Freiburg Brain Imaging, University of Freiburg, Freiburg, Germany; Port d'Informació Científica (PIC), Campus UAB Edifici D, Bellaterra, Spain.
Psychiatry Res. 2013 Dec 30;214(3):322-30. doi: 10.1016/j.pscychresns.2013.09.009. Epub 2013 Oct 6.
The early, preferably pre-clinical, identification of neurodegenerative diseases is important as treatment will be most successful before substantial neuronal loss. Here, we reasoned that functional brain changes as measured using functional magnetic resonance imaging (fMRI) will precede neurodegeneration. Three independent cohorts of patients with the genetic mutation leading to Huntington's Disease (HD) but without any clinical symptoms and matched controls performed three different fMRI tasks: Sequential finger tapping engaged the motor system, which is primarily affected by HD, whereas a working-memory task and a task aiming to induce irritation represented the range of low- and high-level cognitive functions also affected by HD. Each diagnostic group of every cohort included 11-16 subjects. After segmentation into 76 cortical and 14 subcortical regions, we extracted functional connectivity patterns through pairwise correlation between the signals in the regions. The resulting coefficients were directly embedded as input to a pattern classifier aiming to separate controls from gene mutation carriers. Alternatively, graph-theory measures such as degree and clustering coefficient were used as features for the discrimination. Classification accuracy never outperformed the accuracy of a grouping based on parameter estimates from a general-linear model approach or a grouping based on features extracted from anatomical images as reported in a previous analysis. Despite good within-subject stability between two runs of the same task, a high between-subject variability led to chance-level accuracy. These results indicate that standard graph-metrics are insufficient to detect subtle disease related changes when within-group variability is high. Developing methods that reduce variability related to noise should be the focus of future studies.
早期,最好是临床前,识别神经退行性疾病很重要,因为在大量神经元丢失之前进行治疗将最成功。在这里,我们推断使用功能磁共振成像 (fMRI) 测量的功能性大脑变化将先于神经退行性变。三个独立的亨廷顿病 (HD) 遗传突变患者队列,没有任何临床症状,并且与对照组相匹配,进行了三项不同的 fMRI 任务:顺序手指敲击涉及运动系统,这主要受 HD 影响,而工作记忆任务和旨在引起刺激的任务则代表了受 HD 影响的低水平和高水平认知功能的范围。每个队列的每个诊断组都包括 11-16 名受试者。在将大脑皮层分为 76 个区域和 14 个皮质下区域,并将信号分段为 76 个皮质和 14 个皮质下区域后,通过对区域之间的信号进行成对相关,提取功能连接模式。所得系数直接作为输入嵌入到模式分类器中,该分类器旨在将对照组与基因突变携带者区分开来。或者,将诸如度和聚类系数等图论度量用作区分特征。分类精度从未超过基于一般线性模型方法的参数估计或基于以前分析中从解剖图像提取的特征的分组的精度。尽管相同任务的两次运行之间具有良好的受试者内稳定性,但受试者间的高度变异性导致了偶然的准确性。这些结果表明,当组内变异性较高时,标准图度量不足以检测与疾病相关的细微变化。开发可降低与噪声相关的变异性的方法应成为未来研究的重点。