervous system and olfactory center
Andersson et al. 2009 [39] EEG, EOG 21/17 CO2, amyl acetate (banana smelling), sound 200 ms repetition, 72 stimuli during 1.5 h During task Attention bias and enhanced sensitization, and alterations in central, cognitive responses to chemical exposure
Andersson et al. 2014 [40] fMRI 25/26 CO2, isoamyl acetate (banana smelling, below irritation threshold) 20 repetitions of 30 s During task Not characterized by hyperresponsiveness in sensory areas and interpreted as a limbic hyperactivity and speculatively as an inability to inhibit salient external stimuli
Andersson et al. 2016 [23] Autonomic recordings 18/18 n-Butanol (below irritation threshold) 42 min During task Altered autonomic responses (higher pulse rate and lower pulse rate variability) and chemosensory perception during chemical exposure
Andersson et al. 2017 [41] fMRI 14 olfactory sensitizers, 20 intermediate, and 15 habituaters CO2, isoamyl acetate (banana smelling, below irritation threshold) 20 repetitions of 30 s During task In reanalysis of Andersson et al. (2014) [40], greater reactions in regions relevant for pain and saliency detection, and olfactory projection areas (olfactory region of the orbitofrontal cortex)
Azuma et al. 2013 [32] fNIRS 12/11 Odorants (mandarin orange, perfume, Japanese cypress, and menthol) 10 s During exposure Activation in the prefrontal cortex during exposure. Poorer autonomic perception and negative affectivity. Altered prefrontal information processing associated with odor processing and memory and cognition processes
Azuma et al. 2015 [33] fNIRS 6/6 Odorants (mandarin orange, perfume, Japanese cypress, and menthol) 10 s After exposure Activation in the orbitofrontal cortex after exposure. Altered prefrontal information processing associated with odor processing and memory and cognition processes
Azuma et al. 2016 [34] fNIRS 10/6 Odorants (sweet and fecal) 10 s During and after exposure Activation in the prefrontal cortex and orbitofrontal cortex. Altered prefrontal information processing associated with odor processing and memory and cognition processes
Bornschein et al. 2008 [42] Serum cortisol, cognitive performance 20/17 Solvent mixture of hydrocarbons (below odor threshold) 3 repetitions of 15 min Before and after the exposure No differences
Chiaravalloti et al. 2015 [43] PET with18FDG uptake 26/11 Saline, vanillin 9 min After 24 min of exposure Different cortical olfactory processing with deactivation that mainly involves the frontal cortex and by active recruitment of the left inferior temporal gyrus
Claeson et al. 2017 [44] SCA, sensory irritation 18/19 Acrolein, heptan 60 min Before exposure, after and 24 h postexposure No differences in SCA, greater sensory irritation, suggesting altered trigeminal reactivity
Claeson et al. 2017 [45] Serum oxylipins and endocannabinoids 18/19 Acrolein, heptan 60 min Before exposure, after and 24 h postexposure No differences
Dantoft et al. 2015 [46] Cytokine and chemokine in epithelial lining fluid 18/18 n-Butanol (below irritation threshold) 42 min After 15 min of exposure No abnormal upper airway inflammatory mediator levels
Dantoft et al. 2017 [47] Gene expression for inflammatory markers 18/18 n-Butanol (below irritation threshold) 42 min After 15 min of exposure No differences in gene expression levels before/after exposure
Georgellis et al. 2003 [48] Serum prolactin and cortisol 14/15 Furfuryl mercaptan, acetone, VOC mixture 20 min Before and after exposure No differences
Haumann et al. 2003 [49] RR, HR 12/12 Ethyl benzene, 2-butanone, 2-propanol, 1-octanol (above odor threshold) 4 h During exposure No differences
Hillert et al. 2007 [50] PET 12/12 Vanillin, odorant acetone, cedar oil, lavender oil, eugenol, butanol, human pheromones (above odor threshold) 15 s During task Activated odor-processing brain regions with odorant-related increase in activation of the anterior cingulate cortex and cuneus–precuneus
Joffres et al. 2005 [51] SCA, HR, EMG, RR, cognitive test 10/7 Glue, body wash solution, dryer sheet, unscented shampoo 5 min During task Increased skin conductance, suggesting involvement of the premotor cortex, hypothalamus, and limbic systems
Kimata 2004 [52] Plasma SP, VIP, NGF, and histamine, and skin prick tests 25/25 Plastic-based paint with unpleasant odor containing organic solvents 15 min Before and after exposure Increased plasma levels of all parameters, suggesting enhanced neurogenic inflammation
Millqvist et al. 2005 [53] NGF, nasal lavage fluid 13 sensory hyperreactivity /14 Capsaicin Over 6 min (until inducing coughing) Before and after exposure Increased NGF
Orriols et al. 2009 [54] SPECT 8/8 Plastic-based paint, perfume, petrol, glutaraldehyde (above odor threshold) 3–35 min (until inducing symptoms) After 15–30 min of exposure Neurocognitive impairment and dysfunction particularly in odor-processing areas, suggesting a neurogenic origin
Osterberg et al. 2003 [55] Neurobehavioral test 10/20 n-Butyl acetate, toluene (above odor threshold) 70 min During exposure Lower psychological test performance during exposure
Papo et al. 2006 [56] EEG 23/23 Phenyl ethyl alcohol, hydrogen sulfide (above odor threshold) 200 ms repetition During task No differences
  1. Abbreviations: CI chemical intolerance, CO2 carbon dioxide, EEG electroencephalograph, EMG surface electromyogram, EOG electrooculogram, FDG F-2-fluoro-2-deoxy-D-glucose, fMRI functional magnetic resonance imaging, fNIRS functional near-infrared spectroscopy, HR heart rate, MCS multiple chemical sensitivity, NGF nerve growth factor, PET positron emission tomography, RR respiratory rate, SCA skin conductance activity, SP substance P, SPECT single photon-emission computed tomography, VIP vasoactive intestinal peptide, VOC volatile organic compound