Distinct Olfactory Cross-Modal Effects on the Human Motor System

BACKGROUND: Converging evidence indicates that action observation and action-related sounds activate cross-modally the human motor system. Since olfaction, the most ancestral sense, may have behavioural consequences on human activities, we causally investigated by transcranial magnetic stimulation (TMS) whether food odour could additionally facilitate the human motor system during the observation of grasping objects with alimentary valence, and the degree of specificity of these effects. METHODOLOGY/PRINCIPAL FINDINGS: In a repeated-measure block design, carried out on 24 healthy individuals participating to three different experiments, we show that sniffing alimentary odorants immediately increases the motor potentials evoked in hand muscles by TMS of the motor cortex. This effect was odorant-specific and was absent when subjects were presented with odorants including a potentially noxious trigeminal component. The smell-induced corticospinal facilitation of hand muscles during observation of grasping was an additive effect which superimposed to that induced by the mere observation of grasping actions for food or non-food objects. The odour-induced motor facilitation took place only in case of congruence between the sniffed odour and the observed grasped food, and specifically involved the muscle acting as prime mover for hand/fingers shaping in the observed action. CONCLUSIONS/SIGNIFICANCE: Complex olfactory cross-modal effects on the human corticospinal system are physiologically demonstrable. They are odorant-specific and, depending on the experimental context, muscle- and action-specific as well. This finding implies potential new diagnostic and rehabilitative applications

Results of Experiment 1.

<p>Mean percent changes of log-transformed MEP amplitude from hand muscles (FDI and ADM) versus the control condition Basal (the 100% reference line). The condition “Neutral” (N) was similar to Basal. Sniffing unimodal olfactory (O), bimodal olfacto-gustative (OG), and natural odorants as <i>coffee</i> and <i>mortadella</i> increased MEPs' size. Such facilitation of corticospinal output disappeared when sniffing odorants with a trigeminal component (OT and OTG, grey area). Notably, no cognitive tasks except sniffing are required to subjects. Statistics are in the text.</p

Results of Experiment 2 (Food vs Soap).

<p>Graphical representations of the main significant interactions: a) an higher MEP increase occurred when the subjects observed a grasping movement toward a food object than toward a non-food object; b) an higher MEP increase occurred when the subjects smelled a food object than a non-food object</p

Results of Experiment 3.

<p>Mean percentual changes of MEP amplitude versus “<i>Basal</i>” in the FDI muscle, which was prime mover for the observed grasping action, and in the ADM muscle which has no functional role in grasping. Only the congruency between the odour of <i>bombolone</i> with the observation of grasping a <i>bombolone,</i> but not other food or non-food objects, produced a significant increase of MEP size, which selectively took place in the prime mover. No changes are observed in the ADM muscle. Statistics are in the text.</p

Results of Experiment 2 (only food objects).

<p>Graphical representations of the main significant interactions: a) an higher MEP increase occurred in FDI than in ADM when the subjects observed a grasping movement; b) similarly, an higher MEP increase occurred in FDI than in ADM when the subjects smelled a food; c) even if “smelling” produces a lower MEP increase with, than without, concomitant grasping observation, a significant further facilitation (27% in the original µV scale) was found.</p

Experimental designs.

<p>Panel a): The two hand muscle from which motor evoked potentials (MEPs) were recorded. Panel b): Experiment 2. Here, the four food or non-food objects were separately presented. Within each of these main conditions, subjects were asked to observe the grasping (with or without the corresponding odour) or to simply smell the object without observing food or soap. “Salame” is the Italian name of salami, “Mortadella” represents the English term “balony”, and “Bombolone” is the Italian word to define something like a custard filled donut. Panel c): Experiment 3. Here, the four objects were simultaneously presented. The subjects smelled a single odorant (i.e.,<i>bombolone</i>), while observing the experimenter reaching and grasping three edible objects (one of which was <i>bombolone</i>) or a non-edible object of a similar shape (soap).</p

The Genetic Landscape of Dystrophin Mutations in Italy: A Nationwide Study

Dystrophinopathies are inherited diseases caused by mutations in the dystrophin (DMD) gene for which testing is mandatory for genetic diagnosis, reproductive choices and eligibility for personalized trials. We genotyped the DMD gene in our Italian cohort of 1902 patients (BMD n = 740, 39%; DMD n =1162, 61%) within a nationwide study involving 11 diagnostic centers in a 10-year window (2008-2017). In DMD patients, we found deletions in 57%, duplications in 11% and small mutations in 32%. In BMD, we found deletions in 78%, duplications in 9% and small mutations in 13%. In BMD, there are a higher number of deletions, and small mutations are more frequent than duplications. Among small mutations that are generally frequent in both phenotypes, 44% of DMD and 36% of BMD are nonsense, thus, eligible for stop codon read-through therapy; 63% of all out-of-frame deletions are eligible for single exon skipping. Patients were also assigned to Italian regions and showed interesting regional differences in mutation distribution. The full genetic characterization in this large, nationwide cohort has allowed us to draw several correlations between DMD/BMD genotype landscapes and mutation frequency, mutation types, mutation locations along the gene, exon/intron architecture, and relevant protein domain, with effects on population genetic characteristics and new personalized therapies