Multimodal Neuroimaging of Emotion Regulation Strategies in Clinical and Healthy Control Samples

Abstract

Emotion regulation is a critical process for dealing appropriately with emotions in our daily lives. An important part of adaptively regulating emotions is being able to maintain a balance between short-term and long-term goals. There are different processes and strategies involved in emotion regulation, which can lead to different affective, cognitive and social outcomes. More importantly, these are altered in mental health disorders, with emotion regulation deficits appearing to be a transdiagnostic feature. Several functional magnetic resonance imaging (fMRI) studies and meta-analyses have shown a consistent pattern of neural activation during emotion regulation in healthy controls (HC), specifically for cognitive reappraisal tasks. This pattern of activations consists on a network of fronto-parietal control regions, which, in turn, down-regulates the limbic system (including the amygdala). On the other hand, preliminary findings from psychiatric populations indicate that the limbic system is overactive and prefrontal regulatory regions are compromised, showing both hyper and hypoactivations depending on the specific task. Further research is needed to better characterize whether the same pattern of affected neural activations is observed across different mental health disorders or whether a specific pattern of regional alterations emerges for different disorders, considering that most of these show deficits in emotion regulation in one way or another. To this end, the overall aim of this thesis was to provide new insights into the neural correlates of emotion regulation in clinical and HC samples, using different neuroimaging modalities. Specifically, Study 1 was the first using a dispositional approach looking into the intrinsic functional connectivity patterns associated with reappraisal and suppression use in a sample of HC. Then, in Study 2 this was further complemented with a sample of obsessive-compulsive disorder (OCD) patients and looking also at structural connectivity. Study 3 was the first to examine the fMRI cognitive reappraisal task in a sample of excess-weight participants, and the meta-analysis of fMRI cognitive reappraisal studies performed in Study 4 was the first one to include clinical samples and not just HC. From the results of these studies, we were able to draw the following conclusions: • The dispositional use of cognitive reappraisal and expressive suppression in HC subjects shows different neural correlates, with reappraisal use being related to basolateral amygdala (BLA)-insular and supplementary motor area (SMA) intrinsic functional connectivity, and suppression use being associated to BLA-dorsal anterior cingulate (dACC) and centromedial amygdala (CMA)-SMA functional connectivity. • There is an alteration in the insula across OCD, mood and anxiety disorders, and excess-weight individuals, a region that is critically involved in emotional awareness and valuation. • OCD patients show decreased functional and structural connectivity between the right amygdala and the right post-central gyrus. Moreover, the association between amygdala’s functional connectivity and habitual reappraisal and suppression use is altered in comparison with HC, with microstructural alterations in underlying white-matter tracts connecting these regions. • Excess-weight individuals show decreased attentional involvement during the experimentation of emotions, and increased emotional reactivity during emotion regulation, as indicated by decreased insula, orbitofrontal cortex, and cerebellum activity during the Maintain>Observe contrast, and increased insula activity during the Regulate>Maintain contrast. • Other alterations in mood and anxiety disorders encompass decreased activations in the prefronto-parietal regulatory network during cognitive reappraisal, as well as increased activations in attentional and parietal compensatory regions. • According to our findings, there are deficits in emotion regulation shared across different disorders, although there are also specific deficits for different disorder groups, emphasizing the need of subject-wise brain-based treatments targeting individual needs. This thesis contributes to expand the knowledge about the underlying neurobiology of emotion regulation across conditions and mental health disorders, leading to a better understanding of the commonalities and differences in patient groups with impairments in these processes, and eventually providing new targets for brain-based treatments of emotion regulation deficits.

La regulació emocional és un procés necessari per gestionar de manera apropiada les emocions en el nostre dia a dia. Hi ha diferents estratègies de regulació emocional que comporten diferents conseqüències afectives, cognitives i socials. Encara més important, aquestes pareixen estar afectades als trastorns psiquiàtrics, podent considerar els dèficits de regulació emocional com una característica transdiagnòstica. Diferents estudis i meta-anàlisis de ressonància magnètica funcional (RMf) han mostrat un patró d’activació neural durant la regulació emocional en controls sans, que consisteix en una xarxa prefronto-parietal de regions regulatòries, encarregada de regular a la baixa l’activació del sistema límbic (incloent l’amígdala). En canvi, als trastorns psiquiàtrics, resultats preliminars indiquen que el sistema límbic podria estar hiperactiu i les regions regulatòries prefrontals es trobarien alterades. Es necessiten més estudis per poder determinar si s’observa el mateix patró d’activacions neurals afectades en diferents trastorns psiquiàtrics, o si hi ha un patró específic per cada trastorn, tenint en compte que en la majoria de trastorns predominen els dèficits de regulació emocional d’una manera o altra. Per això, l’objectiu d’aquesta tesi és oferir noves dades respecte als correlats neurals de la regulació emocional en mostres clíniques i controls sans. S’han utilitzat diferents modalitats de neuroimatge per poder oferir una millor descripció d’aquests correlats i la seua relació amb diferents estratègies de regulació emocional. Concretament, l’Estudi 1 de la tesi és el primer en examinar com s’associa la connectivitat funcional intrínseca en una mostra de controls sans amb l’ús habitual d’estratègies de reavaluació cognitiva i de supressió. En l’Estudi 2, a més, això es veu complementat amb la comparació amb pacients amb trastorn obsessiu-compulsiu, i també es compara la connectivitat estructural. A l’Estudi 3 s’estudia per primera vegada la tasca de reavaluació cognitiva en RMf en una mostra de subjectes amb excés de pes, i a l’Estudi 4 es fa un meta-anàlisi d’estudis que utilitzen aquesta tasca en diferents mostres clíniques. D’acord amb els nostres resultats, existeixen dèficits de regulació emocional compartits a través dels diferents trastorns, però també hi ha dèficits específics per als diferents grups de trastorns, el qual posa encara més èmfasi en la necessitat de desenvolupar tractaments personalitzats basats en el coneixement neurobiològic i enfocats a millorar les necessitats individuals.