Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada; Brain Health Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Schizophr Res. 2022 Oct;248:21-31. doi: 10.1016/j.schres.2022.07.012. Epub 2022 Jul 28.
Heterogeneity has been a persistent challenge in understanding Schizophrenia Spectrum Disorders (SSD). Traditional case-control comparisons often show variable results, and may not map well onto individuals. To better understand heterogeneity and group differences in SSD compared to typically developing controls (TDC), we examined variability in functional brain activity during a working memory (WM) task with known deficits in SSD. Neuroimaging and behavioural data were extracted from two datasets collectively providing 34 TDC and 56 individuals with SSD (n = 90). Functional activity in response to an N-Back WM task (3-Back vs 1-Back) was examined between and within groups. Individual variability was calculated via the correlational distance of fMRI activity maps between participants; mean correlational distance from one participant to all others was defined as a 'variability score'. Greater individual variability in functional activity was found in SSD compared to TDC (p = 0.00090). At the group level, a case-control comparison suggested SSD had reduced activity in task positive and task negative networks. However, when SSD were divided into high and low variability subgroups, the low variability groups showed no differences relative to TDC while the high variability group showed little activity at the group level. Our results imply prior case-control differences may be driven by a subgroup of SSD who do not show specific impairments but instead show more 'idiosyncratic' activity patterns. In SSD but not TDC, variability was also related to cognitive performance and age. This novel approach focusing on individual variability has important implications for understanding the neurobiology of SSD.
精神分裂症谱系障碍（SSD）的异质性一直是一个难以理解的问题。传统的病例对照比较通常会产生不同的结果，而且可能与个体差异不匹配。为了更好地理解 SSD 与典型发育对照（TDC）之间的异质性和组间差异，我们检查了在工作记忆（WM）任务中功能性大脑活动的变异性，该任务在 SSD 中存在已知缺陷。从两个数据集共提取了神经影像学和行为学数据，共提供了 34 名 TDC 和 56 名 SSD 个体（n=90）。在组间和组内检查了对 N-Back WM 任务（3-Back 与 1-Back）的功能活性。通过参与者之间的 fMRI 活动图的相关距离来计算个体变异性；将一个参与者与所有其他参与者的平均相关距离定义为“变异性得分”。与 TDC 相比，SSD 中的功能活动个体变异性更大（p=0.00090）。在组水平上，病例对照比较表明 SSD 在任务正性和任务负性网络中的活性降低。但是，当 SSD 分为高变异性亚组和低变异性亚组时，低变异性组与 TDC 相比没有差异，而高变异性组在组水平上几乎没有活性。我们的结果表明，先前的病例对照差异可能是由一组 SSD 引起的，这些 SSD 没有表现出特定的损伤，而是表现出更多的“特殊”活动模式。在 SSD 中，但不在 TDC 中，变异性与认知表现和年龄也有关系。这种关注个体变异性的新方法对理解 SSD 的神经生物学具有重要意义。
