Multimodal neuroimaging to characterize symptom-specific networks in movement disorders

Movement disorders, such as Parkinson's disease, essential tremor, and dystonia, are characterized by their predominant motor symptoms, yet diseases causing abnormal movement also encompass several other symptoms, including non-motor symptoms. Here we review recent advances from studies of brain lesions, neuroimaging, and neuromodulation that provide converging evidence on symptom-specific brain networks in movement disorders. Although movement disorders have traditionally been conceptualized as disorders of the basal ganglia, cumulative data from brain lesions causing parkinsonism, tremor and dystonia have now demonstrated that this view is incomplete. Several recent studies have shown that lesions causing a given movement disorder occur in heterogeneous brain locations, but disrupt common brain networks, which appear to be specific to each motor phenotype. In addition, findings from structural and functional neuroimaging in movement disorders have demonstrated that brain abnormalities extend far beyond the brain networks associated with the motor symptoms. In fact, neuroimaging findings in each movement disorder are strongly influenced by the constellation of patients' symptoms that also seem to map to specific networks rather than individual anatomical structures or single neurotransmitters. Finally, observations from deep brain stimulation have demonstrated that clinical changes, including both symptom improvement and side effects, are dependent on the modulation of large-scale networks instead of purely local effects of the neuromodulation. Combined, this multimodal evidence suggests that symptoms in movement disorders arise from distinct brain networks, encouraging multimodal imaging studies to better characterize the underlying symptom-specific mechanisms and individually tailor treatment approaches.