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Internet-delivered cognitive behavior therapy (CBT) for social anxiety disorder is an evidence-based treatment in regular health care. Still, a considerable proportion of treated patients do not respond. There is also a debate on the importance of patients expectations’ for therapeutic outcomes. However, experimental evidence is lacking to answer this question. Our aim is thus to investigate the placebo response in social anxiety disorder, and the link between initial placebo responsiveness and subsequent outcome of CBT. First, we will manipulate expectations of anxiety relief. A benzodiazepine (a common anti-anxiety drug) will be administered with correct or incorrect information about clinical efficacy during a public speaking task. Self-reports and moment-to-moment variability in neural response will be measured with functional magnetic resonance imaging (fMRI) during the manipulation of expectations. The balanced placebo design allows us to dissect the total treatment effect into its components: drug, placebo, and interactions between the two. Second, patients undergo internet-delivered CBT after completing the placebo experiments. This project aims to unravel expectations´ influence on treatment response, and has a two-fold significance, 1) the scientific understanding of the neural mechanisms of treatment expectations, central for placebo, and 2) the development of pre-treatment predictors of CBT outcome which could improve precision in clinical decision making.

The question of how emotions are triggered remains obscure. A recent influential theory is built on predicting coding, which states that the brain makes predictions and constantly compares these predictions with the actual incoming sensory information. The active inference theory of emotions posits that emotions arise when there is a mismatch between the bodily (interoceptive) sensations and what was predicted by the brain, i.e. when interoceptive prediction errors occur. This theory is extremely relevant for emotional disorders linked with infections (e.g. post-COVID), since infections can trigger various and intense interoceptive signals that can be difficult to predict by the brain. In this project, we will apply the active inference theory of emotions in an ecologically relevant model of infection, using an innovative experimental approach. We will go beyond the existing correlational designs by applying a causal intervention eliciting real sickness symptoms, and manipulating interoceptive prediction errors directly, in 240 participants. We hypothesize that emotional responses will arise during sickness when interoceptive prediction errors occur, i.e. when interoceptive sensations violate predictions. This project will therefore provide critical information to understand how individuals' predictions shape sickness behavior, and how emotions are generated in infection-related conditions, which could open new therapies for mood disorders associated with immune activation.

Frågan om hur emotioner uppstår har gett upphov till många teorier. En ny och inflytelserik teori utgår från så kallad prediktiv kodning, som utgår från att hjärnan gör prediktioner (förutsägelse) som kontinuerligt jämförs med inkommande sensorisk information. När teorin om prediktiv kodning tillämpas inom emotionsområdet tros emotionella reaktioner uppstå när prediktionerna och de inre (interoceptiva) signalerna inte stämmer överens, dvs. när interoceptiva prediktionsfel föreligger. Teorin är relevant för känslomässiga störningar kopplade till infektioner (t.ex. postcovid), eftersom infektioner kan framkalla intensiva interoceptiva signaler som ibland är svåra att förutsäga för hjärnan. I detta projekt kommer vi att applicera denna teori i en infektionsmodell med bred ekologisk relevans för hälsa och med ett innovativt experimentellt tillvägagångsätt. Vi kommer att använda en experimentell modell av sjukdom för att framkalla riktiga sjukdomssymtom, samtidigt som vi direkt kommer att manipulera interoceptiva prediktionsfel, hos 240 deltagare. Vi förväntar oss att känslomässiga reaktioner kommer att uppstå vid sjukdom när interoceptiva prediktionsfel inträffar, dvs. när de interoceptiva signalerna skiljer sig från prediktionerna. Projektet kommer att bidra med kritisk kunskap för att förstå hur individers prediktioner formar sjukdomsbeteende och hur känslor genereras vid infektioner, vilket kan generera nya terapier för affektiva störningar associerade med immunaktivering.

Socioemotional perception is of importance for social and emotional function in humans everyday life. Previous neuroimaging studies have investigated socioemotional perception (e.g. of facial expressions) at a group level ignoring the fact this is an individual phenomena. Precision neuroimaging (PI) focus on single subjects and many repeated trials. Using PI to study human brain function associated with socioemotional perception is an unexplored territory.In this four years neuroimaging project we will scan 8 subjects during 15 scanning sessions. During scanning subject will be exposed to blocks of dynamic visual, auditory and visual-auditory socioemotional stimuli varying in valence (positive-negative) and arousal (high-low). A multivariate within-subject approach will be used including functional and structural brain data, subjective responses and various physiological measures. All analyses are conducted at the individual level, meaning that statistical models are fit separately to data from each participant. Standard functional and structural MRI data analysis methods will be used in combination with explorative AI approaches for identifying correlations within and between patterns of brain connectivity and behavioral outcome measures.This as a proof-of-concept project in the forefront of a coming paradigm shift in cognitive neuroscience which will eventually open new scientific venues and making it possible to conduct parallel animal research to get at neural mechanisms.