From gut feelings to memories of interoceptive pain: Associative learning and extinction of conditioned threat predictors across sensory modalities

Description: The formation and persistence of negative pain-related expectations by classical conditioning remain incompletely understood. We elucidated behavioural and neural correlates involved in the acquisition and extinction of negative expectations towards different threats across sensory modalities. In two complementary functional magnetic resonance imaging studies in healthy humans (data of the final sample of N=65 provided) , differential conditioning paradigms combined interoceptive visceral pain with somatic pain (study 1; N=42) and aversive tone (study 2; N=23) as exteroceptive threats. Conditioned responses to interoceptive threat predictors were enhanced in both studies, consistently involving the insula and cingulate cortex. Interoceptive threats had a greater impact on extinction efficacy, resulting in a disruption of ongoing extinction (study 1), or even in a selective resurgence of the interoceptive CS-US association after complete extinction (study 2). In the face of multiple threats, we preferentially learn, store, and remember interoceptive danger signals. As key mediators of nocebo effects, conditioned responses may be particularly relevant to clinical conditions involving disturbed interoception and chronic visceral pain. Notes: 1) Two data sets were analyzed for the purpose of this manuscript (study1; study2) . All analyses performed are uploaded and named in different folders for all learning phases (acquisition (ACQ); extinction (EXT); reinstatement (RST)) and studies separately. 2) Scanner settings identical to both studies are provided in the respective fields. Separate settings are as follows: study 1: TR 2300ms, FOV 220 x 220mm2, matrix 94 x 94mm2; study 2: TR 2400ms, FOV 240 x 240mm2, matrix 104 x 104mm2.

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