Use of Functional Magnetic Resonance Imaging to Assess How Motor Phenotypes of Parkinson's Disease Respond to Deep Brain Stimulation.

BACKGROUND: Deep brain stimulation (DBS) is a well-accepted treatment of Parkinson's disease (PD). Motor phenotypes include tremor-dominant (TD), akinesia-rigidity (AR), and postural instability gait disorder (PIGD). The mechanism of action in how DBS modulates motor symptom relief remains unknown. OBJECTIVE: Blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) was used to determine whether the functional activity varies in response to DBS depending on PD phenotypes. MATERIALS AND METHODS: Subjects underwent an fMRI scan with DBS cycling ON and OFF. The effects of DBS cycling on BOLD activation in each phenotype were documented through voxel-wise analysis. For each region of interest, ANOVAs were performed using T-values and covariate analyses were conducted. Further, a correlation analysis was performed comparing stimulation settings to T-values. Lastly, T-values of subjects with motor improvement were compared to those who worsened. RESULTS: As a group, BOLD activation with DBS-ON resulted in activation in the motor thalamus (p < 0.01) and globus pallidus externa (p < 0.01). AR patients had more activation in the supplementary motor area (SMA) compared to PIGD (p < 0.01) and TD cohorts (p < 0.01). Further, the AR cohort had more activation in primary motor cortex (MI) compared to the TD cohort (p = 0.02). Implanted nuclei (p = 0.01) and phenotype (p = <0.01) affected activity in MI and phenotype alone affected SMA activity (p = <0.01). A positive correlation was seen between thalamic activation and pulse-width (p = 0.03) and between caudate and total electrical energy delivered (p = 0.04). CONCLUSIONS: These data suggest that DBS modulates network activity differently based on patient motor phenotype. Improved understanding of these differences may further our knowledge about the mechanisms of DBS action on PD motor symptoms and to optimize treatment.

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.