Development and application of comparative diffusion tensor imaging (DTI) to examine cross-species differences in the hemispheric asymmetry and age-related decline of brain white matter
Errangi, Bhargav Kumar
MetadataShow full item record
A complete scientific understanding of human nature requires delineation of the neurobiological characteristics underlying the unique features of the human mind. This effort can be facilitated by comparing the human brain with the brains of other living primate species. Humans are more susceptible to neurodegenerative diseases than other primate species, including our closest living primate relatives, the chimpanzees. Comparing age-related changes in brain structure between humans and non-human primates could, therefore, potentially shed light on the neurological basis of this human vulnerability. Further, human brains are lateralized with specialized cognitive and behavioral functions. Comparing the magnitude of hemispheric asymmetries in brain structure between humans and non-human primates can probe insights into this human specific capability and learn more about human evolution. Diffusion weighted MRI protocols were developed for different species, taking into account their neuroanatomical differences. For Chimpanzees, a multi-shot DWI sequence was developed and compared with a single-shot DWI sequence to determine which provided a better quality diffusion data free of acquisition related artifacts. Different simulation techniques were used to evaluate the effect of segmentation-related motion artifact (ghosting) on the multi-shot DTI data. Although both protocols generated high-resolution diffusion MRI data with correctable susceptibility-induced distortions, the single-shot protocol enables the acquisition of the high-resolution diffusion MRI data freed of ghosting and with twice the signal-to-noise ratio (SNR), for the same scan duration. The acquired chimpanzee and macaque diffusion data were used to compare the magnitude of microstructural asymmetries and age-related decline of brain white matter with those in humans. Hemispheric asymmetry results show a pattern of strong leftward asymmetry in human DTI indices that differs markedly from the chimpanzee (multi-shot data) and the rhesus macaque patterns involving both rightward and leftward asymmetries. The magnitude of leftward asymmetry increased for chimpanzees scanned with single-shot DTI sequence. Region of interest analyses within the corpus callosum revealed a significant age-related increase in fractional anisotropy (FA) in the genu for chimpanzees (multi-shot data) and no significant change in any region for macaques. Additionally, voxel-wise analysis using Tract Based Spatial Statistics (TBSS) revealed widespread age-related FA increases for chimpanzees (multi-shot data) and weak age-related decreases in FA for macaques across most white matter tracts. Overall, results from these multi-shot data analyses suggest that rhesus monkeys show age-related decreases in white matter integrity that parallel changes found in humans, whereas chimpanzees show age-related increases in white matter integrity. On the contrary, the single-shot data results for chimpanzees revealed no significant relationship between age and the different DTI indices. These noteworthy species differences may help to explain the unique features of the human mind and why humans are more susceptible to neurodegenerative diseases. Furthermore, these studies demonstrate the need for complementary histological studies of white matter microstructure in humans, chimpanzees and macaques to clarify the cellular and molecular basis of these findings.