595 - Amygdala Structure, Connectivity, and Socioemotional Outcomes after Neonatal Hypoxic–Ischaemic Encephalopathy.

Publication Number: 3576.595

Sara Rapuc, University of bristol, Bristol, England, United Kingdom; Arthur Spencer, Department of Radiology, Lausanne University Hospital (CHUV), Lausanne, Vaud, Switzerland; Ela Chakkarapani, University of Bristol, Bristol, England, United Kingdom

Background: Children treated for neonatal hypoxic-ischaemic encephalopathy (HIE) often show reduced brain volumes and socioemotional difficulties later in childhood. The amygdala, central to emotion regulation, may be particularly vulnerable to early injury due to HIE.

Objective: 1. To compare amygdala structure and diffusivity between children treated with therapeutic hypothermia for HIE and controls at 6-8 years.
2. To assess associations between amygdala structural measures and socioemotional outcomes.
3. To explore amygdala functional connectivity differences between HIE cases and controls.

Design/Methods: We included 31 children treated with therapeutic hypothermia for moderate to severe HIE at St Michael's Hospital, Bristol, and 32 age, sex and socioeconomic status-matched controls recruited from local schools (Table 1). Amygdala volumes were derived from structural T1-weighted MRI using FreeSurfer, and mean diffusivity (MD) was assessed using FSL. Socioemotional problems were measured using the Strengths and Difficulties Questionnaire (SDQ) at 6-8 years. Group differences were tested with independent-sample t-tests, and associations between amygdala metrics and SDQ scores were analysed using linear regression models, adjusting for total brain volume (TBV), sex and socioeconomic status. Seed-based resting-state fMRI analyses examined functional connectivity to the amygdala.

Results: Total amygdala volume, corrected for TBV and age at MRI scan, was significantly smaller in the HIE group compared to controls (mean [SD] = 3258 [394] mm³ vs 3543 [317] mm³; t(61)= −3.17, p = .003) (Fig.1). Amygdala MD did not differ between groups (t(51)= 0.29, p = .775).
Children with HIE had higher SDQ scores across all domains than controls. In the HIE group, amygdala volume and MD were associated with externalising (β = −3.51 [95% CI −6.65, −0.37], p = .030) and internalising problems (β = 45.1[95%CI 7.4, 82.8], p = .030) respectively, though the associations were attenuated after adjusting for covariates. No significant associations were observed for total difficulties with amygdala volumes or MD, nor in controls. Functional MRI revealed reduced functional connectivity between the amygdala and the opercular cortex, supramarginal gyrus, superior temporal gyrus, and angular gyrus in HIE cases, persisting after correction for age and sex (Fig.2).

Conclusion(s): Children treated for neonatal HIE show reduced amygdala volume and altered functional connectivity, suggesting persistent structural and connectivity vulnerabilities that may underlie socioemotional difficulties at school age.

Table 1
Baseline characteristics of HIE cases and controls.

Figure 1
Amygdala volumes are reduced in children with HIE treated with therapeutic hypothermia compared with controls.

Figure 2.
Seed-based resting state fMRI analysis showing reduced functional connectivity between the amygdala and the opercular cortex, supramarginal gyrus, superior temporal gyrus and angular gyrus in children treated for HIE with therapeutic hypothermia, corrected for age and sex.