Ullman Henrik, Spencer-Smith Megan, Thompson Deanne K, Doyle Lex W, Inder Terrie E, Anderson Peter J, Klingberg Torkel
1 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
1 Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden 2 School of Psychological Sciences, Monash University, Melbourne, Australia 3 Clinical Sciences, Murdoch Childrens Research Institute, Melbourne, Australia.
Brain. 2015 Nov;138(Pt 11):3251-62. doi: 10.1093/brain/awv244. Epub 2015 Sep 1.
School-age children born preterm are particularly at risk for low mathematical achievement, associated with reduced working memory and number skills. Early identification of preterm children at risk for future impairments using brain markers might assist in referral for early intervention. This study aimed to examine the use of neonatal magnetic resonance imaging measures derived from automated methods (Jacobian maps from deformation-based morphometry; fractional anisotropy maps from diffusion tensor images) to predict skills important for mathematical achievement (working memory, early mathematical skills) at 5 and 7 years in a cohort of preterm children using both univariable (general linear model) and multivariable models (support vector regression). Participants were preterm children born <30 weeks' gestational age and healthy control children born ≥37 weeks' gestational age at the Royal Women's Hospital in Melbourne, Australia between July 2001 and December 2003 and recruited into a prospective longitudinal cohort study. At term-equivalent age ( ±2 weeks) 224 preterm and 46 control infants were recruited for magnetic resonance imaging. Working memory and early mathematics skills were assessed at 5 years (n = 195 preterm; n = 40 controls) and 7 years (n = 197 preterm; n = 43 controls). In the preterm group, results identified localized regions around the insula and putamen in the neonatal Jacobian map that were positively associated with early mathematics at 5 and 7 years (both P < 0.05), even after covarying for important perinatal clinical factors using general linear model but not support vector regression. The neonatal Jacobian map showed the same trend for association with working memory at 7 years (models ranging from P = 0.07 to P = 0.05). Neonatal fractional anisotropy was positively associated with working memory and early mathematics at 5 years (both P < 0.001) even after covarying for clinical factors using support vector regression but not general linear model. These significant relationships were not observed in the control group. In summary, we identified, in the preterm brain, regions around the insula and putamen using neonatal deformation-based morphometry, and brain microstructural organization using neonatal diffusion tensor imaging, associated with skills important for childhood mathematical achievement. Results contribute to the growing evidence for the clinical utility of neonatal magnetic resonance imaging for early identification of preterm infants at risk for childhood cognitive and academic impairment.
早产的学龄儿童尤其面临数学成绩低的风险,这与工作记忆和数字技能下降有关。使用脑标志物早期识别有未来损伤风险的早产儿童可能有助于转介进行早期干预。本研究旨在检验使用自动方法得出的新生儿磁共振成像测量指标(基于变形形态测量的雅可比映射;扩散张量图像的分数各向异性映射),通过单变量(一般线性模型)和多变量模型(支持向量回归)来预测一组早产儿童在5岁和7岁时对数学成绩重要的技能(工作记忆、早期数学技能)。参与者为2001年7月至2003年12月期间在澳大利亚墨尔本皇家妇女医院出生孕周小于30周的早产儿童和出生孕周大于等于37周的健康对照儿童,他们被纳入一项前瞻性纵向队列研究。在足月等效年龄(±2周)时,招募了224名早产婴儿和46名对照婴儿进行磁共振成像。在5岁(早产组n = 195;对照组n = 40)和7岁(早产组n = 197;对照组n = 43)时评估工作记忆和早期数学技能。在早产组中,结果确定了新生儿雅可比映射中岛叶和壳核周围的局部区域,这些区域与5岁和7岁时的早期数学呈正相关(均P < 0.05),即使在使用一般线性模型对重要的围产期临床因素进行协变量调整后也是如此,但支持向量回归模型未显示这种相关性。新生儿雅可比映射在7岁时与工作记忆的关联也呈现相同趋势(模型P值范围从0.07到0.05)。即使在使用支持向量回归对临床因素进行协变量调整后,新生儿分数各向异性在5岁时与工作记忆和早期数学呈正相关(均P < 0.001),但一般线性模型未显示这种相关性。在对照组中未观察到这些显著关系。总之,我们在早产脑中,利用基于新生儿变形的形态测量确定了岛叶和壳核周围的区域,并利用新生儿扩散张量成像确定了与儿童数学成绩重要技能相关的脑微结构组织。研究结果为新生儿磁共振成像在早期识别有儿童认知和学业损伤风险的早产婴儿方面的临床应用提供了越来越多的证据。