North Florida/South Georgia Veterans Health System, Gainesville, FL, USA; Department of Psychiatry, University of Florida, Gainesville, FL, USA; Department of Psychology, University of Florida, Gainesville, FL, USA.
Department of Statistics, University of Florida, Gainesville, FL, USA.
Neuroimage. 2013 Nov 1;81:484-495. doi: 10.1016/j.neuroimage.2011.07.012. Epub 2011 Jul 14.
Apathy and depression are heterogeneous syndromes with symptoms that overlap clinically. This clinical overlap leads to problems with classification and diagnosis in clinical populations. No functional imaging study has attempted to separate brain regions altered in apathy from those altered in depression in a clinical population. Parkinson disease (PD) is a disorder in which apathy and depression co-exist in a single population. We evaluate the relationship between apathy, depression, and motor severity of disease in PD, focusing on the relationship between these factors and the amplitude of the low frequency fluctuation (ALFF) in the resting state. We first evaluated if the resting ALFF signal is a reliable measure for our clinical question. For this, we develop and introduce a cross validation approach we term the "Regional Mapping of Reliable Differences" (RMRD) method to evaluate reliability of regions of interest deemed "significant" by standard voxel-wise techniques. Using this approach, we show that the apathy score in this sample is best predicted by ALFF signal in the left supplementary motor cortex, the right orbitofrontal cortex, and the right middle frontal cortex, whereas depression score is best predicted by ALFF signal in the right subgenual cingulate. Disease severity was best predicted by ALFF signal in the right putamen. A number of additional regions are also statistically (but not reliably) correlated with our neuropsychological measures and disease severity. Our results support the use of resting fMRI as a means to evaluate neuropsychiatric states and motor disease progression in Parkinson disease, and the clinical and epidemiologic observation that apathy and depression are distinct pathological entities. Our finding that "significance" and "reliability" are dissociated properties of regions of interest identified as significant using standard voxel-wise techniques suggests that including reliability analyses may add useful scientific information in neurobehavioral research.
冷漠和抑郁是具有临床症状重叠的异质综合征。这种临床重叠导致临床人群在分类和诊断方面存在问题。没有功能影像学研究试图在临床人群中分离出冷漠和抑郁改变的脑区。帕金森病（PD）是一种在单一人群中同时存在冷漠和抑郁的疾病。我们评估了 PD 中冷漠、抑郁和疾病运动严重程度之间的关系，重点关注这些因素与静息状态下低频波动幅度（ALFF）之间的关系。我们首先评估静息 ALFF 信号是否是我们临床问题的可靠测量指标。为此，我们开发并引入了一种交叉验证方法，我们称之为“区域可靠差异映射”（RMRD）方法，以评估被标准体素技术认为“显著”的感兴趣区域的可靠性。使用这种方法，我们表明，在这个样本中，冷漠评分最好由左侧辅助运动皮层、右侧眶额皮层和右侧中间额皮层的 ALFF 信号预测，而抑郁评分最好由右侧扣带回下皮质的 ALFF 信号预测。疾病严重程度最好由右侧壳核的 ALFF 信号预测。还有一些额外的区域与我们的神经心理学测量和疾病严重程度也存在统计学上（但不可靠）的相关性。我们的研究结果支持使用静息 fMRI 来评估帕金森病中的神经精神状态和运动疾病进展，并支持临床和流行病学观察，即冷漠和抑郁是不同的病理实体。我们发现，“显著性”和“可靠性”是使用标准体素技术识别的显著感兴趣区域的分离属性，这表明包括可靠性分析可能会为神经行为研究增加有用的科学信息。
