• Aucun résultat trouvé

Expectancy effects of pain and disgust in perceptual and moral decisions

N/A
N/A
Protected

Academic year: 2022

Partager "Expectancy effects of pain and disgust in perceptual and moral decisions"

Copied!
210
0
0

Texte intégral

(1)

Thesis

Reference

Expectancy effects of pain and disgust in perceptual and moral decisions

SHARVIT, Gil Shlomo

Abstract

Although expectancy effects have been described before (e.g. placebo effect), no one ever questioned their specificity. After all, it might be that when people anticipate pain, they form a representation of the approaching event, which could be shared with other aversive experiences, such as the case of disgust. In the present thesis, I examined the nature and specificity of expectancy of pain and disgust in the context of perceptual decisions (Experiments 1 & 2) and higher cognitive (moral) decisions (Experiments 3 & 4). I conducted four experiments to analyze behavioral, physiological and neural measures (using fMRI) from healthy human volunteers, which were all engaged in a new experimental set-up, specifically developed for testing the following experimental questions: (1) to which degree pain and disgust expectations recruit similar/dissociated representations of the upcoming event? (2) to which extent pain and disgust expectations affect high-level decisions, such as those involving morally-questionable behavior?

SHARVIT, Gil Shlomo. Expectancy effects of pain and disgust in perceptual and moral decisions. Thèse de doctorat : Univ. Genève et Lausanne, 2016, no. Neur. 188

PMID : PMC4668356

URN : urn:nbn:ch:unige-916245

DOI : 10.13097/archive-ouverte/unige:91624

Available at:

http://archive-ouverte.unige.ch/unige:91624

Disclaimer: layout of this document may differ from the published version.

1 / 1

(2)

UNIVERSITÉ DE GENÈVE FACULTÉ DE MÉDECINE

Département des Neurosciences Fondamentales Professeur Patrik Vuilleumier

FACULTÉ DE PSYCHOLOGIE ET DES SCIENCES DE L ÉDUCATION Département de psychologie Professeur Corrado Corradi-Dell'Acqua

Expectancy Effects of Pain and Disgust in Perceptual and Moral Decisions

THÈSE

présentée à la Faculté des sciences de l’Université de Genève pour obtenir le grade de Docteur ès sciences, mention Neurosciences

par Gil Sharvit

de

Hod Hasharon (Israël)

Thèse N°188

GENÈVE

Editeur ou imprimeur: Université de Genève

2016

(3)

Sharvit G, Vuilleumier P, Delplanque S, Corradi-Dell’ Acqua C. 2015. Cross-modal and modality-specific expectancy effects between pain and disgust. Sci Rep. 5:17487.

(4)

2

Remerciements

En premier lieu, je souhaite exprimer toute ma gratitude envers mes responsables: les Professeurs Patrick Vuilleumier et Corrado Corradi-Dell’Acqua pour leur soutien sans faille, leur patience, leurs encouragements et le partage de leur savoir tout au long de ce parcours.

Leurs conseils se sont avérés précieux non seulement pour l’aboutissement de ce projet mais également lors de la rédaction de ma thèse. Je n’aurais pu espérer meilleurs conseillers et mentors pour mon doctorat.

Je souhaite remercier les autres membres de l’examen oral: les Professeurs Tobias Brosch et Nicolas Silvestrini pour leurs commentaires judicieux, ainsi que leurs encouragements mais également pour leurs questions incisives et pointues qui m’ont incité à analyser mon travail de recherche selon de plus larges perspectives. De plus je souhaite remercier les membres du jury présents lors de la soutenance publique de ma thèse : les Professeurs David Sander et Giorgia Silani, ainsi que les Dr Nicolas Silvestrini et Chantal Berna Renella pour m’avoir fait l’honneur de leur présence ainsi que pour leur examen critique de mon travail.

Mes sincères remerciements vont aussi vers les personnes qui ont été des enseignants importants pour moi : les Dr Sylvain Delplanque et Dr Aline Pichon qui m’ont enseigné comment mener à bien des expérimentations avec un olfactomètre et comment analyser des données physiologiques.

Je remercie également le Dr Sebastien Rieger, le Dr Rémi Neveu, le Dr Christophe Mermoud et Monsieur Bruno Bonnet pour m’avoir expliqué et appris avec beaucoup d’humour comment réaliser un examen d’IRM.

De plus, je remercie Enru Lin et Arthur Montalto pour leur aide significative dans l’acquisition des données de ce projet.

Par ailleurs, je souhaite remercier tous mes compagnons de route dont je garderai un souvenir mémorable : Tomas, Kim, Kalia, Ewa, Giada, Lia, Mihai, Petra, Mohsen, Laura, Delphine, Judith, Emilie Q, Sasha, Wiebke, Ursula, Despina, Matalia, Inna, Maarten, Marcel, Marcin, Monika, Olga, Fabien, Claire, Raph, Swan, Claudia, Elena et Rashmi.

Je souhaite tout particulièrement remercier le Dr Tomas Ros pour ces discussions stimulantes tenues au détour d’une partie de billard ou au cours d’une soirée ainsi que pour tous les plaisirs et divertissements que nous avons partagé au cours de ces quatre dernières années.

Je remercie de même ma petite amie, Caroline Trocmé qui m’a soutenu dans les derniers moments.

Enfin, je souhaite remercier ma famille: mes parents et mon frère pour leur soutien indéfectible au cours de la rédaction de ma thèse et au cours de ma vie de façon plus générale.

(5)

3

Abstract in English

The inspiration for my thesis work comes from the desire to understand what happens when people expect unpleasant events, such as pain. In those situations, I wanted to know what type of information is taken into account while we anticipate, and how this information shapes our subjective experience when the expected event finally arrives.

Although expectancy effects have been described before (e.g. the placebo analgesia effect), it seems that no one ever questioned their specificity. After all, it might be that when people anticipate pain, they form a representation of the approaching event, which is similar to when they anticipate other aversive experiences, such as the case of disgust. In the present thesis, I decided to focus on pain and disgust as they are qualitatively different experiences, but they share also many crucial elements – from theoretical considerations, through biological and neural processing to their final effect on the behavior (see Introduction section). Therefore, I examined the nature and specificity of expectancy of pain and disgust in the context of perceptual decisions (Experiments 1 & 2) and higher cognitive (moral) decisions (Experiments 3 & 4). I conducted four experiments on healthy human volunteers, which were all engaged in a new experimental set-up, specifically developed for testing the following experimental questions: (1) to which degree pain and disgust expectations recruit similar/dissociated representations of the upcoming event? (2) to which extent pain and disgust expectations affect high- level decisions, such as those involving morally-questionable behavior?

The first two experiments were designed to investigate whether the expectation of pain and disgust recruit information related to the sensory-specific component of the stimulus or its affective consequences (shared across modalities). In Experiment 1, I measured behavioral and physiological responses, whereas in Experiment 2, I measured behavioral and neural signal through fMRI.

Participants saw cues predicting the unpleasantness (high/low) and the modality (pain/disgust) of upcoming thermal or olfactory stimulations of matched unpleasantness. In both experiments, I found that identical thermal stimuli were perceived as more unpleasant when preceded by cues threatening about high (as opposed to low) pain. A similar expectancy effect was found for olfactory disgust.

Critically, weaker (in Experiment 1) or absent (Experiment 2) expectancy effects were observed in the cross-modal conditions, when thermal stimuli were preceded by high-disgust cues or olfactory stimuli preceded by high-pain cues, thus suggesting modality-specific effects for each modality. In Experiment 1, I also found expectancy effects on autonomic arousal as measured by electrodermal activity, with larger skin conductance response when the same simulations were preceded by a high- unpleasantness (as opposed to low-) cue. In Experiment 2, consistently with the behavioral

(6)

4

observations, I found that the stimulus-induced neural activity in the right dorsal anterior insula and middle cingulate cortex was positively modulated by the expected unpleasantness of an event of the same modality. Concurrently, the activity of these regions was negatively modulated by the expected unpleasantness of an event of a different modality. Taken together, the data suggest that the right anterior insula and mid cingulate cortex are sensitive to both pain and disgust. However, this functional heterogeneity does not go at the expense of sensory-specificity, as both regions keep track of the sensory modality of unpleasant events and whether they match (or mismatch) with prior expectations.

The last two experiments were designed to test whether moral judgments could be modulated in a comparable or differential way by pain and disgust expectancy. I therefore modified the paradigm used in Experiments 1-2 so that between the presentation of a predictive cue and the subsequent occurrence of thermal/olfactory event, participant read a short story and evaluated the appropriateness of the protagonist’s conducts. This allowed me to test the effect of different expectation settings (pain, disgust, neutral event) on moral processing, but also the effect of the moral content of the story on the subsequent stimulations. In Experiment 3, I measured behavioral and physiological responses, whereas in Experiment 4, I measured behavioral and neural signal through fMRI. The behavioral results from both experiments revealed that expectancy of high disgust led to harsher judgments as opposed to either low disgust or high pain. I found instead no effects of the moral content of the story on the subjective evaluation of the subsequent stimulus, although in Experiment 3 the skin-conductance response elicited by high (relative to low) disgust was more pronounced following stories describing inappropriate (relative to appropriate) conducts. In Experiment 4, the analysis of brain activity associated with the moral processing revealed that the precuneus and posterior portions of the cingulate cortex were modulated by the moral content of the stories, but more when expecting high disgust (relative to low disgust or high pain). Furthermore, the analysis of brain activity in the piriform cortex elicited by high disgusting (relative to low disgusting) odors was more pronounced following stories describing inappropriate (relative to appropriate) conducts. Our results demonstrate that the representation triggered by disgust expectation could bias the judgment of other’s conducts, but also that the representation of inappropriate conducts could bias the physiological/neural responses of disgust. Our results go in line with previous embodiment theories, suggesting that moral disgust is grounded on physical disgust in a modality-specific manner, not shared by other aversive modalities such as pain.

Overall, our data of all experiments converge in arguing that expectation of pain and disgust can affect both perceptual and moral judgments in a modality-specific fashion, as revealed by the analysis of behavioral, physiological and neural signals.

(7)

5

Abstract in French

L’inspiration de mon travail de thèse vient du désir de comprendre ce qui arrive quand les gens s’attendent à des événements désagréables comme la douleur. Dans ces situations, j’ai voulu savoir quel type d’information est pris en compte quand on anticipe, et comment cette information influence notre expérience subjective quand l’événement attendu arrive enfin.

Même si les effets d’anticipation ont déjà été décrit (par exemple l’effet placebo analgésique), il semblerait que personne n’a questionné sa spécificité auparavant. Après tout, il est possible que quand les gens anticipent la douleur, ils créent une représentation de cet événement qui se rapproche, représentation qui est similaire à quand ils anticipent d’autres expériences aversives, comme dans le cas du dégoût. Dans cette thèse, j’ai décidé de me focaliser sur la douleur et le dégoût car ils sont des expériences qualitativement différentes, mais ils partagent aussi beaucoup d’éléments cruciaux – des considérations théoriques, à travers les traitements biologiques et neuraux à leur effet final sur le comportement (voir la section Introduction). Ainsi, j’ai examiné la nature et la spécificité de l’anticipation de la douleur et du dégoût dans le contexte des décisions perceptuelles (Expériences 1&2) et des décisions (morales) de haut niveau cognitif. J’ai conduit quatre expériences sur des volontaires sains humains, qui étaient tous engagés dans un dans une nouvelle installation expérimentale, développée spécifiquement pour tester les questions expérimentales suivantes : (1) à quel point l’anticipation de douleur et du dégoût recrutent des représentations similaires/dissociées de l’événement à venir ? (2) dans quelle mesure l’anticipation de la douleur et du dégoût affecte des décisions de haut niveau, telles que celles impliquées dans un comportement questionnable moralement ?

Les deux premières expériences ont été conçues pour investiguer si l’anticipation de la douleur et du dégoût recrute l’information liée au composant sensoriel spécifique du stimulus ou à ses conséquences affectives (partagées à travers les modalités). Dans l’Expérience 1, j’ai mesuré les réponses comportementales et physiologiques, alors que dans l’Expérience 2, j’ai mesuré le signal comportemental et neural par l’IRMf. Les participants ont vu des indices prédisant le caractère désagréable (haut/bas niveau) et la modalité (douleur/dégoût) des stimulations thermiques et olfactives de caractère désagréable correspondant. Dans les deux expériences, j’ai trouvé que les stimuli thermiques étaient perçues comme plus désagréables quand elles étaient précédées d’indices menaçant de haut niveau (plutôt que bas niveau) de douleur. Un effet d’anticipation a été trouvé pour le dégoût olfactif. De manière cruciale, des effets d’attente plus faibles (dans l’Expérience 1) ou absentes (Expérience 2) ont été observées dans les conditions inter-modales, quand les stimuli

(8)

6

thermiques ont été précédés par des indices de haut niveau de dégoût ou des stimuli olfactifs précédés par des indices de haut niveau de douleur, suggérant par conséquent des effets spécifiques à la modalité pour chaque modalité. Dans l’Expérience 1, j’ai aussi trouvé des effets d’anticipation sur l’excitation du système nerveux autonome mesuré par l’activité électrodermale, avec une plus grande réponse de la conductance de la peau quand les mêmes simulations ont été précédées par un indice de haut niveau de caractère désagréable (plutôt que bas niveau). Dans l’Expérience 2, de manière cohérente avec les observations comportementales, j’ai trouvé que l’activité neurale induite par les stimuli dans l’insula droite dorsale antérieure et le cortex cingulaire moyen était positivement modulée par l’anticipation du caractère désagréable d’un événement de la même modalité.

Simultanément, l’activité dans ces régions était négativement modulée par l’anticipation du caractère désagréable d’un événement d’une modalité différente. Pris ensemble, ces données suggèrent que l’insula droite antérieure et le cortex cingulaire moyen sont sensibles à la fois à la douleur et au dégoût.

Cependant, ces hétérogénéités ne vont pas aux dépens de la spécificité sensorielle, puisque les deux régions gardent la modalité sensorielle des événements à caractère désagréable et si elles sont en accord (ou en désaccord) avec les anticipations précédentes.

Les deux dernières expériences ont été conçues pour tester si les jugements moraux peuvent être modulés d’une façon comparable ou différente par l’anticipation de la douleur et du dégoût. J’ai donc modifié le paradigme utilisé dans les Expériences 1-2 de telle sorte qu’entre la présentation d’un indice prédictif et l’occurrence ultérieure d’un événement thermal/olfactif, le participant lisait une courte histoire et évaluait le caractère approprié des conduites du protagoniste. Cela m’a permis de tester l’effet de différents cadres d’anticipation (douleur, dégoût, événement neutre) sur le traitement moral, mais aussi l’effet d’un contenu moral de l’histoire sur les stimulations ultérieures. Dans l’Expérience 3, j’ai mesuré les réponses comportementales et physiologiques, alors que dans l’Expérience 4, j’ai mesuré le signal comportemental et neural par l’IRMf. Les résultats des deux expériences ont révélé que l’anticipation d’un haut niveau de dégoût conduisait à des jugements plus sévères contrairement à un bas niveau de dégoût ou haut niveau de douleur). De plus, les analyses de l’activité du cerveau dans le cortex piriforme provoqué par des odeurs de haut niveau de dégoût (par rapport à bas niveau de dégoût) était plus prononcé après des histoires décrivant des conduites inappropriées (par rapport à appropriées). Nos résultats démontrent que la représentation déclenchées par l’anticipation du dégoût pourrait biaiser le jugement des conduites d’autrui, mais aussi que la représentation des conduites inappropriées pourrait biaiser les réponses physiologiques/neurales du dégoût. Nos résultats s’alignent avec les théories précédentes de l’incarnation, suggérant que le dégoût moral est basé sur le dégoût physique de manière spécifique à la modalité, mais pas partagé par les autres modalités repoussantes telles que la douleur. Dans

(9)

7

l’ensemble, nos données de toutes les expériences convergent dans le sens que l’anticipation de la douleur et du dégoût peut affecter à la fois les jugements perceptuels et moraux d’une façon spécifique à la modalité, comme les analyses des signaux comportementaux, physiologiques et neuraux le révèlent.

(10)

8

List of Abbreviations

ACC: Anterior Cingulate Cortex AI: Anterior Insula

aMCC: anterior Middle Cingulate Cortex Amyg: Amygdala

ANCOVA: Analysis of Covariance ANOVA: Analysis of Variance AON: anterior Olfactory Nucleus APC: anterior Piriform Cortex

BOLD: Blood-oxygenation-level Dependent BPM: Bit Per Minute

CCK: Cholecystokinin cHD: High Disgust Cue cHP: High Pain Cue

CL: Central Lateral Nuclues cLD: Low Disgust Cue cLP: Low Pain Cue

CNS: Central Nervous System dAI: dorsal Anterior Insula dl: dorsolateral

DLPFC: Dorsolateral Prefrontal Cortex DMPFC: Dorsomedial Prefrontal Cortex EDA: Electrodermal Activity

Ex-: Experiment- Exp.: Expiration

FIR: Finite Impulse Response

fMRI: functional Magnetic Resonance Imaging FWE: Family-wise Error

GLM: General Linear Model GSR: Galvanic Skin Response HD: High Disgust Stimulation HP: High Pain Stimulation HR: Heart Rate

HRF: Hemodynamic Response Function HT: High Threshold

IFG: Inferior Frontal Gyrus Ins.: Inspiration

ISI: Inter Stimulus Interval ITG: Inferior Temporal Gyrus lAI: Left Anterior Insula LD: Low Disgust Stimulation LOT: Lateral Olfactory Tract LP: High Pain Stimulation LT: Low Threshold

MCC: Middle Cingulate Cortex MDvc: Medial Dorsal Nucleus MFG: Middle Frontal Gyrus MI: Middle Insula

MPFC: Medial Prefrontal Cortex MTG: Middle Temporal Gyrus MVPA: Multi-Voxel Pattern Analysis n.s.: nonsignificant

NS: Nociceptive OB: Olfactory Bulb OFC: Orbitofrontal Cortex

OSNs: Olfactory Sensory Neurons OTUB: Olfactory Tubercle

pACC: posterior Anterior Cingulate Cortex PAG: Periaqueductal Gray

PAG-RVM: The Periaqueductal Gray – Rostral Ventromedial Medulla System

PB: Parabrachial Nucleus PC: Precuneus

PCC: Posterior Cingulate Cortex PET: Positron Emission Tomography

(11)

9 Pf: Parafascicular Nucleus

PFC: Prefrontal Cortex PI: Posterior Insula PirC: Piriform Cortex

pMCC: posterior Middle Cingulate Cortex rAI: right Anterior Insula

RVM: Rostral Ventromedial Medulla s: second

S1: Primary Somatosensory Cortex S2: Secondary Somatosensory Cortex SCRs: Skin Conductance Response SFG: Superior Frontal Gyrus

SI / Supp.: Supplementary Information SMA: Supplementary Motor Area SNR: Signal-to-noise Ratio SPL: Superior Parietal Lobule

SPM: Statistical Parametric Mapping SRD: Subnucleus Reticularis Dorsalis STG: Superior Temporal Gyrus

STS: Superior Temporal Sulcus STT: Spinothalamic Tract TE: Echo Time

TPJ: Temporoparietal Junction TR: Repetition Time

Unp. Unpleasantness VI: Ventral Insula

VL: Ventral Lateral Nucleus vm: ventromedial

VMb: Ventrobasal Thalamus

VMPFC Ventromedial Prefrontal Cortex VMpo: Ventral Medial Nucleus

VP: Ventral Posterior Nuclues

VPM: Ventral Posterior Medial Nuclues WDR: Wide Dynamic Range

(12)

10

Table of Contents

Acknowledgements ... 2

Abstract in English ... 3

Abstract in French ... 5

List of Abbreviations ... 8

Table of Contents ... 10

List of Figures ... 14

List of Tables ... 16

Theoretical Part ... 17

1 Abstract of Literature Review ... 18

2 Literature Review ... 20

2.1 The Evolution of Pain & Disgust theories ... 20

2.1.1 History of pain ... 20

2.1.2 History of disgust ... 29

2.2 The Perception of Pain & Disgust ... 34

2.2.1 Sensory pathways of pain ... 34

2.2.2 Sensory pathways of disgust ... 42

2.3 Cognitive & Affective Modulation of Pain & Disgust ... 48

2.3.1 Expectations ... 48

2.3.2 Attentional and emotional influences ... 52

2.3.3 Confounds between expectation, attention, and emotion ... 56

2.4 Moral Cognition & Disgust ... 58

2.4.1 Theories of moral cognition and their treatment to moral emotions ... 58

2.4.2 The link between moral and physical disgust ... 61

3 Thesis Objectives ... 63

3.1 Research Question 1 ... 64

3.2 Research Question 2 ... 65

3.3 Quantitative comparison between Pain and Disgust ... 65

(13)

11

Experimental Part ... 68

1 Chapter 1 ... 69

1.1 Abstract ... 69

1.2 Introduction ... 69

1.3 Materials & Methods ... 72

1.3.1 Participants ... 72

1.3.2 Olfactory stimulation ... 72

1.3.3 Thermal stimulation ... 73

1.3.4 Main Experimental Setup ... 73

1.3.5 Physiological recordings ... 75

1.4 Results ... 76

1.4.1 Behavioral Ratings ... 76

1.4.2 Physiological measures ... 81

1.4.3 Emotional response to the cue ... 83

1.5 Interim Discussion ... 85

1.5.1 Limitations of the study ... 85

1.6 Supplementary Information... 86

1.6.1 Preselection of odorants ... 86

1.6.2 Preselection of thermal stimuli ... 86

1.6.3 Analysis of physiological responses during the expectations period ... 87

2 Chapter 2 ... 88

2.1 Abstract ... 88

2.2 Introduction ... 88

2.3 Materials & Methods ... 90

2.3.1 Participants ... 90

2.3.2 Olfactory stimulation ... 90

2.3.3 Thermal stimulation ... 91

2.3.4 Experimental Setup ... 92

2.3.5 Physiological recordings ... 95

2.3.6 Imaging processing... 95

2.4 Results ... 97

2.4.1 Behavioral Results ... 97

2.4.2 Respiration measure ... 99

2.4.3 Neural Activity ... 100

2.5 Interim Discussion ... 107

(14)

12

2.5.1 Limitations of the study ... 107

2.6 Supplementary Information... 108

2.6.1 Supplementary Results ... 108

2.6.2 Supplementary Figures ... 109

2.6.3 Supplementary Tables... 110

3 Chapter 3 ... 114

3.1 Abstract ... 115

3.2 Introduction ... 116

3.3 Materials & Methods ... 118

3.3.1 Participants ... 118

3.3.2 Olfactory stimulation ... 118

3.3.3 Thermal stimulation ... 119

3.3.4 Dilemmas ... 120

3.3.5 Experimental Setup ... 121

3.3.6 Physiological measures ... 124

3.3.7 Imaging processing... 126

3.4 Results ... 127

3.4.1 Behavioral Responses ... 128

3.4.2 Physiological Responses ... 131

3.4.3 Neural Responses ... 135

3.5 Interim Discussion ... 141

3.5.1 Limitations of the study ... 141

3.6 Supplementary information ... 143

3.6.1 Supplementary Results ... 143

3.6.2 Supplementary Figures ... 144

3.6.3 Supplementary Tables... 148

4 General Discussion ... 149

4.1 Common and dissociated responses to pain and disgust. ... 151

4.1.1 Physiological Responses ... 151

4.1.2 Neural responses ... 152

4.2 Expectancy of Pain and Disgust on perceptual decisions ... 153

4.2.1 Behavioral Responses ... 153

4.2.2 Neural Responses in Insula and MCC ... 154

4.2.3 Attention allocation and modality-switch ... 156

4.3 Expectancy of Pain and Disgust on moral decision ... 157

4.3.1 From expectancy paradigms to embodied accounts ... 157

(15)

13

4.3.2 Disgust expectancy biases moral processing ... 158

4.3.3 Inappropriate behavior biases disgusting experience ... 160

5 Thesis Conclusions ... 161

6 References ... 162

(16)

14

List of Figures

FIGURE 1- DESCARTES' PAIN PATHWAY. ... 22

FIGURE 2- MELZACK AND WALLS GATE CONTROL THEORY OF PAIN. ... 25

FIGURE 3- NEUROSYNTH TERM-BASED META-ANALYSES OF PAIN. ... 26

FIGURE 4 OVERLAPPING NEURAL ACTIVITY BETWEEN PAIN & DISGUST. ... 28

FIGURE 5 THE TWO MAIN ASCENDING PATHWAYS OF PAIN. ... 38

FIGURE 6- THE PAG-RVM DESCENDING MODULATORY SYSTEM... 42

FIGURE 7 THE GUSTATORY SYSTEM. ... 44

FIGURE 8 THE OLFACTORY SYSTEM. ... 46

FIGURE 9- THE DUAL PROCESS THEORY OF MORAL JUDGEMENT. ... 60

FIGURE 10 THE EVENT-FEATURE-EMOTION COMPLEX (EFEC) FRAMEWORK... 61

FIGURE 11 TASK OF EXPERIMENT 1. ... 71

FIGURE 12- UNPLEASANTNESS RATINGS OF THERMAL AND OLFACTORY STIMULI AS A FUNCTION OF THE PREDICTIVE CUES. ... 78

FIGURE 13- INFLUENCE OF CONSCIOUS RELIANCE ON THE CUE ON THE STRENGTH OF MODALITY-SPECIFIC EXPECTANCY EFFECTS. ... 80

FIGURE 14- EVENT-RELATED PHYSIOLOGICAL RESPONSES DURING REFERENCE TRIALS. ... 82

FIGURE 15 MEAN VALUES OF THE PHYSIOLOGICAL MEASURES ACROSS ALL EXPERIMENTAL CONDITIONS. ... 83

FIGURE 16- EMOTIONAL RESPONSE TO THE DIFFERENT CUES COLLECTED BEFORE AND AFTER THE EXPERIMENTAL SESSION. ... 84

FIGURE 17 TASK OF EXPERIMENT 2. ... 94

FIGURE 18- UNPLEASANTNESS RATINGS FOR THERMAL AND OLFACTORY STIMULI AS A FUNCTION OF THE PREDICTIVE CUES. ... 98

FIGURE 19- EVENT-RELATED RESPIRATORY RESPONSE DURING REFERENCE TRIALS. ... 100

FIGURE 20- NEURAL STRUCTURES ASSOCIATED WITH MODALITY-SPECIFIC AND MODALITY-SHARED ACTIVATIONS DURING REFERENCE TRIALS... 101

FIGURE 21- NEURAL STRUCTURES THAT ARE MODULATED BY CONSISTENT AND INCONSISTENT EXPECTATIONS (STIMULUS MODALITY X CUE MODALITY INTERACTION) DURING MEDIUM TRIALS. ... 103

FIGURE 22- NEURAL STRUCTURES IDENTIFIED BY THE 3-WAY (STIMULUS MODALITY X CUE MODALITY X CUE UNPLEASANTNESS) INTERACTION DURING MEDIUM TRIALS. ... 106

FIGURE 23 SUPP. NEURAL ACTIVITY ASSOCIATED WITH PAIN AND DISGUST DURING REFERENCE TRIALS. ... 109

FIGURE 24 TASK OF EXPERIMENTS 3-4. ... 123

FIGURE 25- APPROPRIATENESS RATINGS FOR DILEMMAS AS A FUNCTION OF THE PREDICTIVE CUES (EXP.3-4). ... 129

FIGURE 26- UNPLEASANTNESS RATINGS FOR THERMAL AND OLFACTORY STIMULI FOLLOWING DILEMMAS AS A FUNCTION OF THE PREDICTIVE CUES (EXP.3-4). ... 131

FIGURE 27 ELECTRODERMAL ACTIVITY OF STIMULATION EPOCHS FOLLOWING DILEMMAS (EXP.3). ... 133

FIGURE 28- HEART RATE AND RESPIRATION PATTERN OF STIMULATION EPOCHS FOLLOWING DILEMMAS (EXP.3-4). ... 135

FIGURE 29 NEURAL STRUCTURES WHOSE ACTIVITY IS PARAMETRICALLY MODULATED BY THE DILEMMAS APPROPRIATENESS, SEPARATELY FOR DILEMMA READING AND RATING EPOCHS (EX-4). ... 137

(17)

15

FIGURE 30 NEURAL STRUCTURES WHOSE ACTIVITY IS PARAMETRICALLY MODULATED BY THE DILEMMAS APPROPRIATENESS DURING DILEMMA READING EPOCHS, WHEN EXPECTING HIGH DISGUST AS OPPOSED TO HIGH PAIN (EX-4). ... 139 FIGURE 31- NEURAL RESPONSES TO DISGUST STIMULATIONS FOLLOWING DILEMMAS IN THE RIGHT PIRIFORM CORTEX (EX-4). ... 140 FIGURE 32- SUPP. RATINGS OF APPROPRIATENESS, EMOTIONAL ENGAGEMENT, AND COMPREHENSION OF THE 32 DILEMMAS THAT

WERE USED IN THE MAIN EXPERIMENT FOLLOWING AN ONLINE PILOT STUDY. ... 144 FIGURE 33- SUPP. UNPLEASANTNESS RATINGS FOR THERMAL AND OLFACTORY STIMULI OF THE REFERENCE TRIALS AS A FUNCTION OF

THE PREDICTIVE CUES (EXP.3-4). ... 144 FIGURE 34- SUPP. PHYSIOLOGICAL RESPONSES ASSOCIATED WITH DILEMMA READING AND RATING EPOCHS. ... 145 FIGURE 35- SUPP. PHYSIOLOGICAL RESPONSES ASSOCIATED WITH THERMAL AND OLFACTORY STIMULI OF THE REFERENCE TRIALS. . 146 FIGURE 36 SUPP. NEURAL RESPONSES TO PAIN STIMULATIONS FOLLOWING DILEMMAS, REGARDLESS OF THE PRECEDING DILEMMA.

... 147 FIGURE 37- SUPP. NEURAL RESPONSES TO PAIN AND DISGUST STIMULATIONS OF THE REFERENCE TRIALS. ... 147

(18)

16

List of Tables

TABLE 1- SHARED FEATURES BETWEEN PAIN & DISGUST. ... 63 TABLE 2- UNPLEASANTNESS RATINGS, SCR, HR AND INSPIRATION VOLUME ASSOCIATED WITH EACH EXPERIMENTAL CONDITION. ... 79 TABLE 3 CLUSTERS OF MODALITY-SPECIFIC AND MODALITY-SHARED ACTIVATIONS ASSOCIATED WITH STIMULATIONS OF REFERENCE

TRIALS... 102 TABLE 4 CLUSTERS OF ACTIVATION ASSOCIATED WITH INTERACTION TERMS OF MEDIUM TRIALS. ... 104 TABLE 5 SUPP. CLUSTERS OF ACTIVATION ASSOCIATED WITH PAIN AND DISGUST STIMULATIONS OF REFERENCE TRIALS. ... 110 TABLE 6- SUPP. CLUSTERS OF ACTIVATION ASSOCIATED WITH MAIN EFFECTS OF STIMULUS MODALITY AND CUE UNPLEASANTNESS OF

MEDIUM TRIALS, AND WITH CONSISTENT > INCONSISTENT ACTIVATIONS OF DISGUST-SPECIFIC MEDIUM TRIALS. ... 111 TABLE 7- CLUSTERS OF ACTIVATION ASSOCIATED WITH [INAPPROPRIATE OR APPROPRIATE] DILEMMA READING AND RATING EPOCHS.

... 138 TABLE 8- SUPP. CLUSTERS OF ACTIVATION ASSOCIATED WITH PAIN STIMULATIONS FOLLOWING DILEMMAS. ... 148

(19)

17

Theoretical Part

(20)

18

1 Abstract of Literature Review

Pain and disgust are both aversive somatic experiences that people try to avoid in daily situations.

Apart from being unpleasant when encountered, at first sight, it seems that pain and disgust are two distinct experiences, which were analyzed mostly in a domain-specific manner. However, a closer inspection into the literature reveals a different picture. In the first three sections (Sections 2.1-2.3), I review the theories (Section 2.1), the sensory processing (Section 2.2), and the modulating factors (Section 2.3) of pain and disgust, and provide evidence for many shared (as well as distinct) features between the two modalities. In the last section (Section 2.4), I examine the link between disgust and morality by reviewing theories of moral cognition, together with recent experimental findings.

With its first academic discussions going back to ancient Greece, the perspective on pain has changed many times through history, from those who considered it an emotion, or an imbalance in vital fluids, to more recent accounts, as a multi-dimension experience with sensory and affective aspects (Section 2.1.1). In comparison, the discussion about disgust has only started in the early modern period:

although all theories converge in defining this experience as an emotion evolved from distaste, they all also highlight its multi-componential nature, with different models suggesting different subdivisions (Section 2.1.2). Indeed, it has been proposed that, in addition to the physical experience of disgust grounded in the sensory (in particular chemosensory) system, individuals might experience a different class of disgust, of “moral” flavor, when socially-unacceptable rules of conduct are detected (Section 2.4). In particular, embodied theories of moral cognition propose that physical (e.g.

chemosensory) and moral disgust might rely on shared processing systems.

Although pain and disgust have been considered qualitatively different experiences and were investigated by independent lines of research, their processing shares several features. First, it has been argued that both pain (Section 2.2.1) and disgust (Section 2.2.2) can be elicited by a wide range of sources (e.g., audition, somatosensation, and olfaction) including those of “social” nature (e.g., unfair treatments can elicit either social pain or moral disgust). Second, in some instances, their ascending neural pathways are shared (facial pain is in part processed by trigeminal tract which also processes unpleasant irritant odors). Third, at the cortical level a similar brain network, comprehending the insular and cingulate cortex, have been hypothesized to underlie the primary experience of both pain and disgust. Finally, both of these experiences can be modulated in a similar manner by expectations (Section 2.3.1), as well as by attention and emotion (Section 2.3.2), and. These modulations have been demonstrated extensively for pain and, in smaller extent, also for disgust.

(21)

19

Overall, it is possible that, due to the multi-componential nature of both these experiences, pain and disgust might share one or more processing levels, as suggested by recent neuroimaging models about insular and cingulate’s function. Expectation paradigms might be an incredibly powerful tool to establish whether and to which extent this is the case.

(22)

20

2 Literature Review

2.1 The Evolution of Pain & Disgust theories

In this section I provide a review of the theoretical advances in the research of pain (Section 2.1.1) and disgust (Section 2.1.2). This includes discussion over definitions, description of theoretical and empirical models, and landmark discoveries that led to a change in perspective.

2.1.1 History of pain

From a historical perspective, the view on pain has changed throughout the years as a result of significant advances in research methodologies. Many attempts have been made to define pain; while philosophers provided the first abstract concepts through pondering, scientists have constructed empirical theories by integrating available knowledge at that time. As a result, these attempts produced a variety of theoretical and functional definitions for pain, suggesting the difficulty in defining this complex phenomenon.

Pain is considered the oldest medical problem and the universal physical affliction of mankind1. Therefore, it is not surprising that the first contemplation of pain can be tracked all the way back to Ancient Greece, where the understanding of pain and its treatment occupied many poets, tragedians, and philosophers.

The oldest written information on pain can be found in the epic mythological poems by Homer (~850 BC) in which pain was related to emotion. In his poems, Homer referred to pain as a state of mind consisting an emotional suffering2. “Pain” (or “Ponos” in Greek) was used as a synonym to “Algos” and

“Odyni”, which were used to point the torture of man as a result of war or injury throughout the long way journey of returning2. Most of the heroes in Greek mythology were not only trained in battle but also in healing practice, where herbal substances such as Nepenthes, or opium, were often used for emotional pain relief3.

For the Greek philosophers, pain was used to be a phenomenon that should be defined by pondering over its nature (what is pain?), cause (why people are in pain?), origin (what is the center of pain), and purpose (what is the utility of pain?). The first who contemplated about the concept of pain were Pythagoras (570-495 BC) and Antiphon (500 BC). Interestingly, to realize what pain was, they had to contrast it with pleasure. Pythagoras have argued that pleasure is a goal of which men voluntarily pursue to reach harmony with their souls, while pain is an involuntary disruption to the souls’

harmony4. Similarly, Antiphon stated that for humans to achieve great pleasure, pain should be eliminated. Following his realization, Antiphon developed a method to treat pain through conversation, which later considered to be the first precursor of modern psychotherapy5.

(23)

21

Years later, Hippocrates (460-370 BC), a philosopher and the first doctor who separated religion from sickness (by searching for the physical causes of diseases)3, suggested a more mechanistic view.

According to which, pain reflects an imbalance in the four vital fluids of the body (blood, phlegm, yellow and black bile)6. For the first time, pain was considered a symptom that can be treated by men (and not by Gods). This consideration paved the way for new therapies that were grounded on physical substances (herbal medicine, chemical mixtures, and special diets), rather than on religious elements (pray, rituals).

Remarkably, Hippocrates’ view did not prevail for long. The succeeding philosopher, Plato (428-348 BC), decided to follow the previous approach of Pythagoras and Antiphon, and so, he contrasted pain with pleasure in his book “Passions of the Soul”. Plato, however, did not consider pain and pleasure as motivational goals (as Pythagoras and Antiphon did), but as different emotions.

Consistent with Plato, Aristotle (384-322 BC) also claimed that pain is an emotion. Though, Aristotle added that pain enters the body via injury, which is caused by evil spirits and Gods. According to this Aristotelian perception, since pain upsets and destroys the nature of the person who feels it7, the heart is the central pain organ. Centuries later, Galen (AD 130–201), the leading physician of Alexandria, disagreed with Aristotle’s view. Through observations made in his clinical experience, Galen claimed that the brain should be the central organ for all feeling senses, including pain8. Another opposition to the Aristotelian perception came hundreds of years later. Avicenna (AD 980–1037), a renowned Muslim philosopher and physician, noted that pain could be dissociated from touch or temperature recognition, and proposed pain to be an independent sensation9.

Even though not all ancient philosophers accepted the Aristotelian perception, its influence on philosophical thought had an enduring impact that persisted throughout the Middle Ages. As a result, in the period between the Middle Ages and the scientific Renaissance in Europe, the prevailing view on pain was shaped by religious beliefs. Pain was considered as something that enters the body from the outside, serving either as a punishment from God or as a test to reaffirm the person’s faith1. Clearly, the heart was still regarded as the central pain organ.

Finally, the Aristotelian perception has come to an end during the Scientific Renaissance in Europe (1500-1700), where pain has been transformed from a spiritual, mystical experience to a physical, mechanical sensation that could be investigated by research. In this period, much of the attention was focused on the anatomy of the nervous system. As a result, this period concluded with the consensus of the brain as the central organ for pain perception.

(24)

22

One of the major landmarks of the Scientific Renaissance occurred in 1664 when Descartes’

formulated the first description of the pain system10. It was also one of the first detailed descriptions of the somatosensory pathway in humans. Descartes described pain as a perception that exists in the brain and further distinguished between the neural phenomenon of sensory transduction and the subjective experience of pain. In his description, (Figure 1), the nerves are regarded as hollow tubes (“fine thread”) that convey both sensory and motor information. Ultimately, this information leads to a perceptual experience (feeling pain), and to an appropriate, consequent behavior (e.g. to move away from a source of pain).

Even though Descartes provided a detailed mechanistic description of the pain system; he did not offer a solid dissociation between the spirit and the physical, as he also designated “animal spirits” to flow from the brain to the muscles to control behavior. Such dissociation had only occurred later when Newton and Hartley proposed neuronal messages to be vibrations of substance in nerves11. In sum, these two landmarks have provided a crucial framework for modern theories of pain, leading to a new era of empirical investigation.

Figure 1 - Descartes' pain pathway.

"Particles of heat" activate a spot of skin attached by a fine thread to a valve in the brain where this activity opens the valve, allowing the animal spirits to flow from a cavity into the muscles causing them to move away from the stimulus.

Taken from12.

Following the Scientific Renaissance, in the early modern period, pain researchers have conducted experiments to investigate how pain is transmitted from the periphery to the spinal cord and brain.

For instance, in 1858, Schiff demonstrated that particular lesions of the spinal cord resulted in the separate and independent loss of tactile and pain-related reactions13. Schiff reached the same conclusion that was offered a millennium earlier by Avicenna in which pain is an independent sensation. While Schiff’s view was popular at that time, it was not accepted by all. Based on

(25)

23

experiments performed by Naunyn in 185914, and on observations in which intense sensations are usually disagreeable and involve strong stimuli, Erb proposed in 1874 an alternative to Schiff’s conclusion - the Intensity Theory15, which is also considered to be the first explicit theory of pain.

According to the Intensity Theory, pain is not a unique sensory experience but rather a non-specific sensation that occurs when a stimulus is stronger (more intense) than usual15. Therefore, the theory suggests that there are no distinct pathways for non-noxious and noxious stimuli. Instead, a stimulus generates a certain number of impulses in neurons, which will determine its intensity. Furthermore, the Intensity Theory also portraited a signal-processing pathway; where the primary afferent neurons synapse onto second-order neurons (in the dorsal horn of the spinal cord), which encode low levels of activity as innocuous stimuli, and higher levels of activity as noxious stimuli.

Then, in 1884, two separate studies16,17 indicated how separate skin spots, when stimulated mechanically with small probes, could produce different sensory experiences (e.g. pressure, cold, warmth, pain). This finding was also supported by a series of histological experiments, conducted by von Frey between 1894 and 1897. From these experiments, Von Frey deduced a relationship between the stimulated skin spots and the structurally defined neural endings18–21, which eventually led to the formation of the Specificity Theory. In complete contrast to the Intensity Theory, the Specificity Theory22 suggests the presence of dedicated components for each somatosensory modality. These components consist of a receptor, a sensory fiber (primary afferent), and a pathway, all of which are sensitive and dedicated to conveying one specific stimulus23. The theory defines pain as a unique sensation, which has specific peripheral sensory receptors that react to damage and send signals through pain-specific pathways to the brain; then, dedicated pain centers in the brain process those signals to produce the painful experience.

Evidence supporting the Specificity Theory came only later. Following a series of neurophysiological experiments, Sherrington concluded in 1906 that the main function of a receptor is to lower the excitability threshold for one kind of stimulus and to heighten it for all others24–26. This conclusion for a “selection” approach provided the biological framework (i.e., the existence of pain-specific receptors) for the Specificity Theory. Remarkably, Sherrington’s explanation has also accounted those findings supporting the Intensity Theory, as it recognized the existence of an excitability threshold.

Moreover, during his studies Sherrington suggested to label a stimulus capable of tissue damage as

‘noxious’26, and also to describe the specificity of the cutaneous end-organ (i.e. receptor) for noxious stimuli as “nociceptor”27 (which is used until today). Furthermore, in 1926, Adrian and Zotterman showed that peripheral tissue stimulation, with different natural triggers (e.g. brushing/stroking, temperature changes, muscle stretch), can evoke a series of neuronal discharges from individual nerve

(26)

24

fibers28. These results were interpreted as stimulus-selective responses of nerve fibers, which were consistent with the Specificity Theory.

However, Adrian and Zotterman’s interpretation was not accepted by all, and so in 1929, Nafe offered an alternative explanation, which was later known as the Pattern Theory29. Nafe claimed that all peripheral sensations are produced by spatial and temporal patterns of neural firing, and not by separate modality-specific afferents29 (as suggested by Adrian and Zotterman28). According to Nafe’s Pattern Theory29, there is no separate system for perceiving pain, and the receptors for pain are shared with other senses, such as those of touch. Although the theory ignored previous observations supporting the Intensity or the Specificity Theories (threshold-dependent afferents, specialized nerve endings), it was reinforced by several stimulation studies. These studies demonstrated that nerve- fiber stimulation could trigger a wide range of sensory experiences (e.g. touch, cold, warm, prick, itch, and sharp pain), depending on the pattern of stimulation (and not on modality-specific nerve endings).30,31.

By 1930, there were three main theories of pain: Intensity Theory, Specificity Theory, and Pattern Theory, each with its supporting evidence. Notably, all these theories have tried to explain pain as a peripheral sensory experience. Yet, in 1943 Livingston31 (and later Hebb in 194932) decided to revive an old concept (taken from Plato), and proposed a theory (here labeled Motivational-Affective Theory) in which pain (and pleasure) is considered as a subjective motivational state (termed “appetites”) of behavior. Moreover, the theory also posited that pain is arises from activation of aversive networks in the brain. Livingston’s theory brought back the concept of early philosophers into the modern scientific discussion, which eventually caused a dramatic shift in thought about pain, as can be seen in later theories.

So far, the early modern theories of pain (i.e. Intensity Theory, Specificity Theory, Pattern Theory, and Motivational-Affective Theory) were considerably limited. These theories could not explain a broad range of experimental and clinical observations at that time (e.g. variable relationship between injury and reported pain, non-noxious stimuli leading to pain, persisting of pain after tissue healing, temporal changes in the nature and the location of pain, etc.)33. Most importantly, these early models were unable to provide efficient model-based treatments for patients in pain. The failure of these sensory and affective models to explain much of what was observed experimentally and clinically, have boosted the motivation to search for a more integrative model.

And so, in 1965, Melzack and Wall proposed the Gate Control Theory34, an idea that would become one of the most influential theories of pain research. The theory postulates nociception to be "gated"

by non-nociceptive signals through interneurons within the spinal cord. According to the theory,

(27)

25

specialized nociceptors and dedicated central pathways do not exist, instead the spectrum of primary afferent neurons has a range of thresholds in which the interplay between small nerve-fibers (Aδ and C) and large nerve-fibers (Aβ) determines the transmission of pain signals to the brain. Specifically, large-fiber activity inhibits (or closes) the gate, whereas small-fiber activity facilitates (or opens) the gate (Figure 2). When nociceptive information reaches a threshold that exceeds the inhibition elicited, it opens the gate, allowing the projection neurons to send the information through the dorsal column to the brain, resulting in the experience of pain (Figure 2). For instance, the theory could explain why rubbing a bumped knee could alleviate the resulting pain. Furthermore, the theory also proposed that the brain could modulate the gate via descending fibers (“top-down” modulation). Therefore, the theory also set an initial framework for psychological modulations on pain. Therefore, it suggested the existence of a descending modulatory system, which provided a physiological solution to those cases that could not be explained by previous pain theories (particularly because it offered possible explanations for aberrant pain after lesions of the nervous system). Although the Gate Control Theory was received with excitement and broadly accepted by the scientific community, it couldn’t provide a differentiation between distinct types of pain (cold, hot, visceral, dental), including those without an apparent sensory input (e.g. spinal cord injuries).

Figure 2 - Melzack and Wall’s Gate Control Theory of Pain (1965).

Reproduced from35.

Several seminal discoveries made in following years have shown in fact, that the mechanisms of pain transduction and perception are much more complex than described in the Gate Control Theory.

During this period (late 20th century), scientists have focused their investigation on the cellular arrangement of the central nervous system (CNS) and on the molecular mechanisms involved in nociception36–40. Few of those landmark discoveries were: the finding of various types of presynaptic inhibitors that can gate pain41–43, linking between evoked activity (impulses) in nociceptive afferent fibers and behavioral measures (at first in animals44,45, but later also in humans46–48), and the identification of pain-specific ascending pathways such as the Spinothalamic tract49–51. Critically, nociceptors were demonstrated to differ from low-threshold afferent fibers not only by having elevated thresholds for all stimuli ordinarily affecting a tissue, but also in their cellular properties52–56. On the cortical level, at first, pain was suggested to be a product of thalamic mechanisms, discounting a contribution by the cerebral cortex. This was based on studies showing absence of change in pain

(28)

26

perception following lesions or electrical stimulation57–60. Later, there was evidence in which cortical injuries resulted in a persisting loss of capacity to recognize painful stimulation in restricted body regions61–64. Taken together, at the beginning of the twenty-first century two things accepted by all pain researchers: (i) nociceptors are a separate class of primary sensory neurons that can discriminate reliably between noxious and innocuous stimulation, and (ii) nociceptive signals are processed in subcortical and cortical regions of the brain, leading to the perception of pain.

In response to all the new discoveries since his initial theory, Melzack proposed in 2001 a new theory – the Neuromatrix Model of pain65,66. In this theory, pain is defined as a multifaceted experience that is produced by a characteristic neurosignature of a widely distributed brain neural network, called the body–self neuromatrix65,66. The neuromatrix integrates cognitive–evaluative, sensory–discriminative, and motivational–affective aspects to engage perceptual, behavioral, and homeostatic systems in response pain. Since previous models (Specificity Theory, Pattern Theory, Gate Control Theory) mainly focused on peripheral mechanisms, they have difficulty in accounting observations of reported pain in patients with spinal cord injuries and in patients that experience phantom limb pain67–70. The body–

self neuromatrix, on the other hand, admits the possibility that somatic experiences (including pain) might also stem in the absence of any sensory input.

However, only with the advance of neuroimaging techniques (e.g. positron emission tomography (PET), and functional magnetic resonance imaging (fMRI)), neuroscientists could finally look inside the brain to find that administration of noxious stimuli activates a widespread network of brain regions better known as “the pain matrix” (Figure 3)71–80. Noxious stimulation evokes prominent signs of localized metabolic increases in several distinct cerebral cortical areas comprehending the comprehending primary (S1) and secondary (S2) somatosensory cortex, posterior (PI) and anteior (AI) insular cortex, the middle cingulate cortex (MCC), the thalamus, and the periaqueductal gray (PAG).

Figure 3 - NeuroSynth term-based meta-analyses of pain.

The likelihood of each coordinate belongs to studies investigating Pain [420 studies]. Neurosynth81,82.

(29)

27

At first, neuroimaging studies on pain have suggested that the pain matrix is a network unique to pain71–78. Indeed, the recruitment of this network has been replicated in studies employing different modalities of painful stimulations including: thermal (heat/cold), electrical (electric shock), mechanical (esophagus/rectal distention, ischemia, cutaneous pinprick), and chemical (checapsaicin, ascorbic acid, irritant odors such as CO2)83–86. Later neuroimaging studies, however, have started to speculate the precise role played by each region of the pain matrix, especially in light of studies which revealed how parts of pain matrix might be recruited in experimental manipulations involving pain, but in the absence of any noxious stimulation. These include, for instance, cases in which individuals were:

awaiting pain to occur (expectation paradigms)73,87–94, observing others in pain (empathic pain)95–100, reading texts describing painful situations101–105, or “suffering” following a social mistreatment by peers (social pain)106–109. Later neuroimaging studies suggested that due to the functional heterogeneity in the recruitment of the pain matrix, the pain matrix should be divided to parts involved in the processing of the sensory (e.g. intensity, noxiousness, location) or the affective (e.g.

unpleasantness, pain-related emotions, avoidance-goals) features of pain. For instance, the somatosensory cortex110 and the posterior portion of the insula were associated with the sensory processing of pain111, whereas the anterior part of the insula, the amygdala, and the cingulate cortex might be associated with affective processing of pain112–117.

However, the debate about the definition, the sources, and the signature of pain has not come into an end with the advances in neuroimaging. In respect to definitions, Craig (2003) considers pain as a homeostatic emotion that is both a specific interoceptive sensation and an integrated affective behavioral drive caused by a physiological imbalance118. Interestingly, the latter part can remind the physiological imbalance that was first mentioned by Hippocrates in Ancient Greece. On the other hand, Perl (2007) argues that the primary evidence for considering pain from noxious stimulation as a discriminative sense, rather than an emotion, is its dissociation from other body sensations in disorders of the nervous system8. Perl also criticizes Craig’s view by indicating that since homeostasis implies holding an organism and its systems to a stable state, it is a concept that poorly fit to pain, especially when a tissue is injured. In addition, there is also a current disagreement revolving around the sources of pain. For instance, events in which an individual is being excluded/rejected or mistreated by others, is advocated as a genuine form of pain (“social pain”)106,108,109,119. However, others have demonstrated a neural dissociation from physical pain, and suggest that these events should not be considered a form of pain120,121. As for the pain-matrix, following neuroimaging studies have shown that part of the pain matrix is also active in many affairs that are not pain, including other aversive experiences such as disgust (see Figure 4a-b), affective states (e.g. arousal), or even in prediction error. This finding opened a huge debate as to whether (and to which extent) the pain

(30)

28

matrix processes pain specifically122–125. Most importantly, it led scientists to offer a complete alternative views about the processing and the meaning of pain. For example, according to one view, pain is not a specific experience per se, but rather part of a larger system that processes salient signals in which pain is only one type of signal122,123. In another view, however, pain is a subjective experience that results from the interplay of prediction and prediction error signal about body damage126.

Figure 4 – Overlapping neural activity between pain & disgust.

(A) NeuroSynth81,82 term-based meta-analyses, reflecting the likelihood of each coordinate of being reported in studies investigating Pain [420 studies] and Disgust [78 studies]. (B) Shared neural activity between electrical pain and gustatory disgust127.

Even though there is still an ongoing debate among a number of researchers about the definition of pain, overall, the research community agrees at considering pain as a multi-component experience, which comprehends both sensory and affective aspects. This acknowledgment led to the current definition of pain and nociception, given by the International Association for the Study of Pain (IASP), according to which “(Pain is) an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described regarding such damage”128. This definition avoids tying pain to the stimulus, and allows researchers to consider phenomena which are not tissue-damaging - but still painful - as pain (e.g. social pain, empathic pain). To complement the IASP definition of pain that is widely accepted by pain researchers, it is also important to mention how the IASP defines

(31)

29

“nociception” and “noxious stimulus”. Accordingly, nociception is “The neural process of encoding noxious stimuli”. The consequences of encoding can be autonomic (e.g. elevated blood pressure) or behavioral (motor withdrawal reflex), but certainly cannot indicate on pain sensation. Whereas, a noxious stimulus is “a stimulus that is damaging or threatens damage to normal tissues". These two definitions are especially applicable for pain expectancy research, where anticipation periods can evoke neural processes to encode the impending noxious stimulus, without triggering a sensation of pain.

Overall, the development of pain theories from Ancient Greece to current times have provided us an insight into the numerous changes in the perspective of pain. Interestingly, this development seems to be non-linear, as older concepts of pain were reintroduced in modern theories of pain. Although the IASP definition (i.e. pain is an unpleasant multi-componential experience) is currently the most popular among pain researchers, clearly, it did not satisfy those who consider pain solely as an emotion118. Finally, whereas the technological advances throughout the years (e.g. functional neuroimaging) have solved previous queries on pain (e.g. whether the brain is involved in processing pain?), they also opened a door for many new questions (e.g. what is the exact involvement of each brain structure in the experience of pain? which factors can influence pain? what are the underlying mechanisms of pain modulators?). By investigating and (eventually) answering each of the questions emanating at the time, the more we understand pain, so we provide better ways to control it (e.g. use cognitive therapy, meditation, or develop more efficient drugs as treatments to alleviate suffering).

*Please note that in addition to the theories reviewed in this section, there are also other pain theories collectively termed “biopsychosocial models” of pain129–132. Similar to the body–self neuromatrix presented here, these theories use different integrations of biological and psychological aspects to define pain. Critically, however, the biopsychosocial models were formed to explain chronic pain - a type of pain which persists beyond the usual time associated with injury of a tissue, often regardless of presumed cause. This implies a difference from the usual relationship between tissue injury and rapid pain or nociceptive reactions. Therefore, these additional models of chronic pain were not included here as they go beyond the topical scope of the thesis.

2.1.2 History of disgust

In contrast to the deep roots of pain research, the interest in disgust started only at the early modern period. The very first definition of disgust was made in 1872, by Darwin, as "something revolting, primarily about the sense of taste, as perceived or vividly imagine, and secondarily to anything which causes a similar feeling, through the sense of smell, touch and even of eyesight"133. This definition already recognized the enormous variety of elicitors that can induce the feeling of disgust. The second

Références

Documents relatifs

The recent acquisition of a stable small colony variant (SCV strain JB1), generated from strain 6850 of Staphylococcus aureus, allowed us to study the susceptibilities to

There was no significant difference between Tbefore and T1, and between T6 and Tafter, suggesting that there was no audiotactile integration with the fixed

Dans ce travail, nous avons montré que l’inhibition pharmacologique des PI3Ks prévient la translocation nucléaire de l’EGFR en réponse à ses ligands et

Certains points critiques sont a discuté d’où l’application de la norme ISO 14001 ; on ce qui concerne la manière dont une entreprise élimine ou réduit ses déchets

Keywords: EMA/CHMP Guideline on clinical trials in small populations, Statistical methods, Statistical design, Statistical analysis, Small population clinical trials, Rare disease..

The advanced glycation end- product Nϵ -carboxymethyllysine promotes progression of pancreatic cancer: implications for diabetes- associated risk and its prevention: AGEs as

For 5 days per month of full resolution MIPAS operation, the standard deviation of the matching profile pairs is computed and compared with the precision given in the MIPAS Level

Shadow fera son chaos en ville .Quand Sonic arrivera, Shadow l’assommera puis il ira se cacher.. Toi Alice, quand les policiers viendront tu leur expliqueras que c’est Sonic qui a