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Mental imagery refers to sensory-perceptual experiences in the absence of external sensory input. Emotional mental imagery (i.e., imagery with emotional content) is a key feature in many mental disorders, such as the image-based intrusive memories of trauma in posttraumatic stress disorder (PTSD). However, mental imagery can also be a vehicle for emotional change. In imaginal exposure, fear-provoking events are revisited using mental imagery. Imaginal exposure is a core component in evidence-based therapies for anxiety and PTSD. Treatment development is needed, as effects are many times insufficient, accessibility is low, and the treatment is not well-tolerated by some patients. The aim of this thesis was to increase knowledge of underlying mechanisms of imaginal exposure and improve our understanding of emotional mental imagery. The thesis explored the neural underpinnings of imaginal exposure and investigated mechanisms that could enhance its effectiveness, accessibility and tolerability. To further our knowledge of intrusive memories in PTSD (i.e., involuntary mental imagery), the characteristics of trauma memory hotspots (worst moments) collected within the first hours after trauma were explored. Study I demonstrated that imaginal exposure to mental imagery of phobic (vs. neutral) stimuli robustly activated emotion-processing brain areas. Study I also revealed that a brief 10-minute session of imaginal exposure was associated with reduced fear one week later. Study II investigated the link between vividness (clarity and liveliness) of mental imagery during imaginal exposure and reduction of fear using an experimental analogue of imaginal exposure (imaginal extinction). No evidence was found that high imagery vividness during imaginal extinction was associated with better long-term reduction in physiological fear responses than lower vividness. Study III revealed that hotspots collected soon after trauma are expressed as motion-rich sensory-perceptual experiences (mental imagery) with little detail on emotion/cognition. The contributions of this thesis involve demonstrating that mental imagery has the power to elicit emotional responses at subjective, physiological and neural levels and suggesting new avenues for treatment development. Future studies should explore the benefits of briefer imaginal exposure sessions to improve the effectiveness and accessibility of imaginal exposure. Future studies should also examine if fear reduction can be obtained with less vivid imaginal exposure, which could help attenuate distress and thereby make imaginal exposure tolerable for more patients. Lastly, the dynamic and visuospatial nature of newly formed trauma memory hotspots may help elucidate mechanisms through which tasks conducted posttrauma can prevent intrusive memories.

Social anxiety disorder (SAD) can come in different forms, presenting problems for diagnostic classification. Here, we examined personality traits in a large sample of patients (N = 265) diagnosed with SAD in comparison to healthy controls (N = 164) by use of the Revised NEO Personality Inventory (NEO-PI-R) and Karolinska Scales of Personality (KSP). In addition, we identified subtypes of SAD based on cluster analysis of the NEO-PI-R Big Five personality dimensions. Significant group differences in personality traits between patients and controls were noted on all Big Five dimensions except agreeableness. Group differences were further noted on most lower-order facets of NEO-PI-R, and nearly all KSP variables. A logistic regression analysis showed, however, that only neuroticism and extraversion remained significant independent predictors of patient/control group when controlling for the effects of the other Big Five dimensions. Also, only neuroticism and extraversion yielded large effect sizes when SAD patients were compared to Swedish normative data for the NEO-PI-R. A two-step cluster analysis resulted in three separate clusters labelled Prototypical (33%), Introvert-Conscientious (29%), and Instable-Open (38%) SAD. Individuals in the Prototypical cluster deviated most on the Big Five dimensions and they were at the most severe end in profile analyses of social anxiety, self-rated fear during public speaking, trait anxiety, and anxiety-related KSP variables. While additional studies are needed to determine if personality subtypes in SAD differ in etiological and treatment-related factors, the present results demonstrate considerable personality heterogeneity in socially anxious individuals, further underscoring that SAD is a multidimensional disorder. Funding Agencies|Swedish Research CouncilSwedish Research Council [2016-0228]; Riksbankens Jubileumsfond - the Swedish Foundation for Research in Social Sciences and the Humanities [P17-0639:1]

Animal studies indicate that substance P (SP) and its preferred neurokinin-1 (NK1) receptor modulate stress and anxiety-related behavior. Alterations in the SP-NK1 system have also been observed in human anxiety disorders, yet little is known about the relation between this system and individual differences in personality traits associated with anxiety propensity and approach-avoidance behavior, including trait anxiety, neuroticism, and extraversion. Exploring this relation could provide important insights into the neurobiological underpinnings of human anxiety and the etiology of anxiety disorders, as anxious traits are associated with increased susceptibility to develop psychopathological conditions. Here we examined the relationship between central NK1 receptor availability and self-rated measures of trait anxiety, neuroticism, and extraversion. The amygdala was chosen as the primary region of interest since this structure has been suggested to mediate the effect of the SP-NK1 system on anxiety. Anxious traits and NK1 receptor availability, determined with positron emission tomography and the radiotracer [11C]GR205171, were measured in 17 healthy individuals. Voxel-wise analyses showed a significant positive correlation between bilateral amygdala NK1 receptor availability and trait anxiety, and a trend in similar direction was observed for neuroticism. Conversely, extraversion was found to be negatively associated with amygdala NK1 receptor availability. Extraversion also correlated negatively with the NK1 measure in the cuneus/precuneus and fusiform gyrus according to exploratory whole-brain analyses. In conclusion, our findings indicate that amygdala NK1 receptor availability is associated with anxiety-related personality traits in healthy subjects, consistent with a modulatory role for the SP-NK1 system in human anxiety.