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