Sperling Scott A, Druzgal Jason, Blair Jamie C, Flanigan Joseph L, Stohlman Shelby L, Barrett Matthew J
Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Radiology and Medical Imaging, University of Virginia, Charlottesville, VA, USA.
Clin Neuropsychol. 2023 Apr;37(3):676-694. doi: 10.1080/13854046.2022.2065362. Epub 2022 Apr 21.
The generation and maintenance of goal-directed behavior is subserved by multiple brain regions that receive cholinergic inputs from the cholinergic nucleus 4 (Ch4). It is unknown if Ch4 degeneration contributes to apathy in Parkinson's disease (PD). We analyzed data from 106 pre-surgical patients with PD who had brain MRIs and completed the Frontal Systems Behavior Scales (FrSBe). Eighty-eight patients also completed the Beck Depression Inventory-2nd Edition. Cholinergic basal forebrain grey matter densities (GMD) were measured by applying probabilistic maps to T1 MPRAGE sequences processed using voxel-based morphometry methods. We used linear and hierarchical regression modelling to examine the association between Ch4 GMD and the FrSBe Apathy subscale scores. We used similar methods to assess the specificity of this association and potential associations between Ch4 target regions and apathy. Ch4 GMD ( = .021) and Ch123 GMD ( = .032) were significantly associated with Apathy subscale scores on univariate analysis. Ch4 GMD, but not Ch123 GMD, remained significantly associated with apathy when adjusting for age, sex, levodopa equivalent doses, and disease duration. Centromedial amygdala GMD, which receives cholinergic inputs from Ch4, was also associated with apathy. Ch4 GMD was not associated with depression or disinhibition, nor was it associated with executive dysfunction when adjusting for clinical and demographic variables. Ch4 GMD is specifically associated with apathy in PD. Ch4 degeneration results in cholinergic denervation of multiple cortical and limbic regions, which may contribute to the cognitive and emotional-affective processing deficits that underlie the behavioral symptoms of apathy.
目标导向行为的产生和维持由多个接受来自胆碱能核4（Ch4）胆碱能输入的脑区所支持。尚不清楚Ch4变性是否导致帕金森病（PD）中的冷漠。我们分析了106例接受手术前的PD患者的数据，这些患者进行了脑部MRI检查并完成了额叶系统行为量表（FrSBe）。88例患者还完成了贝克抑郁量表第二版。通过将概率图谱应用于使用基于体素的形态计量学方法处理的T1 MPRAGE序列来测量胆碱能基底前脑灰质密度（GMD）。我们使用线性和分层回归模型来检查Ch4 GMD与FrSBe冷漠分量表得分之间的关联。我们使用类似的方法来评估这种关联的特异性以及Ch4靶区域与冷漠之间的潜在关联。在单变量分析中，Ch4 GMD（=0.021）和Ch123 GMD（=0.032）与冷漠分量表得分显著相关。在调整年龄、性别、左旋多巴等效剂量和病程后，Ch4 GMD而非Ch123 GMD仍与冷漠显著相关。接受来自Ch4胆碱能输入的中央内侧杏仁核GMD也与冷漠相关。在调整临床和人口统计学变量后，Ch4 GMD与抑郁或去抑制无关，也与执行功能障碍无关。Ch4 GMD与PD中的冷漠特异性相关。Ch4变性导致多个皮质和边缘区域的胆碱能去神经支配，这可能导致作为冷漠行为症状基础的认知和情感加工缺陷。
