FUNCTIONALLY DISTINCT SUBBUNDLES BETWEEN DOPAMINERGIC MIDBRAIN AND STRIATUM ARE DIFFERENTIALLY AFFECTED IN AD PATIENTS

Abstract

Reward-processing deficits are frequently observed in patients with Alzheimer's disease (AD), but few studies has examined the degeneration of dopaminergic bundles in the reward network of AD patients. By applying the anatomical findings of the connections between the dopaminergic (DA) midbrain and the striatum from primates and healthy subjects, we can investigate whether functionally distinct subbundles between the two regions are differentially affected in AD patients. Setting the DA midbrain as a seed region and the striatum as a target region, we reconstructed the midbrain-striatum bundles (MSB) from the high resolution dMRI data of the Human Connectome Project (HCP) and used the bundles to transfer a ventral-dorsal gradient from the striatum to the DA midbrain. We then obtained a group-average gradient map of the midbrains and divided the DA midbrain into subregions based on gradient values. This allow us to segregate the ventral and dorsal subbundles of the MSB. Using the reconstructed bundles from 10 HCP subjects, we created a high-resolution atlas for the MSB subbundles. Finally, we warped the atlas to lower-resolution ADNI DTI images of 170 NC and 137 AD subjects. For each subject, we computed the fractional anisotropy (FA) and radial diffusivity (RD) of the subbundles for group comparison. AD subjects have significantly lower FA (left:0.377 vs 0.388, p=0.011; right:0.363 vs 0.380, p<0.001) and higher RD (left:0.00061 vs 0.00059, p=0.008; right:0.00070 vs 0.00066, p<0.001) than NC subjects within the ventral subbundle. In the dorsal subbundle, there is no significant difference between AD and NC subjects in FA (left:0.468 vs 0.464, p=1.0; right:0.525 vs 0.533, p=0.22) or RD (left:0.000524 vs 0.000522, p=1.0; right:0.000480 vs 0.000469, p=0.28). All p-values were Bonferroni-corrected. The findings suggested that the subbundles of MSB might be affected differentially in AD. The reward-associated ventral subbundle appeared to degenerate more than the motor-associated dorsal subbundle. This result is consistent with the behavioral observation that AD patients tend to show more reward-processing deficits than motor deficits. Longitudinal analysis is warranted to determine if the differential degeneration observed is a consequence of AD. This work was in part supported by NIH grants RF1AG056573, R01EB022744.