Mapping the extra-hippocampal damage in developmental amnesia

Developmental amnesia (DA) is a selective episodic memory disorder associated with hypoxia-induced bilateral hippocampal volume reduction. Despite the systemic impact of hypoxia-ischaemia, the resulting brain damage has been previously reported to be limited to the hippocampus. This thesis explores damage outside of the hippocampus in patients with DA and in those with less severe memory impairment (MI), to provide a full anatomical characterisation of a hypoxia-induced memory disorder. Seventeen patients with DA and fifteen patients with MI participated alongside an equal number of controls. The extent of brain injury was assessed in structural magnetic resonance images using whole-brain (voxel-based morphometry and tract-based spatial statistics) and region-of-interest approaches (automatic and manual measurement of structure volumes). Results showed that in addition to damage to the hippocampus, patients with DA had severe atrophy of the mammillary bodies, mild volume reduction of the thalamus and widespread abnormalities in the white matter. There was only limited evidence of damage in the medial temporal lobe neocortices. By comparison, brain injury in patients with MI was much less extensive. A series of correlations examined the integrity of brain structures in relation to patients’ cognitive outcome. Global abnormalities in the white matter were related to patients’ intelligence, but not to their memory, whereas regional abnormalities in the ventral cingulum predicted performance on tests of verbal recognition. In addition, volumes of a thalamic segment were related to patients’ face recognition ability. Together, these results show that extra-hippocampal abnormalities contribute to the cognitive outcome of patients with DA, independent of the hippocampus, offering support for dual-process models of memory. The findings could lead to new magnetic resonance imaging-based diagnostic measures of developmental amnesia.