Disrupted Functional Connectivity of Basal Ganglia across Tremor-Dominant and Akinetic/Rigid-Dominant Parkinson's Disease

It is well known that disruption of basal ganglia function generates the motor symptoms in PD, however, these are presented in a heterogeneous manner; patients can be divided into tremor-dominant and akinesia/rigidity-dominant subtypes. To date, it is unknown if these differences in the motor symptoms could be explained by differences on the functional connectivity of basal ganglia with specific brain regions. In this study, we aimed to explore the alterations of the network-based and global functional connectivity linking to basal ganglia between the PD-TD and PD-AR patients. One hundred and six PD patients and 52 normal controls were recruited. According to the subscales of UPDRS motor scale, PD patients were divided into the PD-TD (n = 57) and PD-AR (n = 49) subtypes. We performed independent component analysis to identify basal ganglia network (BGN) involving connected brain regions having coactivation with basal ganglia. Eigenvector centrality mapping were processed and the eigenvector centrality in the subcortical component of BGN including the bilateral caudate nuclei, putamen, thalami and pallidum were extracted to measure the global connectivity. Compared with controls, whole PD patients or PD subtypes showed decreases of functional connectivity within the subcortical component of BGN, e.g., thalamus, pallidum and putamen. Compared with controls, decreased functional connectivity of precuneus and amygdala with basal ganglia was observed in the PD-TD while that of occipital lobule and precuneus was observed in the PD-AR. Compared with the PD-TD, significantly decreased functional connectivity between occipital lobule and cerebellum posterior lobule and basal ganglia was observed in the PD-AR, and such connectivity had positive correlations with tremor and negative correlations with akinesia/rigidity. We also observed enhanced global connectivity in the caudate nucleus and thalamus in the PD subtypes compared with controls. In conclusion, PD patients independent of motor subtypes consistently express similar alterations of functional connectivity within the subcortical component of BGN including network-based connectivity and global connectivity. Functional connectivity of cerebellum posterior lobule and occipital lobule with basal ganglia play important roles in the modulation of parkinsonian motor symptoms.