This thesis contains an introduction to anatomy and physiology of the skin highlighting its barrier function. The barrier function of the skin enables it to separate internal organism from external environment. thermore, the electrical properties of the skin are described and possibilities of skin conductance measurement are discussed. The thesis presents a design of a device for the skin conductance measurement as the method of evaluation for barrier function. Alternating current is used for measurement during iontophoresis for evaluation of skin conductance. Circuit design and circuit board are included with a list of parts. The designed device was realized and in the end it was tested and the results were discussed.

Emotions are an integral part of the human experience and their interpretation can provide valuable but also misleading clues about oneself and other people’s state of mind. Negative emotional states can be perceived as uncomfortable and – when experienced chronically – can develop into anxiety and mood disorders. The more pervasive these disorders the more severely they affect and disable a person’s everyday functioning and often their sleep as well. According to Lang and colleagues (1998), emotions may be expressed verbally, behaviorally, and physiologically, i.e., emotions can be reported, observed, and objectively measured. Each measurement approach provides important, unique, and often conflicting information that can be used in the assessment and treatment evaluation of psychological disorders affecting the emotions. Autonomic measures have been used to indicate the physiological components of emotions, such as those along the worry-anxiety-fear-panic spectrum. Worry has been shown to suppress cardiac responses to imaginal feared material (see Borkovec, Alcaine, & Behar, 2004) and reduce autonomic variability (Hoehn-Saric, McLeod, Funderburk, & Kowalski, 2004; Hoehn-Saric, McLeod, & Zimmerli, 1989). Results for panic and anticipatory anxiety are less conclusive but theoretically these states should go along with increased autonomic arousal. Abnormal autonomic arousal might also be present during sleep as both panic disorder and worrying have been associated with sleeping difficulties. However, most empirical research has been confined to the laboratory where high internal validity is achieved at the cost of poor ecological validity. Thus, the purpose of this doctoral dissertation is to extend and validate laboratory findings on worry, anticipatory anxiety, and panic using ambulatory monitoring. Twenty-four hour monitoring not only can give valuable insights into a person’s daytime emotional experience but also allows observing how these emotions might affect their sleep in their natural environment. In the following chapter, the reader will be introduced to a conceptual framework that ties together worry, anxiety, fear, and panic, and related anxiety disorders (section 2.1), to autonomic arousal and electrodermal and cardiac arousal in particular (section 2.2), to sleep and its relation to autonomic arousal and anxiety disorders (section 2.3), and to ambulatory monitoring (section 2.4). After illustrating the aims of this thesis (chapter 3), chapters 4 to 6 present the results of three empirical studies conducted as part of this doctoral research. The first study deals solely with electrodermal monitoring and how it is affected by confounding variables in an ambulatory context (chapter 4). The next study then seeks to investigate the relationship between electrodermal arousal and anticipatory anxiety and panic in a sample of panic disorder patients and healthy controls. The last study focuses primarily on the effect of trait and state worry on subjective and objective sleep and electrodermal and cardiac arousal in a group of high and low worriers. Chapters 7 to 9 summarize and integrate the findings from these three empirical studies, discuss methodological limitations, and provide an outlook into future research.

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Background: Neurophysiological models link dissociation (e.g. feeling detached during or after a traumatic event) to hypoarousal. It is currently assumed that the initial passive reaction to a threat may coincide with a blunted autonomic response, which constitutes the dissociative subtype of post-traumatic stress disorder (PTSD). - Objective: Within this systematic review we summarize research which evaluates autonomic nervous system activation (e.g. heart rate, blood pressure) and dissociation in PTSD patients to discern the validity of current neurophysiological models of trauma-related hypoarousal. - Method: Of 553 screened articles, 28 studies (N = 1300 subjects) investigating the physiological response to stress provocation or trauma-related interventions were included in the final analysis. - Results: No clear trend exists across all measured physiological markers in trauma-related dissociation. Extracted results are inconsistent, in part due to high heterogeneity in experimental methodology. - Conclusion: The current review is unable to provide robust evidence that peri- and posttraumatic dissociation are associated with hypoarousal, questioning the validity of distinct psychophysiological profiles in PTSD.

The present study examined the ability of a Virtual Reality (VR) public speaking task to elicit physiological arousal in adults with SAD (n=25) and Controls (n=25). A behavioral assessment paradigm was employed to address three study objectives: (a) to determine whether the VR task can elicit significant increases in physiological response over baseline resting conditions (b) to determine if individuals with SAD have a greater increase from baseline levels of physiological and self-reported arousal during the in vivo speech task as opposed to the VR speech task and (c) to determine whether individuals with SAD experience greater changes in physiological and selfreported arousal during each speech task compared to controls. Results demonstrated that the VR task was able to elicit significant increases in heart rate, skin conductance, and respiratory sinus arrhythmia, but did not elicit as much physiological or self-reported arousal as the in vivo speech task. In addition, no differences were found between groups. Clinical implications of these findings are discussed

La douleur est une expérience subjective multidimensionnelle accompagnée de réponses physiologiques. Ces dernières sont régulées par des processus cérébraux qui jouent un rôle important dans la modulation spinale et cérébrale de la douleur. Cependant, les mécanismes de cette régulation sont encore mal définis et il est essentiel de bien les comprendre pour mieux traiter la douleur. Les quatre études de cette thèse avaient donc comme objectif de préciser les mécanismes endogènes de modulation de la douleur par la contreirritation (inhibition de la douleur par une autre douleur) et d’investiguer la dysfonction de ces mécanismes chez des femmes souffrant du syndrome de l’intestin irritable (Sii). Dans un premier temps, un modèle expérimental a été développé pour mesurer l’activité cérébrale en imagerie par résonance magnétique fonctionnelle concurremment à l’enregistrement du réflexe nociceptif de flexion (RIII : index de nociception spinale) et des réponses de conductance électrodermale (SCR : index d’activation sympathique) évoqués par des stimulations électriques douloureuses. La première étude indique que les différences individuelles d’activité cérébrale évoquée par les stimulations électriques dans les cortex orbitofrontal (OFC) et cingulaire sont associées aux différences individuelles de sensibilité à la douleur, de réactivité motrice (RIII) et de réactivité autonomique (SCR) chez des sujets sains. La deuxième étude montre que l’analgésie par contreirritation produite chez des sujets sains est accompagnée de l’inhibition de l’amygdale par OFC et d’une modulation du réflexe RIII par la substance grise périaqueducale (PAG) et le cortex somesthésique primaire (SI). Dans les troisième et quatrième études, il est montré que la contreirritation ne produit pas d’inhibition significative de la douleur et du réflexe RIII chez les patientes Sii en comparaison aux contrôles. De plus, les résultats indiquent que la sévérité des symptômes psychologiques est associée au déficit de modulation de la douleur et à une hypersensibilité diffuse chez les patientes Sii. Dans l’ensemble, cette thèse précise le rôle de certaines structures cérébrales dans les multiples composantes de la douleur et dans l’analgésie par contreirritation et montre que les patientes Sii présentent une dysfonction des mécanismes spinaux et cérébraux impliqués dans la perception et la modulation de la douleur. / Pain is a subjective experience comprising multiple dimensions and is accompanied by physiological responses. These responses are regulated by neural processes that play a crucial role in cerebral and spinal modulation of pain. However, the mechanisms of this regulation are still not clear and a better understanding of these processes is essential in order to treat pain effectively. The four studies of this thesis were intended to define the central mechanisms of endogenous pain modulation by counterirritation (application of two competing noxious stimuli) and to investigate the dysfunction of these mechanisms in female patients with irritable bowel syndrome (IBS). First, an experimental model was developed in which functional magnetic resonance imaging was used to measure brain activity concurrently to the recording of the nociceptive flexion reflex (RIII: an index of spinal nociceptive processes) and skin conductance responses (SCR: an index of sympathetic activation). The first study indicates that individual differences in shock-evoked brain activity in the orbitofrontal (OFC) and cingulate cortices are associated with individual differences in pain sensitivity, motor reactivity (RIII), and autonomic reactivity (SCR) in healthy volunteers. In the second study, it is shown that counterirritation analgesia produced in healthy volunteers is accompanied by the inhibition of the amygdala by the OFC, and the inhibition of the RIII reflex by the periacqueductal gray matter (PAG) and the primary somatosensory cortex (SI). In the third and fourth studies, pain and RIII reflex were not significantly modulated by counterirritation in patients with IBS in comparison to healthy controls. Furthermore, the severity of psychological symptoms was associated with pain modulation deficits and diffuse hypersensitivity in IBS patients. Together, the results of these studies clarify the functions of pain-related activity in specific brain structures and the mechanisms underlying counterirritation analgesia. Moreover, it is concluded that patients with IBS show a dysfunction of cerebral and spinal processes involved in both the perception and modulation of pain.

Le nouveau-né hospitalisé est exposé de manière répétée à des procédures douloureuses ou stressantes pouvant entraîner des conséquences neurodéveloppementales à court et long terme. La prévention de la douleur procédurale est essentiellement basée sur l’utilisation de traitements non pharmacologiques parmi lesquels les solutions sucrées possèdent un niveau de preuve élevé. Cependant, leur efficacité a récemment été remise en cause et leurs mécanismes d’action restent mal compris. Enfin, la dissociation parfois retrouvée entre les réponses comportementales et corticales suggère de monitorer la douleur de manière multimodale. Les objectifs de ce travail étaient : 1) de comparer l’efficacité de l’allaitement maternel et du sucrose sur la douleur procédurale en analysant spécifiquement les réponses corticales, 2) d’étudier les effets périphériques des solutions sucrées au niveau de neurones sensoriels de ratons, 3) d’évaluer l’intérêt d’un modèle d’évaluation multimodale de la douleur chez le nouveau-né à terme et prématuré. Aucune différence entre le sucrose et l’allaitement maternel n’a pu être objectivée sur les réponses corticales(NIRS) à la douleur chez des nouveau-nés à terme à 3 jours de vie. Nous avons objectivé un effet périphérique du glucose et du sucrose sur des neurones sensoriels de ratons nouveau-nés, médié par TRPV1. L'effet du glucose était associé à une diminution de la libération de la substance P. L’évaluation multimodale de la douleur retrouvait des corrélations faibles à modérées entre le score NFCS et la conductance cutanée, le cortisol salivaire et les changements d’ [HbT] mesurés en NIRS. L’étude menée chez les nouveau-nés prématurés nous permettra de préciser l’intérêt de l’utilisation de la variabilité de la fréquence cardiaque (indice NIPE instantané) dans cette indication afin de proposer un modèle multimodal fiable pour de futurs essais randomisés contrôlés. / Hospitalized newborns are exposed to repeated painful or stressful procedures that can lead to short- and long-term neurodevelopmental sequellae.The prevention of procedural pain is essentially based on the use of nonpharmacological treatments among which the sweet solutions appear to be among the most effective. However, their effectiveness has recently been challenged and their mechanisms of action remain poorly understood. Finally, the dissociation frequently found between behavioural and cortical responses shows the importance of monitoring pain in a multimodal way. The objectives of this work were 1) to compare the efficacy of breastfeeding and sucrose on procedural pain by specifically analyzing cortical responses, 2) to study the peripheral effects of sweet solutions on sensory neurons of newborn rats and 3) to evaluate the contribution of a multimodal pain assessment model in term and preterm neonates. No difference between sucrose and breastfeeding was measured on pain-evoked cortical responses (NIRS) in term neonates at 3 days of life.We reported a peripheral effect of glucose and sucrose on afferent sensory neurons from newborns rats mediated byTRPV1. The effect for glucose was associated with a decrease of substance P release.The multidimensional assessment of pain found mild to moderate correlations between the NFCS score, skin conductance, salivary cortisol and changes in [HbT] measured in NIRS.The study conducted in preterm newborns will specify the reliability of heart rate variability (instant NIPE index) in thisindication to provide a suited multimodal pain assessment model for future randomized controlled trials.

Ergänzend zu bestehenden Verfahren Bewältigungsverhalten zu erfassen, versucht die vorliegende Studie mittels eines mehrdimensionalen Ansatzes neue Wege der psychosomatischen Grundlagenforschung zu eröffnen. Anhand des Biopsychologischen Belastungstests werden erlebens- (Annäherungsmotivation, Meidungsmotivation, Traitangst), verhaltens- und peripherpsychologische (Herzfrequenz, Hautleitwertreaktion) Parameter einer heterogenen Stichprobe aus gesunden Kontrollprobandinnen und psychosomatischen Patientinnen erhoben. Diese Parameter sollen eine Einteilung der Testpersonen in Untergruppen ermöglichen, um die Identifizierung von repressiv, optimistisch und konflikthaft bewältigenden Personen vornehmen zu können. In den Analysen lässt sich die Aufteilung der Untergruppen im hypothetisierten Rahmen allerdings nicht wiederfinden. Es zeigen sich signifikante Unterschiede zwischen den Motivationsebenen der Testpersonen (Annäherungsmotivation/Meidungsmotivation jeweils hoch/niedrig), sowie kontinuierlich signifikante Unterschiede zwischen den gesunden Kontrollprobandinnen und den psychosomatischen Patientinnen. Zusätzlich finden sich enge Parallelen zwischen Traitangst und Meidungsmotivation. / The following study proposes additionally to present methods a new multidimensional approach in psychosomatic research. Experience (approach motivation, avoidance motivation, trait-anxiety), behavioural, and peripher-psychological (heart frequency, skin conductance response) parameters are collected utilizing the Biopsychologischer Belastungstest (BBT). Using these parameters it is intended to separate test persons into clusters allowing the discrimination of coping patterns repression, optimism, and intra-personal approach avoidance conflict. The hypothesized subgroups can not be approved by the results of cluster analysis. However, significant differences between high and low approach respectively avoidance motivated test persons are found. Furthermore, throughout the analysis significant differences between "healthy" control persons and the psychosomatic patients are visible. In addition it can be emphasized that trait-anxiety is closely related to avoidance motivation.

During pregnancy, the basal activity is increased in both of our major stress response systems: the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. At the same time, the reactivity towards stressors is reduced. These alterations sustain maternal and fetal homeostasis, and are involved in the regulation of gestational length. Although the feto-placental hormone synthesis produces the main endocrinological changes, also the central nervous system undergoes adaptation. Together, these profound adjustments have been suggested to make women’s mental health more vulnerable during pregnancy and postpartum period. The aim of this thesis was to examine factors connected to physiological stress responses during the late pregnancy in relation to pain, labour onset, emotional reactivity, and mental health. The first study examined the pain and sympathetic response during cold stress, in relation to time to delivery. Women with fewer days to spontaneous delivery had lower sympathetic reactivity, while no pain measure was associated with time to delivery. In the second study, acoustic startle response modulation was employed to study emotional reactivity during late gestation, and at four to six weeks postpartum. The startle response was measured by eye-blink electromyography, while the participants watched pleasant and unpleasant pictures, and positive and negative anticipation stimuli. A significant reduction in startle modulation by anticipation was found during the postpartum assessment. However, no startle modulation by pleasant, or unpleasant, pictures was detected at either time-point. The serum level of allopregnanolone, a neurosteroid implied in pregnancy-induced hyporeactivity, was analysed in relation to self-reported symptoms of anxiety and depression. Although the participants reported low levels of depression, the women with the highest depression scores had significantly lower levels of serum allopregnanolone. There was no correlation between allopregnanolone and anxiety scores. In the fourth study, the cortisol awakening response was compared between women with depression during pregnancy, women with depression prior to pregnancy, and women who had never suffered from depression. No group differences in cortisol awakening response during late pregnancy were found. The results are in line with the previously described pregnancy-induced hyporesponsiveness, and add to the knowledge on maternal stress hyporeactivity, gestational length, and maternal mental health.

La douleur est une expérience subjective multidimensionnelle accompagnée de réponses physiologiques. Ces dernières sont régulées par des processus cérébraux qui jouent un rôle important dans la modulation spinale et cérébrale de la douleur. Cependant, les mécanismes de cette régulation sont encore mal définis et il est essentiel de bien les comprendre pour mieux traiter la douleur. Les quatre études de cette thèse avaient donc comme objectif de préciser les mécanismes endogènes de modulation de la douleur par la contreirritation (inhibition de la douleur par une autre douleur) et d’investiguer la dysfonction de ces mécanismes chez des femmes souffrant du syndrome de l’intestin irritable (Sii). Dans un premier temps, un modèle expérimental a été développé pour mesurer l’activité cérébrale en imagerie par résonance magnétique fonctionnelle concurremment à l’enregistrement du réflexe nociceptif de flexion (RIII : index de nociception spinale) et des réponses de conductance électrodermale (SCR : index d’activation sympathique) évoqués par des stimulations électriques douloureuses. La première étude indique que les différences individuelles d’activité cérébrale évoquée par les stimulations électriques dans les cortex orbitofrontal (OFC) et cingulaire sont associées aux différences individuelles de sensibilité à la douleur, de réactivité motrice (RIII) et de réactivité autonomique (SCR) chez des sujets sains. La deuxième étude montre que l’analgésie par contreirritation produite chez des sujets sains est accompagnée de l’inhibition de l’amygdale par OFC et d’une modulation du réflexe RIII par la substance grise périaqueducale (PAG) et le cortex somesthésique primaire (SI). Dans les troisième et quatrième études, il est montré que la contreirritation ne produit pas d’inhibition significative de la douleur et du réflexe RIII chez les patientes Sii en comparaison aux contrôles. De plus, les résultats indiquent que la sévérité des symptômes psychologiques est associée au déficit de modulation de la douleur et à une hypersensibilité diffuse chez les patientes Sii. Dans l’ensemble, cette thèse précise le rôle de certaines structures cérébrales dans les multiples composantes de la douleur et dans l’analgésie par contreirritation et montre que les patientes Sii présentent une dysfonction des mécanismes spinaux et cérébraux impliqués dans la perception et la modulation de la douleur. / Pain is a subjective experience comprising multiple dimensions and is accompanied by physiological responses. These responses are regulated by neural processes that play a crucial role in cerebral and spinal modulation of pain. However, the mechanisms of this regulation are still not clear and a better understanding of these processes is essential in order to treat pain effectively. The four studies of this thesis were intended to define the central mechanisms of endogenous pain modulation by counterirritation (application of two competing noxious stimuli) and to investigate the dysfunction of these mechanisms in female patients with irritable bowel syndrome (IBS). First, an experimental model was developed in which functional magnetic resonance imaging was used to measure brain activity concurrently to the recording of the nociceptive flexion reflex (RIII: an index of spinal nociceptive processes) and skin conductance responses (SCR: an index of sympathetic activation). The first study indicates that individual differences in shock-evoked brain activity in the orbitofrontal (OFC) and cingulate cortices are associated with individual differences in pain sensitivity, motor reactivity (RIII), and autonomic reactivity (SCR) in healthy volunteers. In the second study, it is shown that counterirritation analgesia produced in healthy volunteers is accompanied by the inhibition of the amygdala by the OFC, and the inhibition of the RIII reflex by the periacqueductal gray matter (PAG) and the primary somatosensory cortex (SI). In the third and fourth studies, pain and RIII reflex were not significantly modulated by counterirritation in patients with IBS in comparison to healthy controls. Furthermore, the severity of psychological symptoms was associated with pain modulation deficits and diffuse hypersensitivity in IBS patients. Together, the results of these studies clarify the functions of pain-related activity in specific brain structures and the mechanisms underlying counterirritation analgesia. Moreover, it is concluded that patients with IBS show a dysfunction of cerebral and spinal processes involved in both the perception and modulation of pain.