Center for Mind and Brain, University of California-Davis, 267 Cousteau Place, Davis, CA, 95618, USA.
MIND Institute, University of California-Davis Medical Center, Sacramento, CA, 95817, USA.
Sci Rep. 2020 Sep 29;10(1):16059. doi: 10.1038/s41598-020-73040-0.
Neurobiological basis for cognitive development and psychiatric conditions remains unexplored in children with the FMR1 premutation (PM). Knock-in mouse models of PM revealed defects in embryonic cortical development that may affect cortical folding. Cortical-folding complexity quantified using local gyrification index (LGI) was examined in 61 children (age 8-12 years, 19/14 male/female PM carriers, 15/13 male/female controls). Whole-brain vertex-wise analysis of LGI was performed for group comparisons and correlations with IQ. Individuals with aberrant gyrification in 68 cortical areas were identified using Z-scores of LGI (hyper: Z ≥ 2.58, hypo: Z ≤ - 2.58). Significant group-by-sex-by-age interaction in LGI was detected in right inferior temporal and fusiform cortices, which correlated negatively with CGG repeat length in the PM carriers. Sixteen PM boys (hyper/hypo: 7/9) and 10 PM girls (hyper/hypo: 2/5, 3 both) displayed aberrant LGI in 1-17 regions/person while 2 control boys (hyper/hypo: 0/2) and 2 control girls (hyper/hypo: 1/1) met the same criteria in only 1 region/person. LGI in the precuneus and cingulate cortices correlated positively with IQ scores in PM and control boys while negatively in PM girls and no significant correlation in control girls. These findings reveal aberrant gyrification, which may underlie cognitive performance in children with the PM.
在具有 FMR1 前突变（PM）的儿童中，神经生物学基础对于认知发展和精神状况仍然未知。PM 的敲入小鼠模型显示出胚胎皮质发育缺陷，这可能会影响皮质折叠。使用局部回旋指数（LGI）量化皮质折叠复杂性，并在 61 名儿童（8-12 岁，19/14 名 PM 携带者为男性/女性，15/13 名 PM 携带者为男性/女性）中进行了检查。对 LGI 进行全脑顶点分析，以进行组间比较和与 IQ 的相关性分析。使用 LGI 的 Z 分数（高：Z≥2.58，低：Z≤-2.58）确定 68 个皮质区域中出现异常回旋的个体。在右侧颞下回和梭状回中检测到 LGI 的显著组-性别-年龄相互作用，与 PM 携带者的 CGG 重复长度呈负相关。16 名 PM 男孩（高/低：7/9）和 10 名 PM 女孩（高/低：2/5，3 名均）在 1-17 个区域/人中出现异常 LGI，而 2 名对照男孩（高/低：0/2）和 2 名对照女孩（高/低：1/1）仅在 1 个区域/人中符合相同标准。PM 和对照男孩的楔前叶和扣带回皮质的 LGI 与 IQ 得分呈正相关，而 PM 女孩的 LGI 与 IQ 得分呈负相关，对照女孩则没有显著相关性。这些发现揭示了异常回旋，这可能是 PM 儿童认知表现的基础。
