Department of Neuroscience and Experimental Therapeutics, Albany Medical College, Albany, NY, USA.
GE Global Research Center, Niskayuna, NY, USA.
Neuromodulation. 2020 Jun;23(4):515-524. doi: 10.1111/ner.13160. Epub 2020 May 5.
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.
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.
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.
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).
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.
深部脑刺激（DBS）是一种被广泛接受的治疗帕金森病（PD）的方法。运动表型包括震颤为主型（TD）、运动不能-强直型（AR）和姿势不稳步态障碍型（PIGD）。DBS 调节运动症状缓解的作用机制尚不清楚。
采用血氧水平依赖（BOLD）功能磁共振成像（fMRI）来确定 DBS 是否根据 PD 表型改变运动症状的功能活动。
受试者进行 fMRI 扫描，记录 DBS 循环开启和关闭时的 BOLD 激活情况。通过体素分析记录每个表型的 DBS 循环对 BOLD 激活的影响。对于每个感兴趣区域，采用 T 值进行方差分析，并进行协变量分析。进一步，对刺激设置与 T 值进行相关性分析。最后，比较运动改善和恶化的患者的 T 值。
作为一个整体，DBS-ON 时 BOLD 激活导致运动丘脑（p < 0.01）和外苍白球（p < 0.01）激活。与 PIGD（p < 0.01）和 TD 组（p < 0.01）相比，AR 患者的辅助运动区（SMA）激活更多。此外，AR 组的运动皮层（MI）比 TD 组（p = 0.02）激活更多。植入核（p = 0.01）和表型（p < 0.01）影响 MI 活动，而表型单独影响 SMA 活动（p < 0.01）。丘脑激活与脉宽呈正相关（p = 0.03），尾状核与总电能输送呈正相关（p = 0.04）。
这些数据表明，DBS 根据患者的运动表型不同调节网络活动。进一步了解这些差异可能有助于我们深入了解 DBS 对 PD 运动症状的作用机制，并优化治疗。
