On trigeminality

The trigeminality of the odor had a surprising effect at the physiological but not at the behavioral level, since conditioned GSRs were sensitive to valence when odors were trigeminal only. In general, all conditioned GSRs were higher for trigeminal smells, irrespectively of the valence, replicating results obtained previously (Czerniawska, Zegardło, & Wojciechowski, 2013). Trigeminal odors have been shown to recruit more neural resources when processed outside of attentional focus, than non-trigeminal odors (Geisler & Murphy, 2000), and to. They are able to interfere with face processing, and this could stem from an attentional competition for attentional resources, as suggested by (Walla et al., 2005), and (Michael, 2003) ., who found that trigeminal odors increase the amplitude of the effects of visual attentional capture. An interesting experiment of memory induction by (Czerniawska et al., 2013) revealed that trigeminal odors often evoked memories that were both rated as higher in clarity and lower in happiness, compared to non-trigeminal odors, regardless of their valence. This study thus proposed to consider the trigeminal system as playing a crucial alerting function in the coding and retrieval of survival-related memories, since “High clarity indicates better recall of an episode and may allow quicker and more accurate reaction in an analogous situation”.

Along with our results, these studies confirm the role of the trigeminal feature in terms of attentional modulation, whether the odor is pleasant or not. More generally, they stress the importance of considering trigeminality when it comes to studying odor-borne interferences with cognitive processes.

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General discussion

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Summary of the main findings 1

The aim of this thesis work was to investigate the mechanisms underlying the representation and the influence of odor borne feelings at the behavioral, physiological and neural levels. The four main objectives of the experimental work presented in the previous chapter were the following: (1) to validate the use of an MRI Compatible Olfactometer (MCO) as a reliable tool for the elicitation of affective olfactory experiences in an MRI environment; (2) to address the representation of complex olfactory feelings in the brain beyond valence only; (3) to study the modulation of emotional processing of olfactory stimuli by endogenous attention; (4) to assess whether an affective context brought by odor could affect associative aversive learning processes either congruently (affective congruency in an aversive context) or incongruently (enhanced awareness brought by a positive context, “Broaden and Build”).

In the MCO validation prestudy, we characterized the influence of various parameters (air debit, stimulus repetition) on odor delivery and perception. We verified that the opening of an odor valve did not cause a change in pressure compared to the ISI air, and thus that the resulting odor event was not biased by a tactile sensation. We also determined the latency occurring between the opening of an odor valve and the arrival of the corresponding odor into the participant’s nose as a function of a given air flow. The analysis of odor perception at the behavioral and neural levels confirmed that participants reliably detected odor from control events, and that repeated (>12) olfactory stimulations elicited activities in odor related areas in the brain. Finally, we also assessed differential analysis methods (classical GLM, ROI activity time courses, FIR model) for the characterization of olfactory-related signal in the brain. The outcomes of this prestudy were used as standards for the design of the two MRI experiments presented in this work (Study 1 and 2)

In study 1, we derived neural patterns of activation from a-posteriori, verbal measurements of complex odor-born feelings, and we were able to measure the additional information conveyed by these differentiated patterns compared to valence. These results confirmed the existence of functionally-determined (Chrea et al., 2009) representations of odor-specific feelings in the brain that go beyond the simple valence, in accordance with the functional relevance of odors (e.g. disgust, appetite regulation).

In study 2, we found that audition and olfaction were differentially modulated by endogenous attention, since auditory cortices were upregulated when attention was directed to sounds, while olfactory areas were not affected when attention was directed to odors or away from them.

Interestingly, the influence of attention on brain areas responsible for the processing of olfactory valence (pleasant or unpleasant odors) was however unequal. The medial OFC (sensitive to pleasant

177 odors) and the right insula (sensitive to unpleasant odors) were impacted by odor valence only, whereas the left insula was sensitive to valence only when unpleasant odors were attend to. Finally, the amygdala and the piriform cortex remained unaffected by the attentional manipulation.

In study 3, we showed that the outcome of associative aversive learning (CS: angry faces, US, unpleasant white noise) was changed by the presence an affective odor context. In particular resistance to extinction was observed behaviorally and physiologically when performed with unpleasant odors, while no association specific effects were noticed with pleasant odors, which only appeared to enhance the awareness to aversive stimuli (CS/US) in general. Interestingly, the trigeminality of odors appeared to affect the physiological but not the behavioral indicators.

Given that the previous results were extensively discussed in each of the experimental respective sections, we will know summarize the theoretical relevance of the findings obtained for key olfactory brain areas.

Cerebral regions involved in the processing of odor-borne 2

emotions

The results obtained in this thesis work confirm that several brain areas, involved in motor, memory, valence processing are affected by odor stimulation. Olfactory perception thus mobilizes several neural networks – beyond olfactory areas only – that are known for their influential action on behavior.

2.1 Amygdala, intensity & arousal

In line with previous findings, amygdala was activated bilaterally by olfactory stimulation, whether it was cued and thus expected (O>NO contrasts from preliminary experiment and study 1, and O>S localizer from study 2), or unexpected (OS>S contrast from study 2), and was also sensitive to odor intensity (I+ contrast in study 1). These activations consistently overlapped (Figure 55a, overlap in white) central to dorsomedially around the periamygdaloid cortex and the amygdalar cortical nuclei (see section 2.4.4 in the theoretical part, and also de Olmos, Hardy, & Heimer, 1978; Johnson et al., 2000), and extended to the piriform cortex, due to the physical proximity of the two structures, their interconnectivity (D. M. G. Johnson et al., 2000) and their essential involvement in odor transduction (see theoretical part).

Similar amygdalar activations were also obtained in response to aversive stimulation in study 1, as shown by its recruitment in clusters centered in the in the posterior piriform cortex and the PHG

178 (U>P, UF>H and UF>GEOS contrasts from study 1, Figure 55b, dark blue blobs), and could related to the contribution of centromedial amygdalar complexes to avoidance learning (Prévost et al., 2011).

Nevertheless, we failed to retrieve such an activation for all other unpleasant>pleasant comparisons in the other studies (U>P contrasts from preliminary study and study 2), which appears to be in line with the contradictory evidence regarding the role of amygdala in odor pleasantness processing discussed in the introduction (see section 2.4.4, theoretical part), and advocating for a role in intensity coding. The scarcity of unpleasant odors in comparison to pleasant ones (3 vs. 9 in study 1, compared to 2 vs. 2 in study 2), may have artificially enhanced the saliency of aversive smells, thus resulting in residual amygdala activation. Such confound should be taken into account for future experiments when manipulating odor valence, intensity and odor-borne arousal.

Interestingly, amygdala activation was also induced by desaturating scores measuring the subjective experience of relaxation (RX) in GEOS in study 1. This cluster was located more ventro-laterally than those elicited by odor detection and intensity (Figure 55b, pink and yellow blobs respectively), in the basolateral amygdala. The semantic descriptors of the relaxation category – Relaxed, Serene, Soothed – relate to calm, or a low state of arousal. Thus, this anti-correlation of basolateral amygdala activation with odor-induced relaxation could reflect the relation of amygdala to high emotional arousal, for reviews see Hamann, 2001, 2003; LaBar & Cabeza, 2006; Ledoux, 2000; Phan et al., 2003). At the physiological level, amygdalar lesions or electrical stimulation reportedly affect the generation of skin conductance response (Bechara et al., 1995; Bechara, Damasio, Damasio, & Lee, 1999; Mangina & Beuzeron-Mangina, 1996), which is an index of emotional arousal as mentioned in section 3.2 of the theoretical part. More particularly, research on memory processes has evidenced that the release of peripheral epinephrine and central norepinephrine through the locus coeruleus (LC) in response to stress or arousal, has an influence on memory consolidation, selectively mediated by adreno-receptors in the basolateral amygdala (Ferry et al., 2015; Galvez, Mesches, & McGaugh, 1996; Introini-Collison, Ford, & McGaugh, 1995; McGaugh, Cahill, & Roozendaal, 1996; McGaugh, Introini-Collison, & Nagahara, 1988; Quirarte, Galvez, Roozendaal, & McGaugh, 1998; Quirarte, Roozendaal, & McGaugh, 1997, for reviews see Ferry & Quirarte, 2012; McGaugh, 2000; McIntyre, McGaugh, & Williams, 2012).

Our data is consistent with this sensitivity to arousal / anti-relaxation in the basolateral amygdala, and calls for a more formal assessment of the relation between the relaxation category of EOS and physiological indices of arousal such as SCR or pupillary dilation. Moreover, the distinct dorsomedial vs. basolateral amygdala signatures obtained for odor intensity vs. arousal questions the abundant use of odor intensity as a proxy for the latter (Anderson, Christoff, Panitz, De Rosa, & Gabrieli, 2003;

Bensafi, Rouby, Farget, Bertrand, et al., 2002a; Winston et al., 2005). It would thus be interesting to

179 test whether odor arousal could be elicited independently of intensity, whether high odor intensity would necessarily induce an arousal response, and to disentangle their representation at the neural level, using high resolution fMRI and manual segmentation for a better localization of the signal within amygdala nuclei (Prévost, McCabe, Jessup, Bossaerts, & O’Doherty, 2011). Such an experiment could be done by manipulating the concentration (low, intermediate, high) of a selection of odorants, ranging from low to highly arousing (or high to low relaxing), obtained on the basis of subjective reports (Phan et al., 2003) or physiological measurements (Critchley, Elliott, Mathias, & Dolan, 2000).

Arousal could also be modified by manipulating the relevance of given odors, through selective satiation or associative learning as this has been done previously (see Li, Howard, Parrish, &

Gottfried, 2008; O’Doherty et al., 2000; Plailly et al., 2011; Small, Zatorre, Dagher, Evans, & Jones-Gotman, 2001). For instance, if would be possible to verify whether highly arousing odors would induce a differential pattern than low arousing odors – perhaps related to those reported in previous studies (Critchley et al., 2000; Lewis, Critchley, Rotshtein, & Dolan, 2007; Phan et al., 2003), and if odor intensity variations would result in the same pattern changes.

Figure 55. Coronal brain sections displaying differential activity in the amygdala related to the different paradigms used in this thesis work.

a) Amygdala activation related to odor detection, for the Odor>No Odor contrast in the prestudy (yellow blobs), the Odor>Sound localizer (red blobs) and the Odor + Sound>Sound control contrast (cyan blobs) in study, and the intensity related parametrical modulation in study 1 (I+, green blobs). The amygdala activation resulting from the Odor>No odor contrast in study 1 is not visible here, as it falls precisely within the overlap of all the other activation, represented in white. b) Comparative activation of amygdala in response to odor detection (all contrasts detailed in a), yellow blobs), odor intensity (I+ from study 1, green blobs), odor valence (Unpleasant>Pleasant odors contrast, from study 1, dark blue blob), and arousal (GEOS>Relaxation contrast from study 1, pink blob).

WB, p=0.001 unc, except for contrasts related to the prestudy, p=0.005, unc.

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