Brain dopaminergic (FluroDOPA PET) correlates of kinematic flexibility in Parkinson's Disease

Objective: To evaluate the correlation of kinematic parameters of upper limb motor performance with brain dopaminergic function in Parkinson's disease (PD). Background: By means of 6-[18F]fluoro-l-dopa (FluoroDOPA) positron emission tomography (PET) both nigrostriatal and extra-nigrostriatal dopaminergic function can be imaged in PD. When compared to normal controls, PD patients present a reduced flexibility in selecting the time required to perform movements to predictable versus unpredictable targets. This has been related to a reduced kinematic flexibility and involvement of the direct pathway (Moisello C et al. Parkinsonism Relat Disord. 2011;17:642-4), however this peculiar phenomenon needs to be further investigated. Methods: Fifteen drug-naïve, de novo PD patients were recruited (3 females, mean age 67 years, range 60-76). Patients underwent clinical staging with Hoehn&Yahr and UPDRS scales, brain MRI, extensive neuropsychological assessment, FluoroDOPA brain PET and kinematic study involving a digitized tablet where patients had to perform reaching movements to one of 8 radial targets displayed on a computer screen. Two different motor paradigms have been performed: 1) RAN - targets appeared in an unpredictable order and instructions were to reach the target as soon as possible, 2) CCW - targets appeared in a predictable order and patients had to reach them without specific constrains. Results: Indexes of motor performance such as reaction time, movement time, spatial accuracy in reaching the target were computed. The difference between the time required to reach the target in the CCW and the RAN conditions was also computed (delta-MT; Moisello et al, 2011). No significant correlation was found between FluoroDOPA uptake and reaction time, movement time and spatial accuracy. A significant direct correlation (p<0.001 uncorrected at voxel level; p<0.05 FDR-corrected at cluster level by means of SPM8) was found between delta-MT and FluoroDOPA uptake in the lateral temporal cortex (Brodmann area 22) of the less affected hemisphere. Conclusions: Our data try to contribute in understanding the novel concept of kinematic flexibility in PD and point to the involvement of lateral temporal cortex in this peculiar function in early PD.