Host institution: University Hospital Essen, Germany

ESR10 – Contribution of the human cerebellum to fear learning: 7T fMRI studies in healthy human participants including pharmacological interventions

The human cerebellum is well known for its contribution to motor learning, and disorders in motor learning have been related to motor performance deficits in patients with cerebellar disease. The cerebellum is likely also involved in learning and memory processes in the cognitive and emotional domains, but this has been studied in much less detail. Our overarching aim is to get a fuller understanding of the contribution of the human cerebellum to learning and memory of fear, an important emotion for survival. To provide further evidence that the human cerebellum contributes to the different phases  of fear learning we will perform fear conditioning studies in healthy human participants in the 7T MRI scanner including pharmacological interventions. ESR10 and ESR13 will work closely together.

Young and healthy participants will perform fear conditioning tasks in the 7T MRI scanner. In part of the experiments dopaminergic and anti-dopaminergic drugs will be administered. To determine possible sex differences male and female participants will be tested. Differential fear conditioning will be performed using a 3-day design. fMRI analysis will be performed during the presentation, the prediction, and the unexpected omission of aversive signals. Fear conditioning paradigms will be harmonised between the three fMRI research groups involved in the ITN to aid comparison: Uppsala, Edinburgh and Essen. Resting state data will be acquired at the beginning of all fMRI experiments at each site to test whether strength of functional connectivity in emotional networks predicts behavioural outcome. Furthermore, MRI data analysis will be performed in close collaboration between the three 7T sites, and will include univariate and multivariate methods on reactivity/connectivity. Our group has performed structural and functional 7T MRI studies in healthy participants for many years with a focus on the cerebellum. A fear conditioning set-up in the 7T scanner is available. The findings will be compared with fMRI data in rodents (ESR11), and in patients with ataxias (ESR13) and anxiety disorders (ESR15). In collaboration with Bristol (ESR5) fMRI imaging and electrophysiological results will be compared in the medial and lateral cerebellum during fear conditioning in humans and rodents, respectively.

Experiments will provide further evidence that the human cerebellum contributes to learning in the emotional domain. We expect that different parts of the cerebellar cortex will be involved in fear learning, including more medial and lateral areas. More specifically, we expect that the unexpected omission of aversive signals, which is rewarding, will result in increased cerebellar activation reflecting processing of prediction errors. fMRI signals are expected to be modified by pharmacological interventions.

Planned secondments: Uppsala, month 13: training in multivariate fMRI analysis; Edinburgh, month 25: training in animal 7T MRI; Patrick Wild Centre, month 34, purpose: training in pre-clinical/clinical outreach.