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. 2021 Aug;11(8):e2239.
doi: 10.1002/brb3.2239. Epub 2021 Jun 14.

The degeneration changes of basal forebrain are associated with prospective memory impairment in patients with Wilson's disease

Yutong Wu  1 , Sheng Hu  1   2 , Yi Wang  1 , Ting Dong  3 , Hongli Wu  1 , Yumei Zhang  1 , Qianqian Qu  1 , Anqin Wang  3 , Yinfeng Yang  1 , Chuanfu Li  3 , Hongxing Kan  1
Affiliations

The degeneration changes of basal forebrain are associated with prospective memory impairment in patients with Wilson's disease

Yutong Wu et al. Brain Behav. 2021 Aug.

Abstract

Introduction: Degeneration changes of the basal forebrain (BF) are suggested to play an important role in cognitive impairment and memory loss in patients with Alzheimer's disease and Parkinson's disease. However, little is known about if and how the structure and function of BF are abnormal in Wilson's disease (WD).

Methods: Here, we employed the structural and resting-state functional magnetic resonance imaging (fMRI) data from 19 WD individuals and 24 healthy controls (HC). Voxel-based morphometry (VBM) and functional connectivity analysis were applied to investigate the structural and functional degeneration changes of BF in WD. Moreover, the linear regression analyses were performed in the patient group to depict the correlations between the aberrant gray volume and functional connectivity of the BF and clinical performances, such as the prospective memory (PM) and mini-mental state examination (MMSE).

Results: VBM analysis showed that compared with HC, the volume of overlapping cell groups of BF termed CH1-3 and CH4 was significantly reduced in WD. Additionally, the decreased functional connectivity of the CH4 was distributed in the bilateral temporal-parietal junction (TPJ), right thalamus, orbitofrontal gyrus (ORB), and left middle cingulate cortex (MCC). The performances of the time-based prospective memory (TBPM) and event-based prospective memory (EBPM) were related to reduced functional connectivity between CH4 and right ORB. Besides, the functional connectivity of left TPJ was also significantly correlated with EBPM in WD.

Conclusion: These findings indicated that the degenerative changes of BF may affect PM through the innervation brain function and may help to understand the neural mechanisms underlying cognitive impairment in WD.

Keywords: Wilson's disease; basal forebrain; functional connectivity; functional magnetic resonance imaging; prospective memory; voxel-based morphometry.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
MR image shows BF seed regions and its group differences in volume. (a) The seed regions of BF, including CH1–3 (green) and CH4 (red), were displayed on the axial slice and 3D stereogram in the Montreal Neurological Institute (MNI) space. (b) The volume of CH1–3 and CH4 were significantly reduced in WD patients. The color bar represents p value and 1 – p represents the significant differences between two groups
FIGURE 2
FIGURE 2
Group differences in functional connectivity of CH4. Group‐wise whole‐brain analysis of the FC in contrast with a voxel‐wise p threshold of .001 and cluster‐wise threshold of .01 Abbreviations: L, Left; L_MCC, left middle cingulate cortex; L_TPJ, left temporal‐parietal junction; R, Right; R_ORB, right orbitofrontal gyrus; R_TPJ, right temporal‐parietal junction; R_THA, right thalamus
FIGURE 3
FIGURE 3
The correlations between PM and FC of CH4 in WD patients. (a) Correlation between L_TPJ FC and EBPM. (b) Correlation between R_ORB and EBPM. (c) Correlation between R_ORB FC and TBPM. (d) Correlation between R_TPJ FC and EBPM Abbreviations: EBPM, event‐based expected memory; L_TPJ, left temporal‐parietal junction; R_ORB, right orbitofrontal gyrus; R_TPJ, right temporal‐parietal junction; TBPM, time‐based expected memory
See this image and copyright information in PMC

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