Development of the corpus callosum and cognition after neonatal encephalopathy

Abstract

Objective: Neonatal imaging studies report corpus callosum abnormalities after neonatal hypoxic-ischaemic encephalopathy (HIE), but corpus callosum development and relation to cognition in childhood are unknown. Using magnetic resonance imaging (MRI), we examined the relationship between corpus callosum size, microstructure and cognitive and motor outcomes at early school-age children cooled for HIE (cases) without cerebral palsy compared to healthy, matched controls. A secondary aim was to examine the impact of HIE-related neonatal brain injury on corpus callosum size, microstructure and growth.

Methods: Participants aged 6-8 years underwent MRI, the Movement Assessment Battery for Children Second Edition and Wechsler Intelligence Scale for Children Fourth Edition. Cross-sectional area, volume, fractional anisotropy and radial diffusivity of the corpus callosum and five subdivisions were measured. Multivariable regression was used to assess associations between total motor score, full-scale IQ (FSIQ) and imaging metrics.

Results: Adjusting for age, sex and intracranial volume, cases (N = 40) compared to controls (N = 39) demonstrated reduced whole corpus callosum area (β = -26.9, 95% confidence interval [CI] = -53.17, -0.58), volume (β = -138.5, 95% CI = -267.54, -9.56), fractional anisotropy and increased radial diffusivity (P < 0.05) within segments II-V. In cases, segment V area (β = 0.18, 95% CI = 0.004, 0.35), volume (β = 0.04, 95% CI = 0.001, 0.079), whole corpus callosum fractional anisotropy (β = 13.8 95% CI = 0.6, 27.1) and radial diffusivity (β = -11.3, 95% CI = -22.22, -0.42) were associated with FSIQ. Growth of the corpus callosum was restricted in cases with a FSIQ ≤85, and volume was reduced in cases with mild neonatal multifocal injury compared to white matter injury alone.

Interpretation: Following neonatal HIE, morphological and microstructural changes in the corpus callosum are associated with reduced cognitive function at early school age.

Figure 1

Recruitment diagram.

Figure 2

Voxelwise comparison of microstructure on the white matter skeleton (green), using tract‐based spatial statistics, revealed areas of reduced FA in cases (A), areas of increased RD in cases (B), and areas in which males exhibit larger case–control differences in FA (C) and RD (D) than females. Significant differences are indicated by areas of red‐yellow for FA images and blue for RD images (P < 0.05). FA, fractional anisotropy; RD, radial diffusivity.

Figure 3

Relationship between CC metrics and neonatal TIS of cases compared to controls. Figures depict CC area and TIS of cases (grey) compared to controls (white) (A); CC volume and TIS of cases compared to controls (B); CC RD and TIS of cases compared to controls (C); CC FA and TIS of cases compared to controls (D). CC, corpus callosum; FA, fractional anisotropy; RD, radial diffusivity; TIS, total injury score.

Figure 4

Relationship between CC metrics and presence of neonatal injury in cases compared to controls as identified through simple linear regression. CC area of cases with no BGT/WM, WM only or BGT/WM injury compared to controls (A); CC volume of cases with no BGT/WM, WM only or BGT/WM injury compared to controls (B); CC RD of cases with no BGT/WM, WM only or BGT/WM injury compared to controls (C); CC FA of cases with no BGT/WM, WM only or BGT/WM injury compared to controls (D). Cases no BGT/WM = case with no BGT/WM injury on neonatal MR brain (BGT score 0). Case WM = cases with any WM lesions on neonatal MR brain (WM score 1–3). Case BGT/WM = cases with any BGT lesions on neonatal MR brain (BGT score 1–2 and WM score 1–3). BGT, basal ganglia and thalami; CC, corpus callosum; FA, fractional anisotropy; RD, radial diffusivity; TIS, total injury score; WM, white matter

Figure 5

Evolution of anterior (A), mid (B) and posterior (C) third and whole (D) CC area from neonatal to early school‐age MRI (n = 36) in cases classified into two groups with an FSIQ ≤85 or >85. Light grey circles represent FSIQ >85, and dark grey circles represent FSIQ ≤85 group. Light and dark grey interrupted lines represent the linear regression lines of the FSIQ >85 and FSIQ ≤85 group. CC, corpus callosum; FSIQ, full‐scale IQ; MRI, magnetic resonance imaging.