Involvement of Subcortical Brain Structures During Olfactory Stimulation in Multiple Chemical Sensitivity

Abstract

Multiple chemical sensitivity (MCS) patients usually react to odour compounds and the majority of neuroimaging studies assessed, especially at the cortical level, many olfactory-related correlates. The purpose of the present study was to depict sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory stimulation by using a recently validated (18)F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computer tomography procedure in 26 MCS and 11 healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve subcortical volumes of interest were identified by the automated anatomical labeling library and normalized to thalamus FDG uptake. In both groups, when comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased metabolism in bilateral putamen and hippocampus and a relative increased metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum. The between-groups ANOVA demonstrated in MCS a significant higher metabolism in bilateral OLF during NC. As in HC subjects negative correlations were found in OC between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness scale, the latter positively correlated with MCS subjects' bilateral putamen FDG uptake in OC. Besides FDG uptake resemblances in both groups were found, for the first time a relative higher metabolism increase in OLF in MCS subjects at rest with respect to HC was found. When merging this aspect to the different subcortical FDG uptake correlations patterns in the two groups, the present study demonstrated to describe a peculiar metabolic index of behavioral and neurological aspects of MCS complaints.

Deranged Dimensionality of Vestibular Re-Weighting in Multiple Chemical Sensitivity

“…For instance, many studies have tried to find an unifying pathophysiology for all IEIs, focusing on CNS reactions to environmental stimuli, with activation changes of the brain areas related to sensory processing and emotional responses [1,[5][6][7][8][9][10][11][12][13][14][15]41,42]. Since environmental noise has been recognised as an important health quality stressor [43], relevant literature up to now has focused mainly on auditory symptoms [21,22] without highlighting possible vestibular and postural consequences.…”

“…Possible explanations for the rearranged model along vestibular processing and symptoms cohort referred to by MCS patients could be considered to reside within pathophysiological cascades, such as those involving limbic structures in the natural history of MCS [1,[4][5][6][7][8][9][10][11][12][13][14][15]. According to these notions, repeated exposure to MCS inducing agents were found to provide in MCS subjects both time-dependent sensitization and kindling, especially within hippocampal and limbic areas [65].…”

“…However, the altered CNS responses are hypothesized to be paralleled by increased anxiety, avoidance, anticipatory stress [9] and attention bias [6] to chemical exposure. According to these theories, several studies in the last few years have shown cerebral blood flow distribution abnormalities in patients with MCS, especially while processing odorous substances [10][11][12]. In particular, MCS sufferers have been seen to react peculiarly to sensory stimuli, with activation of brain areas connected with motivational, emotional and non-conscious processing of information, such as the amygdala and the hippocampus, encompassed in the limbic system [10][11][12][13][14], whose pathways are known to mediate CNS sensitization and their dysregulation contributes to abnormalities of behaviour and mood, endocrine, autonomic and immune function [15].…”

“…Thus, due to (i) the overlapping psychogenic and organic burdens that, below the level of consciousness, are shared not only in MCS development but also in the vestibular disorders [1,[10][11][12][13][15][16][17]20]; (ii) the number of previous studies describing central processing impairment related to inner ear inflow in this syndrome [21,22]; and (iii) the lack of literature on clinical evidence of the presentation of dizziness [2,3], the purpose of the present exploratory study was to highlight the possible MCS hidden clinical/subclinical aspects of vestibular impairment by inferential and principal component (PC) analysis applied on the contribution of recently implemented otoneurological testings. This, with the aim of disclosing possible implementations in diagnosing and monitoring undiscovered aspects underpinning the natural history of MCS, will possibly assist in suggesting future treatment choices in a clinical setting.…”

Association of Odor Thresholds and Responses in Cerebral Blood Flow of the Prefrontal Area during Olfactory Stimulation in Patients with Multiple Chemical Sensitivity

“…Several studies in the past decade uncovered regional cerebral blood flow (rCBF) distribution abnormalities in patients with MCS using single-photon emission computed tomography (SPECT) [12] and positron emission tomography (PET) [13–15], especially while processing odorous substances. In particular, patients with MCS were demonstrated to peculiarly react to sensory stimuli, with activation of brain areas connected with motivational and emotional processing of the information.…”