Coordinate based meta-analysis of motor functional imaging in Parkinson's: disease-specific patterns and modulation by dopamine replacement and deep brain stimulation

Objective To investigate factors affecting the pattern of motor brain activation reported in people with Parkinson's (PwP), aiming to differentiate disease-specific features from treatment effects. Methods A co-ordinate-based-meta-analysis (CBMA) of functional motor neuroimaging studies involving patients with Parkinson's (PwP), and healthy controls (HC) identified 126 suitable articles. The experiments were grouped based on subject feature, medication status (onMed/offMed), deep brain stimulation (DBS) status (DBSon/DBSoff) and type of motor initiation. Results HC and PwP shared similar neural networks during upper extremity motor tasks but with differences of reported frequency in mainly bilateral putamen, insula and ipsilateral inferior parietal and precentral gyri. The activation height was significantly reduced in the bilateral putamen, left SMA, left subthalamus nucleus, right thalamus and right midial global pallidum in PwP(offMed)(vs. HC), and pre-SMA hypoactivation correlated with disease severity. These changes were not found in patients on dopamine replacement therapy (PwP(onMed)vs. HC) in line with a restorative function. By contrast, left SMA and primary motor cortex showed hyperactivation in the medicated state (vs. HC) suggesting dopaminergic overcompensation. Deep-brain stimulation (PwP during the high frequency subthalamus nucleus (STN) DBS vs. no stimulation) induced a decrease in left SMA activity and the expected increase in the left subthalamic/thalamic region regardless of hand movement. We further demonstrated a disease related effect of motor intention with only PwP(offMed)showing increased activation in the medial frontal lobe in self-initiated studies. Conclusion We describe a consistent disease-specific pattern of putaminal hypoactivation during motor tasks that appears reversed by dopamine replacement. Inconsistent reports of altered SMA/pre-SMA activation can be explained by task- and medication-specific variation in intention. Moreover, SMA activity was reduced during STN-DBS, while dopamine-induced hyperactivation of SMA which might underpin hyperdynamic L-dopa related overcompensation.