Abstract
Recent evidence suggests that the cerebellum is related to motor and non-motor cognitive functions, and that several coupled cerebro-cerebellar networks exist, including links with the limbic network. Since several limbic structures are affected by Alzheimer pathology, even in the preclinical stages of Alzheimer’s disease (AD), we aimed to investigate the cerebral limbic network activity from the perspective of the cerebellum. Twenty patients with mild cognitive impairment (MCI), 18 patients with AD, and 26 healthy controls (HC) were recruited to acquire Resting-state functional MRI (rs-fMRI). We used seed-based approach to construct the cerebro-cerebellar limbic network. Two-sample t-tests were carried out to explore the differences of the cerebellar limbic network connectivity. The first result, a sub-scale network including the bilateral posterior part of the orbitofrontal cortex (POFC) extending to the anterior insular cortex (AIC) and left inferior parietal lobule (L-IPL), showed greater functional connectivity in MCI than in HC and less functional connectivity in AD than in MCI. The location of this sub-scale network was in accordance with components of the ventral attention network. Second, there was decreased functional connectivity to the right mid-cingulate cortex (MCC) in the AD and MCI patient groups relative to the HC group. As the cerebellum is not compromised by Alzheimer pathology in the prodromal stage of AD, this pattern indicates that the sub-scale ventral attention network may play a pivotal role in functional compensation through the coupled cerebro-cerebellar limbic network in MCI, and the cerebellum may be a key node in the modulation of social cognition.
Highlights
The most prominent feature of Alzheimer’s disease (AD) is the compromise of episodic memory, even in its prodromal stage that is referred to as mild cognitive impairment (MCI)
The number of areas showing negative functional connectivity to the cerebellar limbic network was higher in MCI and AD groups than in the healthy controls (HC)
In a recent report (Delli Pizzi et al, 2019), hippocampal/entorhinal functional connectivity were evaluated in individuals with MCI those who did not convert to AD or show the presence of AD pathological load compared to those who converted to AD or showed presence of AD pathological load, increased functional connectivity to the selected regions, especially the cerebellum, were considered to be the strategy in maintaining the cognitive reserve
Summary
The most prominent feature of Alzheimer’s disease (AD) is the compromise of episodic memory, even in its prodromal stage that is referred to as mild cognitive impairment (MCI). It is natural that the pathogenesis of the impairment of memory became a focus on the research of AD. It is involved in memory function, the limbic system has attracted little attention in AD-related research (Rolls, 2015). Dysfunction of the limbic structures affects emotion regulation, Cerebro-Cerebellar Limbic Network in MCI social interaction, and other behaviors. Understanding the limbic network would be meaningful for deeply probing brain functions, such as memory, and for clarifying the pathogenesis of psychiatric disorders, such as depression (Bennett, 2011), bipolar disorder (Leow et al, 2013), and psychosocial stress (Pruessner et al, 2008). Very few reports have focused on the significance of the limbic network in the evaluation of the biological underpinnings of AD (Trzepacz et al, 2013)
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