Diffusion Tensor Imaging Reveals Microstructural Alterations in Corpus Callosum and Associated Transcallosal Fiber Tracts in Adult Macaques with Neonatal Hippocampal Lesions

摘要

Neonatal hippocampal lesions can result in long-term effects on the morphological and functional integrity of the adult brain. To investigate the effects of neonatal hippocampal lesions on the microstructural integrity of corpus callosum in adulthood, macaque monkeys (n = 5) received neonatal bilateral hippocampal lesion (Neo-Hibo) induced by infusion of ibotenic acid at 1-2 weeks of age and were scanned using diffusion tensor imaging (DTI) at 8-10 years old. Age and gender -matched control animals that had received sham operation (Neo-C, n = 5) at 1-2 weeks of age were scanned for comparison purpose. Corpus callosum was segmented into seven regions that were grouped into anterior corpus callosum (rostrum, genu, rostral body and anterior midbody), posterior corpus callosum (posterior midbody, isthmus and splenium) for data analysis. The associated transcallosal fiber tracts were delineated by using probabilistic tractography and evaluated with TBSS. Significantly increased diffusivity indices (mean, axial and radial diffusivity) were observed in the posterior segments of corpus callosum. Also, significant decreased fractional anisotropy (FA) and increased diffusivity indices were seen in the associated transcallosal fiber tracts proximal to motor, posterior parietal and retrosplenial cortices. Increased mean diffusivity (MD) in posterior midbody negatively correlated with reduction of surface area of corpus callosum in Neo-Hibo monkeys. Also, the magnitude of the memory impairments was significantly correlated with FA in transcallosal fiber tracts across splenium in Neo-Hibo animals. Although no microstructural changes were observed in the anterior segments of corpus callosum, changes in FA values and diffusivity indices were observed in the white matter fibers of the ventromedial prefrontal cortex. This DTI study revealed that neonatal hippocampal lesion resulted in enduring degradation in the adult transcallosal fibers proximal to parietal and retrosplenial cortices, and hemispheric connections through posterior corpus callosum. The findings may provide complementary information for understanding the neural substrate of behavioral and cognitive deficits observed in patients with early insult to the hippocampus.