Altered Cerebro-Cerebellar Limbic Network in AD Spectrum: A Resting-State fMRI Study

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.

Differences Changes in Cerebellar Functional Connectivity Between Mild Cognitive Impairment and Alzheimer's Disease: A Seed-Based Approach

“…It is important to note that compared to HC, the connections between cognitive subregions of the cerebellum and the limbic lobe were significantly reduced in AD patients. This result is consistent with a recent study that reported that FC in the cerebellar-limbic network was significantly more vulnerable in AD patients compared to aMCI patients (72).…”

Altered Functional Connectivity of Basal Ganglia in Mild Cognitive Impairment and Alzheimer’s Disease

“…Combining these results, limbic system dysfunction with a disrupted vmPFC circuit [ 9 , 40 ] (including medial OFC and ACC), amygdala-VS (including accumbens, medial caudate), or posterior cerebellum/brain stem/pallidum may be used for explanation. In recent years, there has been a growing number of researchers paying attention to the effect of the limbic system (other than the hippocampus) on AD because of the common neuropsychiatric symptoms, such as emotional and social interaction which are dysregulated by AD [ 41 ]. Structural atrophy [ 6 ] and altered functional connectivity [ 41 ] in the limbic system have been demonstrated in previous studies.…”

Effect of Moxibustion Treatment on Degree Centrality in Patients With Mild Cognitive Impairment: A Resting-State Functional Magnetic Resonance Imaging Study

“…In animal studies, the septocingulate pathway, in which cholinergic neurons of the basal forebrain innervate the cingulate cortex, is critically involved in the working/episodic memory of rats. A study has indicated that patients with MCI had decreased functional connectivity in the MCC ( Qi et al, 2019 ), which related to memory capacity ( Lin et al, 2017 ). These results are consistent with the one of our studies.…”