Background: Impaired cortical inhibiton and maladaptive cortical plasticity are functional hallmarks of sporadic focal dystonias. Whether or not these mechanisms translate to generalized dystonias and whether these features reflect state or trait characteristics are topics of research in hereditary dystonias.
Methods: We present a series of studies using a multitracer approach with positron emission tomography (PET) and diffusion tensor MRI (DTI) in the DYT1 and the DYT6 genotype.
Results: In these hereditary dystonias functional and microstructural abnormalities were found in cortico-striatal-pallido-thalamocortical (CSPTC) and cerebellar-thalamo-cortical circuits. Genotype-specific abnormalities were localized to the basal ganglia, SMA and cerebellum. Functional changes, as potential correlates of maladaptive sensorimotor plasticity were found throughout the sensorimotor system and were more pronounced in affected mutation carriers than in their non-manifesting counterparts. In both genotypes, striatal metabolic abnormalities were paralleled by genotype-specific reductions in D2 receptor availability. However, these reductions failed to show a clear association with clinical or functional markers of the disease. By contrast, microstructural changes of cerebellar pathways clearly related to penetrance and may thus represent the main intrinsic abnormality underlying cortical downstream effects, such as increased sensorimotor responsivity.
Conclusions: These studies are consistent with the view of primary torsion dystonia as a neurodevelopmental circuit disorder involving CSPTC and related cerebellar pathways.