ESR13

Host institution: University Hospital Essen, Germany

ESR13 – Contribution of the human cerebellum to fear learning: 7T fMRI studies in patients with cerebellar degeneration

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 fear learning we will perform fear conditioning studies in patients with cerebellar degeneration in the 7T MRI scanner. ESR10 and ESR13 will work closely together.

Patients with cerebellar cortical degeneration and age- and sex-matched controls will be tested in a 7T Magnetom Terra MR scanner. Differential fear conditioning will be performed using a 3-day design. fMRI activity will be assessed in the CS-US time window (to assess fMRI activity related to prediction of the US), and, equally important, at the time the US is expected but does not occur (in interspersed CS-only and initial extinction trials; to assess prediction error). fMRI analysis will include functional connectivity analysis between the cerebellum and other brain areas involved in fear conditioning. Behavioural studies will be complemented by testing an approach-avoidance paradigm in patients with cerebellar degeneration in close collaboration with the group in Uppsala. The host group has extensive experience of structural and functional 7T MR imaging in patients with cerebellar degeneration and healthy participants, and has a well-established ataxia clinic for patient recruitment. A fear conditioning set-up in the 7T scanner is available. 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. The findings will be compared with fMRI data in rodents (ESR11), and in patients with ataxias (ESR13) and anxiety disorders (ESR15).

Experiments will provide further evidence that the human cerebellum contributes to learning in the emotional domain. Experiments will allow a fuller understanding of the interactions between the cerebellum and the known fear acquisition and extinction networks. Furthermore, close collaboration between the three MRI sites in the ITN will allow a comprehensive understanding of changes in emotional networks not only in cerebellar disease, but also neurodevelopmental and anxiety disorders, an important prerequisite to develop future treatments.

Planned secondments: Rehab Kettwig, month 7,19, purpose: patient acquisition; Uppsala, month 28, purpose: training in fMRI analysis.