The role of the cerebellum in feedback processing

While the cerebellum was long thought to be involved only in motor processes, there has recently been a paradigm shift that emphasizes its involvement in cognitive functions as well. However, the exact mechanisms are still unclear. The uniform neuroarchitecture of the cerebellum with closed, reciprocal, cerebello-cerebral loops suggests that the cerebellum fulfills similar functions across domains, e.g. timing, the generation of internal models and sequence detection. These functions can be embedded in a general concept of action monitoring or prediction and error-based learning. The present research program aims to investigate the role of the cerebellum in error and feedback processing. The experimental tasks also require prediction processes and test the dependence of these processes on feedback timing, so that the results are suitable for integrating different theories on the function of the cerebellum for cognitive processes. Specifically, the role of the cerebellum in the processing of and learning from immediate and delayed feedback will be investigated using complementary patient studies, electrophysiological measurements (EEG) and brain stimulation (single-pulse TMS) in healthy control subjects.

In addition to precise localization and quantification of the cerebellar-structural deficits, a comprehensive analysis of functional and structural connectivity is also planned for the patient studies. The planned research program is thus characterized by the use of a comprehensive, multimodal and conceptual approach.

In substudy 1, patients with progressive cerebellar degeneration and healthy control subjects will be tested with an EEG adaptation of a probabilistic learning task that includes immediate and delayed feedback. The extent and localization of cerebellar damage will be assessed by lesion-symptom mapping and functional and structural analysis and related to performance measures and neural response patterns.

Since these patients usually have rather diffuse cerebellar damage, patients with focal vascular lesions of the cerebellum and healthy control subjects with the same task are tested in sub-study 2. Due to the focality of the damage, conclusions about the significance of specific cerebellar subregions and circumscribed networks are better possible.

Sub-study 3 aims to elucidate temporal aspects of (causal) cerebellar involvement in the processing of and learning from immediate or delayed feedback using a “virtual lesion” approach. For this purpose, single-pulse TMS of the cerebellum or an extra-cerebellar control region (vertex) will be applied at different time points during task processing in healthy control subjects.