Cerebellar Contributions to Different Phases of Visceral Aversive Extinction Learning

Abstract

The cerebellum is increasingly recognized to contribute to non-motor functions, including cognition and emotion. Although fear conditioning has been studied for elucidating the pathophysiology of anxiety, the putative role of the cerebellum is still unknown. Fear conditioning could also be important in the etiology of chronic abdominal pain which often overlaps with anxiety. Hence, in this exploratory analysis, we investigated conditioned anticipatory activity in the cerebellum in a visceral aversive fear conditioning paradigm using functional magnetic resonance imaging. We extended and reanalyzed a previous dataset for different learning phases, i.e., acquisition, extinction, and reinstatement, utilizing an advanced normalizing method of the cerebellum. In 30 healthy humans, visual conditioned stimuli (CS(+)) were paired with painful rectal distensions as unconditioned stimuli (US), while other visual stimuli (CS(-)) were presented without US. During extinction, all CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. During acquisition, posterolateral cerebellar areas including Crus I, Crus II, and VIIb and parts of the dentate nucleus were activated in response to the CS(+) compared to the CS(-). During extinction, activation related to CS(+) presentation was detected in Crus I, Crus II, IV, V, VI, VIIb, IX, and vermis. Neural correlates of reinstatement were found in Crus I, Crus II, IV, V, and IX. We could show for the first time that the cerebellum is involved in abdominal pain-related associative learning processes. Together, these findings contribute to our understanding of the cerebellum in aversive learning and memory processes relevant to the pathophysiology of chronic abdominal pain.