Functional and structural connectivity between the cerebellum and the cortical mirror neuron system: evidence from fMRI and DTI probabilistic tractography

Studies in humans and monkeys have shown that action observation activates not only cortical areas of the mirror neuron system (MNS) but also the cerebellum and other subcortical structures. Cortico-cerebellar circuits are proposed to be involved in the predictive control and simulation of goal-directed observed actions. However, it remains unclear whether cerebellar projections originating from visuo-motor sectors are partially segregated from those starting from purely motor sectors. To address this issue, sixteen healthy participants underwent an fMRI study in which they were required to observe and execute grasping actions. The study allowed to identify cerebellar and thalamic regions predominantly involved in motor execution, as well as regions activated during both observation and execution. Probabilistic tractography and effective connectivity analyses were then used to characterize the projections and functional interactions of these sectors. The cerebellar lobules I-V, dorsal dentate nucleus (DN) and ventrolateral-ventral anterior thalamic nuclei (VL-VA) were mainly active during execution, whereas cerebellar lobule VI, ventral DN, red nucleus (RN) and ventroposterolateral thalamic nucleus (VPL) showed shared activation during observation and execution. At the cortical level, both observation and execution engaged the ventral premotor cortex (PMv) and the inferior parietal lobule (IPL). Tractography revealed that dorsal DN tracts project to RN and VL-VA, terminating in rostral IPL and ventral PMv, while ventral DN projections target RN and VPL, terminating more caudally in IPL and more dorsally in PMv. Effective connectivity analyses showed that execution was associated with increased coupling between DN, RN, VL-VA, and IPL-PMv, while both observation and execution were characterized by enhanced connectivity between DN, RN, VPL, and IPL-PMv. Overall, these findings indicate that cerebellar projections to thalamic and cortical regions involved in action observation and execution are partially segregated from purely motor projections, supporting a cerebellar role in motor simulation during observation and execution of goal-directed actions.