The Role of Dopamine and Dopaminergic Pathways in Dystonia: Insights from Neuroimaging

BACKGROUND: Dystonia constitutes a heterogeneous group of movement abnormalities, characterized by sustained or intermittent muscle contractions causing abnormal postures. Overwhelming data suggest involvement of basal ganglia and dopaminergic pathways in dystonia. In this review, we critically evaluate recent neuroimaging studies that investigate dopamine receptors, endogenous dopamine release, morphology of striatum, and structural or functional connectivity in cortico-basal ganglia-thalamo-cortical and related cerebellar circuits in dystonia. METHOD: A PubMed search was conducted in August 2014. RESULTS: Positron emission tomography (PET) imaging offers strong evidence for altered D2/D3 receptor binding and dopaminergic release in many forms of idiopathic dystonia. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data reveal likely involvement of related cerebello-thalamo-cortical and sensory-motor networks in addition to basal ganglia. DISCUSSION: PET imaging of dopamine receptors or transmitter release remains an effective means to investigate dopaminergic pathways, yet may miss factors affecting dopamine homeostasis and related subcellular signaling cascades that could alter the function of these pathways. fMRI and DTI methods may reveal functional or anatomical changes associated with dysfunction of dopamine-mediated pathways. Each of these methods can be used to monitor target engagement for potential new treatments. PET imaging of striatal phosphodiesterase and development of new selective PET radiotracers for dopamine D3-specific receptors and Mechanistic target of rampamycin (mTOR) are crucial to further investigate dopaminergic pathways. A multimodal approach may have the greatest potential, using PET to identify the sites of molecular pathology and magnetic resonance methods to determine their downstream effects.