Altered microstructural pattern of the cortex and basal forebrain cholinergic system in wilson's disease: an automated fiber quantification tractography study.

Abstract

Basal forebrain (BF) cholinergic projection neurons form a highly extensive input to the cortex. Failure of BF cholinergic circuits is responsible for the cognitive impairment associated with Wilson's disease (WD), but whether and how the microstructural changes in fiber projections between the BF and cerebral cortex influence prospective memory (PM) remain poorly understood. We collected diffusion tensor imaging (DTI) data from 21 neurological WD individuals and 26 healthy controls (HCs). The experiment reconstructed the probabilistic streamlined tractography of 18 white matter tracts using an automated fiber quantification (AFQ) toolkit. Tract properties (FA, MD, RD, and AD) were computed for 100 points along each tract for each participant, and the differences between the groups were examined. Subsequently, correlation analysis was performed to evaluate whether abnormal microstructural white matter integrity measures correlate with PM performance. Additional investigations used a tract-based spatial statistics (TBSS) approach to identify regions with altered white matter structure between groups and verify the reliability of the AFQ results. The highest nonoverlapping DTI-related differences were detected in the anterior thalamic radiation (ATR), corticospinal tract (CST), corpus callosum, association fibers, and limbic system fibers. Additionally, PM parameters of the patient group were highly correlated with white matter microstructure changes in the inferior longitudinal fasciculus. Our study highlights that the performance of projections between cholinergic input and output areas-the cerebral cortex and BF-may serve as neural biomarkers of PM and disease prognosis.