Abnormal regional brain function in Parkinson's disease: truth or fiction?

Normalization of regional measurements by the global mean is commonly employed to minimize inter-subject variability in functional imaging studies. This practice is based on the assumption that global values do not substantially differ between patient and control groups. Borghammer and colleagues challenge the validity of this assumption. They focus on Parkinson’s disease (PD) and use computer simulations to show that lower global values can produce spurious increases in subcortical brain regions. The authors speculate that the increased signal observed in these areas in PD patients is artifactual and unrelated to localized physiological changes in brain function. In this commentary, we summarize what is currently known of the relationship between regional and global metabolic activity in PD and experimental parkinsonism. Using SPM, we found that early PD patients demonstrated significant elevations in globally normalized metabolic activity localized to a discrete set of biologically relevant subcortical areas, despite virtually identical global metabolism in these patients and age-matched healthy controls. Group differences in the corresponding absolute measures were not detected because of their greater variability. Over time, abnormal increases in normalized (but not absolute) metabolic activity in subcortical regions appeared earlier in the course of disease and progressed faster than focal cortical reductions or declines in global values. These results indicate that subcortical elevations in normalized regional metabolism are not artifactual. In fact, these measures prove to be more sensitive than absolute values in detecting meaningful functional abnormalities in this disease. Multivariate analysis revealed that the abnormal spatial covariance structure of early PD is dominated by subcortical increases, which were not driven by reductions in cortical or global metabolic activity. Because of the stability of the network measurements, these indices are better suited for use as imaging biomarkers of PD progression and treatment efficacy.

在功能成像研究中，通常采用全局均值对区域测量值进行归一化，以尽量减少受试者间的变异性。这种做法基于这样一种假设，即患者组和对照组之间的全局值没有实质性差异。博尔哈默及其同事对这一假设的有效性提出了质疑。他们聚焦于帕金森病（PD），并通过计算机模拟表明，较低的全局值可能会导致皮质下脑区出现虚假的升高。作者推测，在帕金森病患者这些区域观察到的信号升高是人为的，与脑功能的局部生理变化无关。在这篇评论中，我们总结了目前对帕金森病和实验性帕金森综合征中区域和全局代谢活动之间关系的了解。利用统计参数映射（SPM），我们发现早期帕金森病患者在一组离散的具有生物学相关性的皮质下区域出现了全局归一化代谢活动的显著升高，尽管这些患者和年龄匹配的健康对照组的全局代谢几乎相同。由于相应的绝对测量值变异性较大，未检测到组间差异。随着时间的推移，皮质下区域归一化（而非绝对）代谢活动的异常升高在疾病进程中出现得更早，且比局灶性皮质降低或全局值下降进展得更快。这些结果表明，归一化区域代谢在皮质下的升高不是人为的。事实上，这些测量值在检测该疾病有意义的功能异常方面比绝对值更敏感。多变量分析显示，早期帕金森病异常的空间协方差结构主要由皮质下升高所主导，而不是由皮质或全局代谢活动的降低所驱动。由于网络测量的稳定性，这些指标更适合用作帕金森病进展和治疗效果的影像生物标志物。