Exploring Altered Cerebral-Cerebellar Network Interactions in Alzheimer's Disease
Poster No:
83
Submission Type:
Abstract Submission
Authors:
Chia-Hsin Chen1, Weiyan Yin1, Yiding Gui1, Xiaoqi Li1, Tengfei Li1, Weili Lin1
Institutions:
1University of North Carolina at Chapel Hill, Chapel Hill, NC
First Author:
Co-Author(s):
Introduction:
Altered brain structures and functional networks in Alzheimer's disease (AD) patients have been widely recognized, particularly in terms of structural atrophy and aberrant functional connectivity (FC) in areas like the hippocampus (Allen et al., 2007; Xue et al., 2019). However, most reported results to date have primarily focused on brain regions within the cerebrum. Recently, emerging evidence has revealed that the cerebellum, traditionally associated with motor control, also plays a critical role in cognitive processes (Zhang et al., 2023; Rudolph et al., 2023; Sokolov et al., 2017). This raises the question of whether altered intra-cerebellar and cerebral-cerebellar functional network interactions are present in AD progression. In this study, we aimed to explore these interactions by leveraging the rich data collected by the Alzheimer's Disease Neuroimaging Initiative (ADNI).
Methods:
A total of 285 participants from ADNI were included in this study, consisting of 95 cognitively normal (CN), 95 mild cognitive impairment (MCI), and 95 AD subjects. Standard rsfMRI preprocessing steps were applied, and the images were registered to the Yeo cerebral 7-network and Buckner cerebellar 7-network atlases. BOLD time series were extracted from predefined regions, excluding time points with framewise displacement (FD) greater than 0.5 mm. Subsequently, intra-cerebral, intra-cerebellar and cerebral-cerebellar functional network interactions were calculated using Pearson correlation, separately. Two-sample t-tests were conducted among the groups, with age, sex, race, and education as covariates. The false discovery rate (FDR) method was used to correct for multiple comparisons.
Results:
Both MCI and AD subjects had significantly fewer years of education than those in the CN group (p < 0.001). In addition, more males were included in the AD group (p = 0.04). The patterns of intra-cerebral, intra-cerebellar and cerebral-cerebellar functional network interactions were shown in Figure 1. While both positive and negative intra-cerebral network interactions were observed, all intra-cerebellar interactions were positive. Interestingly, most of the cerebral-cerebellar network interactions were negative (anticorrelation, >71%) with the MCI exhibiting the highest number of negative interactions (83.7%). Significant alterations of cerebral-cerebellar and intra-cerebellar network interactions were observed among the three groups (Figure 2). Specifically, the anticorrelation between dorsal attention network (DAN) and the cerebellar default mode network (cDMN) was significantly reduced between CN and AD. A similar pattern was also observed for somatomotor network (SMN) and the cerebellar limbic network (cLIM). In contrast, this pattern reversed between the frontoparietal network (FPN) and cLIM (Fig. 2), suggesting opposite interactions between basic (SMN) and higher order (FPN) networks with cLIM as AD progresses. Interestingly, while significant cerebral-cerebellar differences were only observed between CN and AD groups, the intra-cerebellar interactions showed significant reductions between CN and MCI for cSMN-cDAN and cSMN-cFPN, and between CN and MCI as well as AD for cLIM-cDMN pairs, respectively.
Conclusions:
To the best of our knowledge, this is the first study to assess how intra-cerebral, intra-cerebellar and cerebral-cerebellar functional network interactions may be altered during AD progression. Our results revealed distinct cerebral-cerebellar interactions, which were largely anticorrlated. In addition, it appears that the alterations of cerebral-cerebellar interactions are more specific between CN and AD while intra-cerebellar are with CN and MCI, suggesting that their distinct roles as AD progresses. A future prospective study is warranted to further assess the potential roles of the cerebellum in AD progression.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Novel Imaging Acquisition Methods:
BOLD fMRI 2
Keywords:
Cerebellum
Cognition
FUNCTIONAL MRI
1|2Indicates the priority used for review
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2. Xue, J., Guo, H., Gao, Y., Wang, X., Cui, H., Chen, Z., Wang, B., & Xiang, J. (2019). Altered Directed Functional Connectivity of the Hippocampus in Mild Cognitive Impairment and Alzheimer’s Disease: A Resting-State fMRI Study. Frontiers in Aging Neuroscience, 11. https://doi.org/10.3389/fnagi.2019.00326
3. Zhang, P., Duan, L., OU Yu-xiang, Ling, Q., Cao, L., Qian, H., Zhang, J., Wang, J., & Yuan, X. (2023). The cerebellum and cognitive neural networks. Frontiers in Human Neuroscience, 17. https://doi.org/10.3389/fnhum.2023.1197459
4. Rudolph, S., Badura, A., Stefano Lutzu, Salil Saurav Pathak, Thieme, A., Verpeut, J. L., Wagner, M. J., Yang, Y.-M., & Diasynou Fioravante. (2023). Cognitive-Affective Functions of the Cerebellum. The Journal of Neuroscience, 43(45), 7554–7564. https://doi.org/10.1523/jneurosci.1451-23.2023
5. Sokolov, A. A., Miall, R. C., & Ivry, R. B. (2017). The Cerebellum: Adaptive Prediction for Movement and Cognition. Trends in Cognitive Sciences, 21(5), 313–332. https://doi.org/10.1016/j.tics.2017.02.005