Embodied effects of posture: Changing emotional and cognitive processes through the body

La cognición y emoción encarnada es un concepto que está revitalizando el interés por estudiar el papel del cuerpo en el procesamiento de información. Este concepto puede definirse como un efecto donde el cuerpo, su estado sensoriomotor, su morfología o su representación mental juega un papel fundamental en la configuración de los procesos cognitivos y emocionales. El cuerpo y sus procesos implicados han recibido escasa atención dentro de las teorías del procesamiento cognitivo que han predominado en las últimas décadas. No obstante, en los últimos años se ha producido un cambio en la forma de entender el procesamiento de la información, ya que la evidencia empírica señala que el cuerpo ejerce una gran influencia en la conformación de nuestros pensamientos y emociones. Estos hallazgos se enmarcan en las teorías de la cognición encarnada, en las cuales el supuesto básico es que el procesamiento de la información se encuentra influenciado, asociado, y a veces dependiente, de recursos perceptivos, somatosensoriales y motores. Por lo tanto, estas teorías asumen que la cognición o el procesamiento de la información puede depender de estados corporales y acciones físicas; y, en consecuencia, los estados cognitivos pueden influenciar los estados corporales asociados, y a la inversa. Diversos estudios experimentales avalan dicha relación bidireccional a través de la manipulación de la postura corporal. Así pues, una amplia evidencia empírica sugiere que adoptar una postura expansiva y/o erguida (versus encorvada y/o contraída) tiene efectos positivos en procesos cognitivos y emocionales. Sin embargo, los efectos derivados de la cognición encarnada apenas han sido estudiados en el campo de la psicopatología y la psicología clínica. En consecuencia, las terapias actuales basadas en la evidencia no se han beneficiados todo lo posible del uso de estrategias relacionadas con el cuerpo, que podrían ayudar a enriquecer y mejorar los resultados terapéuticos. Así pues, la presente tesis doctoral surgió de la necesidad de cubrir dicho vacío en la literatura científica, con el objetivo último de investigar cómo las estrategias relacionadas con el cuerpo −y específicamente, las manipulaciones de la postura corporal− podrían ser utilizadas con fines terapéuticos. Por ello, los objetivos principales de esta tesis consistieron en: (1) analizar el efecto de adoptar una postura corporal expansiva y erguida (versus contraída y encorvada) antes y durante la exposición a diversos estímulos ansiógenos (asociados a la ansiedad social y a los trastornos alimentarios) sobre procesos cognitivos y emocionales; (2) investigar el efecto de adoptar una postura erguida (versus encorvada) en la modificación de dos mecanismos asociados al mantenimiento de la depresión (los sesgos cognitivos de interpretación y las dificultades en generar imágenes mentales), así como en las emociones relacionadas; (3) explorar las posibles variables moderadoras y mediadoras que nos permitan conocer mejor para quién y cómo se producen los efectos de la postura corporal en los procesos cognitivos y emocionales; y (4) clarificar las posibles implicaciones clínicas de la manipulación de la postura corporal como estrategia terapéutica para la promoción de cambios cognitivos y emocionales. Para lograr dichos objetivos, se realizaron tres estudios experimentales en el contexto de laboratorio con claras implicaciones clínicas. Los estudios 1 y 2 tenían como objetivo analizar el papel de una postura expansiva y erguida (versus contraída y encorvada) en la exposición a estímulos ansiógenos: una audiencia (en el caso del estudio 1, en individuos con miedo a hablar en público) y el propio cuerpo (en el caso del estudio 2, en individuos con insatisfacción corporal). Por otra parte, el estudio 3 tenía como objetivo analizar el papel de la postura erguida (versus encorvada) en los sesgos cognitivos de interpretación, las dificultades en imaginación positiva y las emociones asociadas a la depresión. Los resultados señalan que adoptar una postura expansiva y erguida (versus una postura contraída y encorvada) tiene efectos beneficiosos sobre diversos procesos emocionales y cognitivos en muestras con sintomatología diversa (miedo a hablar en público, insatisfacción corporal y sintomatología depresiva). En el presente trabajo se discuten las implicaciones teóricas y clínicas respecto al papel del cuerpo en los procesos cognitivos y emocionales. No obstante, es necesario seguir investigando sobre los efectos encarnados de la postura corporal, ya que sólo la investigación nos ayudará a dilucidar cómo, cuándo, para quién y por qué adoptar una postura corporal específica podría ser beneficioso en el contexto terapéutico como una estrategia coadyuvante de las actuales terapias basadas en la evidencia

Social influence of siblings and friends in generation Y's development of risk preferences

Includes bibliographical refernces.Social influence can impact various characteristic of individual, including their beliefs, attitude and ultimately their behaviour. Social Marketing is an activity primarily concerned with identifying and modifying socially undesirable behaviours in a given population group. Adolescents typically receive the greatest amount of attention as they are highly prone to engaging in risky behaviour such as binge drinking, smoking and other dangerous activities

Dystopian Performatives: Negative Affect/Emotion in the Work of Sarah Kane

"Dystopian Performatives: Negative Affect/Emotion in the Work of Sarah Kane" seeks to combine three areas of theoretical inquiry to understand the way that affect/emotion operates on an audience in the theatre: affect/emotion science, performance theory, and utopianism. Utilizing Sarah Kane’s body of work as a case study, this dissertation connects each of her plays to a distinct basic emotion in order to bracket the vast interconnections between affect/emotion science and the theatre: disgust within Blasted, anger within Phaedra’s Love, fear within Cleansed, memory within Crave, and sadness within 4.48 Psychosis. Specifically, Dystopian Performatives investigates the negatively valenced experiences that occur in the theatre as a kind of dystopian practice that seeks to critique the present and promote action to adjust the future. The dystopian performative theory demonstrates the way in which experiential and viscerally impactful moments in the theatre potentially create change within an audience that directly attacks social and cultural issues relevant to the content of Kane’s plays. The experience of affect/emotion, I argue, performatively “does,” or acts, on the body of the audience in a way that has a meaningful impact on cognition, behavior, ideology, and morality

Ovarian hormones shape brain structure, function, and chemistry: A neuropsychiatric framework for female brain health

There are robust sex differences in brain anatomy, function, as well as neuropsychiatric and neurodegenerative disease risk (1-6), with women approximately twice as likely to suffer from a depressive illness as well as Alzheimer’s Disease. Disruptions in ovarian hormones likely play a role in such disproportionate disease prevalence, given that ovarian hormones serve as key regulators of brain functional and structural plasticity and undergo major fluctuations across the female lifespan (7-9). From a clinical perspective, there is a wellreported increase in depression susceptibility and initial evidence for cognitive impairment or decline during hormonal transition states, such as the postpartum period and perimenopause (9-14). What remains unknown, however, is the underlying mechanism of how fluctuations in ovarian hormones interact with other biological factors to influence brain structure, function, and chemistry. While this line of research has translational relevance for over half the population, neuroscience is notably guilty of female participant exclusion in research studies, with the male brain implicitly treated as the default model and only a minority of basic and clinical neuroscience studies including a female sample (15-18). Female underrepresentation in neuroscience directly limits opportunities for basic scientific discovery; and without basic knowledge of the biological underpinnings of sex differences, we cannot address critical sexdriven differences in pathology. Thus, my doctoral thesis aims to deliberately investigate the influence of sex and ovarian hormones on brain states in health as well as in vulnerability to depression and cognitive impairment:Table of Contents List of Abbreviations ..................................................................................................................... i List of Figures .............................................................................................................................. ii Acknowledgements .....................................................................................................................iii 1 INTRODUCTION .....................................................................................................................1 1.1 Lifespan approach: Sex, hormones, and metabolic risk factors for cognitive health .......3 1.2 Reproductive years: Healthy models of ovarian hormones, serotonin, and the brain ......4 1.2.1 Ovarian hormones and brain structure across the menstrual cycle ........................4 1.2.2 Serotonergic modulation and brain function in oral contraceptive users .................6 1.3 Neuropsychiatric risk models: Reproductive subtypes of depression ...............................8 1.3.1 Hormonal transition states and brain chemistry measured by PET imaging ...........8 1.3.2 Serotonin transporter binding across the menstrual cycle in PMDD patients .......10 2 PUBLICATIONS ....................................................................................................................12 2.1 Publication 1: Association of estradiol and visceral fat with structural brain networks and memory performance in adults .................................................................................13 2.2 Publication 2: Longitudinal 7T MRI reveals volumetric changes in subregions of human medial temporal lobe to sex hormone fluctuations ..............................................28 2.3 Publication 3: One-week escitalopram intake alters the excitation-inhibition balance in the healthy female brain ...............................................................................................51 2.4 Publication 4: Using positron emission tomography to investigate hormone-mediated neurochemical changes across the female lifespan: implications for depression ..........65 2.5 Publication 5: Increase in serotonin transporter binding across the menstrual cycle in patients with premenstrual dysphoric disorder: a case-control longitudinal neuro- receptor ligand PET imaging study ..................................................................................82 3 SUMMARY ...........................................................................................................................100 References ..............................................................................................................................107 Supplementary Publications ...................................................................................................114 Author Contributions to Publication 1 .....................................................................................184 Author Contributions to Publication 2 .....................................................................................186 Author Contributions to Publication 3 .....................................................................................188 Author Contributions to Publication 4 .....................................................................................190 Author Contributions to Publication 5 .....................................................................................191 Declaration of Authenticity ......................................................................................................193 Curriculum Vitae ......................................................................................................................194 List of Publications ................................................................................................................195 List of Talks and Posters ......................................................................................................19

Early effects of antidepressants on emotional processing

Introduction: The mechanisms of action of antidepressants at the system level remain mainly unresolved. Antidepressants rapidly modulate emotional processing, enhancing processing of positive versus negative information, but this has been mostly demonstrated in healthy subjects and using fairly simple, controlled emotional stimuli such as emotional faces. Aim of the study: The aim of the studies of this thesis was to shed light on early antidepressant effects on emotional processing both in healthy subjects, avoiding the confounding effect of depressed mood, and in treatment-seeking depressed patients at an early stage of treatment, to elude the confounding effect of improved mood. The studies specifically aimed to reveal antidepressant effects on self-referential processing, a core factor in psychopathology of depression, and to investigate whether/how antidepressants modulate processing of complex, dynamic emotional stimuli resembling daily-life emotional situations. Methods: In Study 1 (experiments I and II), an open-label study of 30 healthy volunteers, half of the subjects received mirtazapine 15 mg two hours prior to functional magnetic resonance imaging (fMRI), and the other half was scanned without medication as a control group. Study 2 (experiments III and IV) was a double-blind, placebo-controlled study where 32 treatment-seeking depressed patients were randomized to receive escitalopram 10 mg or placebo for one week, after which fMRI was performed. In experiments I and III, neural responses to positive and negative self-referential adjectives as well as a neutral control task were assessed. In experiments II and IV participants listened to spoken emotional narratives and neural responses to the emotional content of the narratives were assessed. Results: Both mirtazapine in healthy subjects and escitalopram in depressed patients modulated self-referential processing. Mirtazapine attenuated responses to both positive and negative self-referential words in the anterior cortical midline structures (CMS, including the medial prefrontal cortex and the anterior cingulate), whereas escitalopram increased processing of positive relative to negative self-referential words. When comparing the placebo group and the escitalopram group from Study 2 separately with the healthy controls from Study 1, depressed patients receiving placebo had decreased responses of the anterior CMS to positive versus negative self-referential words, whereas no differences were found between the escitalopram group and healthy controls, implicating normalization of the negative bias in depressed patients receiving escitalopram. Both mirtazapine and escitalopram also modulated brain responses to spoken emotional narratives. Mirtazapine was found to modulate dynamic functional connectivity (measured with seed-based phase synchronization) of large-scale brain circuits, particularly potentiating functional connectivity of the anterior CMS and the limbic regions during positive parts of the narratives. Escitalopram increased synchronization of brain responses (measured with inter-subject correlation, ISC), specifically during positive parts of the narratives. Conclusions: A single dose of mirtazapine in healthy subjects and a one-week treatment with escitalopram in treatment-seeking depressed patients modulated neural responses to emotional information without any concurrent changes in mood. Both antidepressants modulated self-referential processing, a core psychological process in developing and maintaining depression. Escitalopram normalized the negatively biased self-referential processing of depressed patients in the anterior CMS. Both mirtazapine and escitalopram modulated brain responses to spoken emotional narratives, extending the previous findings of antidepressant effects based on simple emotional stimuli to complex, dynamic, every-day like emotional situations. Specifically, potentiated processing measured with novel methods of dynamic functional connectivity and ISC was found in the anterior CMS among other regions during positive emotional content of the narratives. These results suggest that antidepressants rapidly modulate processing of particularly positive emotional and self-referential information in the anterior CMS. This may be important for their later therapeutic effect.Johdanto: Masennuslääkkeiden vaikutusmekanismeja systeemitasolla tunnetaan yhä heikosti. Niiden tiedetään vaikuttavan nopeasti tunteiden prosessointiin voimistamalla positiivisen informaation prosessointia negatiiviseen verrattuna. Tämä vaikutus on kuitenkin osoitettu lähinnä terveillä koehenkilöillä sekä käyttäen koeasetelmissa yksinkertaisia ärsykkeitä, kuten emotionaalisia kasvokuvia. Tavoitteet: Tämän väitöskirjatyön osatutkimusten tavoitteena oli selvittää masennuslääkkeiden varhaisia vaikutuksia tunteiden prosessointiin sekä terveillä koehenkilöillä, välttäen näin masentuneen mielialan sekoittava vaikutus, että masentuneilla potilailla hoidon varhaisessa vaiheessa, välttäen näin korjaantuvan mielialan sekoittava vaikutus. Erityisesti tavoitteena oli tutkia masennuslääkkeiden vaikutusta itseen liittyvään prosessointiin, koska liiallinen keskittyminen omiin, usein negatiivisiin tunteisiin ja ajatuksiin on eräs masennuksen keskeisistä psykologisista ilmiöistä. Lisäksi haluttiin selvittää, kuinka masennuslääkkeet vaikuttavat monimutkaisten, tosielämän emotionaalisia tilanteita muistuttavien ärsykkeiden prosessointiin. Menetelmät: Osatutkimuksessa 1 (koeasetelmat I ja II) puolet 30 terveestä vapaaehtoisesta sai avoimessa tutkimusasetelmassa 15mg mirtatsapiinia kaksi tuntia ennen toiminnallista magneettikuvausta (fMRI) ja puolet kuvattiin verrokkiryhmänä ilman lääkitystä. Osatutkimuksessa 2 (koeasetelmat III ja IV) 32 hoitoon hakeutunutta masennuspotilasta satunnaistettiin kaksois-sokkoutetussa tutkimusasetelmassa saamaan 10mg essitalopraamia tai lumetta viikon verran, jonka jälkeen suoritettiin fMRI-kuvaus. Koeasetelmissa I ja III mitattiin aivovasteita positiivisille ja negatiivisille itseen liittyville adjektiiveille sekä neutraaleille kontrollisanoille. Koeasetelmissa II ja IV koehenkilöt kuuntelivat kuvauksen aikana tunteita herättäviä tarinoita ja tarinoiden tunnesisällön herättämät aivovasteet mitattiin. Tulokset: Sekä mirtatsapiini terveillä koehenkilöillä että essitalopraami masennuspotilailla muokkasi aivovasteita itseen liittyviä sanoja prosessoitaessa. Mirtatsapiini vaimensi sekä positiivisten että negatiivisten sanojen herättämiä vasteita odotetuilla alueilla aivojen keskilinjan kortikaalisten alueiden etuosissa (keskimmäinen etuotsalohko ja etummainen pihtipoimu), kun taas essitalopraami voimisti positiivisten sanojen prosessointia negatiivisiin nähden masennuspotilailla. Kun osatutkimuksen 2 masennuspotilaiden aivovasteita verrattiin lume- ja lääkeryhmässä erikseen osatutkimuksen 1 terveisiin verrokkeihin, havaittiin lumeryhmän reagoivan heikommin positiivisiin sanoihin negatiivisiin nähden, kun taas lääkeryhmän ja terveiden verrokeiden välillä ei ollut eroa. Essitalopraami siis palautti masennuspotilaiden negatiivisesti vääristyneen itseen liittyvän prosessoinnin normaalille, terveelle tasolle. Molemmat masennuslääkkeet muovasivat aivovasteita emotionaalisten tarinoiden tunnesisällölle. Mirtatsapiini vaikutti laaja-alaisesti aivoalueiden välisiin toiminnallisiin yhteyksiin, erityisesti voimistamalla niitä aivojen keskilinja-alueiden etuosassa ja limbisellä alueella tarinoiden positiivisuuden lisääntyessä. Essitalopraami voimisti koehenkilöiden välistä synkroniaa aivovasteissa, erityisesti positiivisen sisällön aikana. Johtopäätökset: Molemmat tutkitut masennuslääkkeet vaikuttivat tunteiden prosessointiin nopeasti, ilman samanaikaista muutosta mielialassa. Essitalopraami normalisoi masennuspotilaiden negatiivisesti vääristynyttä itseen kohdistuvaa prosessointia, jonka ajatellaan olevan tärkeä tekijä masennustilan kehittymisessä ja jatkumisessa. Molemmat tutkitut masennuslääkkeet myös muokkasivat emotionaalisten tarinoiden herättämiä aivovasteita. Tämä tulos on merkittävä lisä aiempiin löydöksiin, koska se osoittaa masennuslääkkeiden muuttavan myös monimutkaisten ja dynaamisten, lähempänä todellisia arkipäivän tunteita herättäviä tilanteita olevien emotionaalisten ärsykkeiden prosessointia. Todetut muutokset voivat olla merkittävässä roolissa myöhemmän kliinisen lääkevasteen kannalta

Predicting and preventing relapse of depression in primary care: a mixed methods study

BackgroundMost people with depression are managed in primary care. Relapse (reemergence of depression symptoms after improvement) is common and contributes to the burden and morbidity associated with depression. There is a lack of evidence-based approaches for risk-stratifying people according to risk of relapse and for preventing relapse in primary care.MethodsIn this mixed methods study, I initially reviewed studies looking to predict relapse of depression across all settings. I then attempted to derive and validate a prognostic model to predict relapse within 6-8 months in a primary care setting, using multilevel logistic regression analysis on individual participant data from seven studies (n=1244). Concurrently, a qualitative workstream, using thematic analysis, explored the perspectives of general practitioners (GPs) and people with lived experience of depression around relapse risk and prevention in practice.ResultsThe systematic review identified eleven models; none could currently be implemented in a primary care setting. The prognostic model developed in this study had inadequate predictive performance on internal validation (Cstatistic 0.60; calibration slope 0.81). I carried out twenty-two semi-structured interviews with GPs and twenty-three with people with lived experience of depression. People with lived experience of depression and GPs reflected that a discussion around relapse would be useful but was not routinely offered. Both participant groups felt there would be benefits to relapse prevention for depression being embedded within primary care.ConclusionsWe are currently unable to accurately predict an individual’s risk ofdepression relapse. The longer-term care of people with depression ingeneral practice could be improved by enabling continuity of care, increased consistency and clarity around follow-up arrangements, and focussed discussions around relapse risk and prevention. Scalable, brief relapse prevention interventions are needed, which would require policy change and additional resource. We need to better understand existing interventions and barriers to implementation in practice

Understanding the relationship between chronic pain and emotional disorders

Although frequent coexistence of chronic pain and emotional disorders is well documented, exact mechanisms of comorbidity are not fully understood. The overarching aim of this thesis was to advance our knowledge of the mechanisms that link chronic pain and emotional disorders. Results of the literature review suggest that nosologically different conditions might coexist if they share common transdiagnostic risk factors that predispose individuals to several disorders. Using this transdiagnostic approach, a theoretical model explaining the relationships between different risk factors and how they might contribute to comorbidity between chronic pain and emotional disorders has been developed. According to the proposed model, one of the most fundamental transdiagnostic risk factors associated with both conditions is uncontrollable stress. It does not cause chronic pain or emotional disorders directly but promotes development of other risk factors, such as helplessness, negative affectivity, hypersensitivity to pain, dysregulation of stress response, and cognitive deficits. Importantly, these risk factors are not disorder specific. They equally predispose individuals to depression, anxiety, and chronic pain. Development of a specific disorder is determined by the influence of environmental and biological moderators that transform pre-existing risk factors into specific disorders. Considering that the sequence of pathological processes leading to psychopathology and/or chronic pain starts from the experience of uncontrollable stress, it is important to identify neural mechanisms that could mediate its effects. There is evidence suggesting that the frontal pole comprising of the rostromedial prefrontal cortex (rmPFC) and rostrolateral prefrontal cortex (rlPFC) plays an essential role in evaluation of controllability. Dysfunction of this area may increase the sense of uncontrollability, thereby promoting development of transdiagnostic risk factors. Both subregions of the frontal pole are parts of the neural networks that perform higher-order processing and modulation of nociceptive and emotional reactions. Thus, increased sensitivity to pain and heightened negative affect in patients with chronic pain disorders might be mediated by impaired interaction of the rmPFC and rlPFC with low-level nociceptive and emotional circuits. To test this hypothesis, resting-state functional and effective connectivity of the rmPFC and rlPFC was investigated in two chronic pain conditions: chronic low back pain (CLBP) and osteoarthritis (OA). Functional connectivity (FC) of the rmPFC and rlPFC in CLBP. CLBP patients displayed decreased FC of the rmPFC with retrosplenial cortex (RSC), posterior part of the ventral pallidum (VP), and mediodorsal (MD) thalamus. Diminished interaction with these regions may hinder retrieval of positive episodic memories of control and attribution of positive outcomes to personal actions. This may negatively influence patients’ belief about their ability to cope with stress, increase the sense of perceived uncontrollability. CLBP patients also showed reduced FC of the rmPFC with the medial pulvinar nucleus of the thalamus, midbrain reticular formation, and periaqueductal grey. These structures are parts of the ascending reticular activating system (ARAS) that regulates the level of arousal in the central nervous system. Reduced modulation of the arousal system by the rmPFC may result in development of a hyperarousal state and amplification of nociceptive and emotional responses leading to hyperalgesia and increased negative affectivity. There was no difference in FC of the rlPFC between CLBP patients and healthy controls. Effective connectivity analysis in CLBP. Causal interactions between the rmPFC, stress-related brainstem structures (dorsal raphe nucleus, ventral and dorsal periaqueductal grey), and memory systems (ventral striatum, hippocampus, amygdala) were investigated using the spectral dynamic causal modelling (spDCM). Consistent with the results of the FC analysis in CLBP, the spDCM also found altered interaction between the rmPFC and memory systems. Specifically, patients showed weaker connectivity of the rmPFC with hippocampus and stronger connectivity with the amygdala. Such pattern of connectivity may lead to inaccurate evaluation of the probability of control based on past experiences, overgeneralization and impaired extinction of fears. Patients also demonstrated hyperactivation of the dorsal raphe nucleus, ventral and dorsal periaqueductal grey (parts of the ARAS) that may contribute to hyperalgesia and increased negative affectivity. Functional connectivity of the rmPFC and rlPFC in OA. In this study FC of the rmPFC and rlPFC was compared between patients with shorter duration of OA (7 years), and healthy volunteers. Only patients with longer duration of OA showed increased negative FC of the rmPFC with multiple brainstem nuclei, such as the parabrachial complex, locus coeruleus, dorsal and median raphe nuclei, ventral tegmental area, midbrain reticular formation, and periaqueductal grey, that together comprise the ARAS. Negative FC between the rmPFC and ARAS may reflect increased compensatory inhibition of the activating system by the rmPFC in attempts to suppress pain-induced arousal and negative affect. Despite longer duration of pain, patients did not show signs of hyperalgesia or emotional distress. Perhaps, effective suppression of the brainstem arousal system demonstrated by OA patients was due to preserved connectivity between the rmPFC and memory systems. Both groups of OA patients also showed reduced FC of the rlPFC with the multiple demand network that may contribute to development of another transdiagnostic risk factor, i.e., cognitive deficit. Results of all three studies presented in this thesis suggest that chronic stress may cause development of transdiagnostic risk factors such as negative affectivity and hyperalgesia via hyperactivation of the brainstem arousal system that augments nociceptive and emotional responses. Impaired regulation of the arousal system by the rmPFC, which evaluates controllability of the stress based on previous experiences, may contribute to hyperactivation of the ARAS. Reduced interaction between the rmPFC and memory systems may obstruct retrieval and utilization of positive memories of control, thereby increasing the sense of uncontrollability, facilitating hyperarousal, and contributing to development of transdiagnostic risk factors. In contrast, preserved connectivity between the rmPFC and memory systems may oppose the negative effects of chronic stress and help patients to maintain a belief that they are capable of coping with the stress