E-Appendix 1.

Image processing

All subjects participating in the PET study were also examined with a 1.5T MRI and axial T1 weighted three-dimensional spoiled GRASS images (SPGR, TE=7 ms, TR=23 ms, FOV=24 cm, flip angle 50°, 156 slice partitions of 1.2 mm thickness, 2 NEX).The MR images were realigned, resliced to 1 x 1 x 1 mm voxel size, and PET images were co-registered to the corresponding MR images using Statistical Parametric Mapping (SPM2) software (

Description of ROIs

The caudate and the putamen were delineated on three consecutive transaxial images, starting just at the appearance of the superior colliculi. The medial boundary for the putamen ROI was the internal capsule; the external capsule was the external border, and the superior boundary was defined by the corona radiata. The caudate ROI was bounded superiorly by the subcallosal fasciculus, its medial border was defined by the lateral ventricle, whereas the internal capsule defined the lateral boundary; the inferior border was the stria terminalis (Figure 2A). The cerebellum ROI was defined on three mid-PET sections, excluding the cerebellar peduncles and the vermis. The nigra, as well as the midbrain ROIs were delineated on three horizontal sections, first on the MR images and then on the corresponding PET images. The upper slice was defined on the plane showing the mamillary bodies and the optic nerves, the lower border was at the level of the middle cerebellar peduncle. The left and right substantia nigra were defined on the same sections, using 6mm circles (Figure 2B). The DA containing substantia nigra is a small region, and use of small ROIs implies risk of noise and partial volume effects. Therefore, in addition to the nigra, we also delineated a midbrain ROI (Figure 2 C-D), excluding the superior and inferior colliculi, but comprising the substantia nigra and the dopamine containing ventral tegmentum (Figure 2C).