Activity and connectivity of the cerebellum in trigeminal nociception

The role of the cerebellum in pathologies of the trigeminal nervous system is still unknown although recently gathered evidence point to a modulatory rather than a passive role. Here we provide evidence for the activation of specific cerebellar areas during nociceptive trigeminal input in the left nostril in a large number of volunteers (54 subjects) and an additional independent group (18 subjects) as measured by functional magnetic resonance imaging (fMRI). Peak voxel activity ipsilateral to the stimulated side can be seen in cerebellar lobules VI, VIIIa and Crus I, and vermal lobule VIIIa, although some activations are also seen in the contralateral side. The individuals' intensity and unpleasantness ratings are mostly processed in the hemispheric lobules VI stretching to V, representing the face areas of the cerebellar's fractured homunculus. We found a robust functional connectivity during nociception between the cerebellum and the rostral part of the pons as well as the periaqueductal grey and the thalamus, involving the descending antinociceptive network as well as areas known to form close loops with the cerebellum in the motor domain. Cerebellar connectivity with higher cortical areas include most of the known hubs in pain processing which are the insular cortex, operculum and putamen, and the face areas in the precentral gyrus. The current data provide a solid basis for further research of the cerebellar's activity and connectivity in primary headache and facial pain syndromes.