Altered striatal and pallidal connectivity in cervical dystonia

Abstract

Cervical dystonia is a neurological movement disorder characterized by involuntary, abnormal movements of the head and neck. Injecting the overactive muscles with botulinum toxin is the gold standard treatment, supported by good evidence (Delnooz and van de Warrenburg in Ther Adv Neurol Disord 5:221-240, 2012). Current views on its pathophysiology support a role for the basal ganglia, although there are probably more widespread abnormalities in brain networks in which the basal ganglia are important nodes. Their precise role in cervical dystonia is unknown. We sought to address this issue by examining alterations in the functional connectivity of the basal ganglia. Using resting-state functional MRI and functional parcellations, we investigated functional connectivity in cervical dystonia patients and age- and gender-matched healthy controls. We mapped connectivity voxel-wise across the striatum and the globus pallidus for a set of brain masks, defined from well-known resting-state networks. Scans were repeated before and after botulinum toxin injections to see whether connectivity abnormalities were perhaps restored. We found that in cervical dystonia (1) the right mid-dorsal putamen and right external globus pallidus have reduced connectivity with a network comprising left fronto-parietal regions; and (2) the bilateral anterior putamen shows a trend towards enhanced connectivity with a network comprising sensorimotor areas. We observed that botulinum toxin treatment induces reorganization between a network comprising mainly (pre)frontal areas and (1) the right mid-ventral striatum and (2) the right external globus pallidus. Cervical dystonia patients have altered functional connectivity between the basal ganglia and some cortical regions that are part of specific brain networks that in part are influenced by botulinum toxin treatment. These connectivity abnormalities may be primary as well as secondary, perhaps compensatory, phenomena.