Section on Advanced Functional Neuroimaging, Brain Imaging Center,
Emotion and Development Branch.
J Neurosci. 2018 Apr 4;38(14):3559-3570. doi: 10.1523/JNEUROSCI.1864-17.2018. Epub 2018 Feb 27.
Age-related changes in human functional neuroanatomy are poorly understood. This is partly due to the limits of interpretation of standard fMRI. These limits relate to age-related variation in noise levels in data from different subjects, and the common use of standard adult brain parcellations for developmental studies. Here we used an emerging MRI approach called multiecho (ME)-fMRI to characterize functional brain changes with age. ME-fMRI acquires blood oxygenation level-dependent (BOLD) signals while also quantifying susceptibility-weighted transverse relaxation time (T*) signal decay. This approach newly enables reliable detection of BOLD signal components at the subject level as opposed to solely at the group-average level. In turn, it supports more robust characterization of the variability in functional brain organization across individuals. We hypothesized that BOLD components in the resting state are not stable with age, and would decrease in number from adolescence to adulthood. This runs counter to the current assumptions in neurodevelopmental analyses of brain connectivity that the number of BOLD signal components is a random effect. From resting-state ME-fMRI of 51 healthy subjects of both sexes, between 8.3 and 46.2 years of age, we found a highly significant ( = -0.55, ≪ 0.001) exponential decrease in the number of BOLD components with age. The number of BOLD components were halved from adolescence to the fifth decade of life, stabilizing in middle adulthood. The regions driving this change were dorsolateral prefrontal cortices, parietal cortex, and cerebellum. The functional network of these regions centered on the cerebellum. We conclude that an age-related decrease in BOLD component number concurs with the hypothesis of neurodevelopmental integration of functional brain activity. We show evidence that the cerebellum may play a key role in this process. Human brain development is ongoing from childhood to at least 30 years of age. Functional MRI (fMRI) is key for characterizing changes in brain function that accompany development. However, developmental fMRI studies have relied on reference maps of adult brain organization in the analysis of data from younger subjects. This approach may limit the characterization of functional activity patterns that are particular to children and adolescents. Here we used an emerging fMRI approach called multi-echo fMRI that is not susceptible to such biases when analyzing the variation in functional brain organization over development. We hypothesized an integration of the components of brain activity over development, and found that the number of components decreases exponentially, halving from 8 to 35 years of age. The brain regions most affected underlie executive function and coordination. In summary, we show major changes in the organization and integration of functional networks over development into adulthood, with both methodological and neurobiological implications for future lifespan and disease studies on brain connectivity.
人类功能神经解剖结构的年龄相关性变化尚不清楚。这在一定程度上是由于解释标准 fMRI 数据的局限性。这些限制与不同受试者数据中噪声水平的年龄相关性、以及为发育研究常用的标准成人大脑分割有关。在这里，我们使用一种新兴的 MRI 方法，称为多回波（ME）-fMRI，以描述与年龄相关的功能脑变化。ME-fMRI 在获取血氧水平依赖（BOLD）信号的同时，还量化了磁化率加权横向弛豫时间（T*）信号衰减。这种方法可以可靠地在个体水平上检测到 BOLD 信号成分，而不是仅在组平均水平上检测到。反过来，它支持更稳健地描述个体间功能脑组织的变异性。我们假设静息状态下的 BOLD 成分随年龄的增长而不稳定，并且数量会从青春期到成年期减少。这与当前神经发育分析中关于脑连接的假设相矛盾，即 BOLD 信号成分的数量是一个随机效应。我们对 51 名健康受试者进行了静息状态 ME-fMRI 研究，年龄在 8.3 至 46.2 岁之间，发现 BOLD 成分数量与年龄呈高度显著（ = -0.55， ≪ 0.001）的指数下降。从青春期到中年，BOLD 成分数量减少了一半，在中年稳定下来。驱动这种变化的区域是背外侧前额叶皮层、顶叶皮层和小脑。这些区域的功能网络以小脑为中心。我们得出结论，与神经发育整合功能脑活动的假设一致，BOLD 成分数量随年龄的减少。我们证明了小脑可能在这个过程中发挥关键作用。人类大脑的发育从儿童期持续到至少 30 岁。功能磁共振成像（fMRI）是描述发育过程中伴随的脑功能变化的关键。然而，发育 fMRI 研究在分析年轻受试者的数据时依赖于成人脑组织结构的参考图谱。这种方法可能会限制对儿童和青少年特有的功能活动模式的描述。在这里，我们使用了一种新兴的 fMRI 方法，称为多回波 fMRI，在分析发育过程中功能脑组织结构的变化时，该方法不受这种偏差的影响。我们假设在发育过程中大脑活动成分的整合，并发现数量呈指数下降，从 8 岁到 35 岁减少一半。受影响最大的脑区是执行功能和协调。总之，我们展示了在进入成年期的过程中，功能网络的组织和整合发生了重大变化，这对未来关于大脑连接的寿命和疾病研究具有方法学和神经生物学意义。
