Kim Annink

131 The papez circuit and school-age outcome in HIE associated with neurocognitive outcome and episodic memory. In non-cooled infants, the association between hippocampal volumes and episodic memory functioning has been described previously (8,9). The present study confirmed those findings in cooled infants. The MB are also known to be important for episodic memory (26). Recently, Molavi et al. described that 13.2% of the infants with HIE had an abnormal signal intensity on their T2-weighted MRI (10). The strong association between subsequent atrophy of the MB and long-term problems has not been described previously in children with HIE. The association between smaller MB volumes and cognitive and memory impairments has recently been shown in adolescents with a Fontan procedure for a single ventricular heart disease (27). The MB are easy to score without additional software or post-processing and atrophy is significantly associated with neurodevelopmental outcome, hippocampal volumes and FA values, making it an easy indicator for neurodevelopmental outcome. Atrophy of the MB is already visible at three months after birth (10). So, the MB are important to routinely assess in infants with HIE and should be added to the available scoring systems. Besides the hippocampus and MB, the anterior thalamus and fornix are also part of the Papez circuit (11). The thalamus was not associated with outcome in this study, but we were not able to segment the anterior thalamus separately. Also, the fornix could not be reliably segmented with Freesurfer. However, we did find a significant association between normal MB and higher FA values in the fornix and between larger hippocampal volumes and higher FA values in the fornix. Other brain structures should also be taken into account when assessing brain injury in children with HIE during follow-up, since perinatal asphyxia leads to global hypoxic-ischemia of the brain (28). For example, in the TBSS analyses FA values in the anterior corpus callosum were associated with PIQ and visual-spatial long-term memory, and the volume of the corpus callosum was also associated with processing speed and verbal long-term memory (although not significant after correction for multiple comparisons). Furthermore, the amygdala and parahippocampal white matter were associated with hippocampal volumes and might be related to neurodevelopmental outcome in a larger cohort. 6