Cause or effect: Altered brain and network activity in cervical dystonia is partially normalized by botulinum toxin treatment

Background Idiopathic cervical dystonia (CD) is a chronic movement disorder characterized by impressive clinical symptoms and the lack of clear pathological findings in clinical diagnostics and imaging. At present, the injection of botulinum toxin (BNT) in dystonic muscles is an effective therapy to control motor symptoms and pain in CD. Objectives We hypothesized that, although it is locally injected to dystonic muscles, BNT application leads to changes in brain and network activity towards normal brain function. Methods Using 3 T functional MR imaging along with advanced analysis techniques (functional connectivity, Granger causality, and regional homogeneity), we aimed to characterize brain activity in CD (17 CD patients vs. 17 controls) and to uncover the effects of BNT treatment (at 6 months). Results In CD, we observed an increased information flow within the basal ganglia, the thalamus, and the sensorimotor cortex. In parallel, some of these structures became less responsive to regulating inputs. Furthermore, our results suggested an altered somatosensory integration. Following BNT administration, we noted a shift towards normal brain function in the CD patients, especially within the motor cortex, the somatosensory cortex, and the basal ganglia. Conclusion The changes in brain function and network activity in CD can be interpreted as related to the underlying cause, the effort to compensate or a mixture of both. Although BNT is applied in the last stage of the cortico-neuromuscular pathway, brain patterns are shifted towards those of healthy controls.
Highlights • we characterized brain activity in CD and the effects of BNT using 3T fMR imaging and network analysis techniques • following treatment with botulinum toxin (BNT), abnormal brain activity patterns in primary dystonia are attenuated • critical key regions for both the pathophysiology and BNT-induced improvement in cervical dystonia are the BG