Frequency-dependent alterations in functional connectivity in patients with Alzheimer's Disease spectrum disorders

Abstract

Background: In the spectrum of Alzheimer's Disease (AD) and related disorders, the resting-state functional magnetic resonance imaging (rs-fMRI) signals within the cerebral cortex may exhibit distinct characteristics across various frequency ranges. Nevertheless, this hypothesis has not yet been substantiated within the broader context of whole-brain functional connectivity. This study aims to explore potential modifications in degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) among individuals with amnestic mild cognitive impairment (aMCI) and AD, while assessing whether these alterations differ across distinct frequency bands.

Methods: This investigation encompassed a total of 53 AD patients, 40 aMCI patients, and 40 healthy controls (HCs). DC and VMHC values were computed within three distinct frequency bands: classical (0.01-0.08 Hz), slow-4 (0.027-0.073 Hz), and slow-5 (0.01-0.027 Hz) for the three respective groups. To discern differences among these groups, ANOVA and subsequent post hoc two-sample t-tests were employed. Cognitive function assessment utilized the mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA). Pearson correlation analysis was applied to investigate the associations between MMSE and MoCA scores with DC and VMHC.

Results: Significant variations in degree centrality (DC) were observed among different groups across diverse frequency bands. The most notable differences were identified in the bilateral caudate nucleus (CN), bilateral medial superior frontal gyrus (mSFG), bilateral Lobule VIII of the cerebellar hemisphere (Lobule VIII), left precuneus (PCu), right Lobule VI of the cerebellar hemisphere (Lobule VI), and right Lobule IV and V of the cerebellar hemisphere (Lobule IV, V). Likewise, disparities in voxel-mirrored homotopic connectivity (VMHC) among groups were predominantly localized to the posterior cingulate gyrus (PCG) and Crus II of the cerebellar hemisphere (Crus II). Across the three frequency bands, the brain regions exhibiting significant differences in various parameters were most abundant in the slow-5 frequency band.

Conclusion: This study enhances our understanding of the pathological and physiological mechanisms associated with AD continuum. Moreover, it underscores the importance of researchers considering various frequency bands in their investigations of brain function.

Keywords: Alzheimer’s disease; amnestic mild cognitive impairment; degree centrality; resting-state functional magnetic resonance imaging; slow-5 frequency band; voxel-mirrored homotopic connectivity.

Figure 1

Significant differences in DC among NC, aMCI, and AD in different frequency bands: (A) classical frequency band; (B) slow-5 frequency band; (C) slow-4 frequency band.

Figure 2

Post hoc comparisons of analysis of variance. The connection between two bars represents significant between-group differences (* indicates a significant level of p < 0.05, ** denotes a significant level of p < 0.01, and *** indicates a significant level of p < 0.001, Bonferroni correction). AD, Alzheimer’s disease; aMCI, amnestic mild cognitive impairment; NC, normal controls; Lobule VI, Lobule VI of the cerebellar hemisphere; CN, caudate nucleus; mSFG, medial superior frontal gyrus; Lobule VIII, Lobule VIII of the cerebellar hemisphere; Lobule IV, V, Lobule IV, V of the cerebellar hemisphere; mSFG, medial superior frontal gyrus; PCu, precuneus.

Figure 3

Significant differences of VMHC among NC, aMCI, and AD in different frequency bands: (A) classical frequency band; (B) slow-5 frequency band; (C) slow-4 frequency band.

Figure 4

Post hoc comparisons of analysis of variance. The connection between two bars represents significant between-group differences (* indicates a significant level of p < 0.05, ** denotes a significant level of p < 0.01, and *** indicates a significant level of p < 0.001, Bonferroni correction). AD, Alzheimer’s disease; aMCI, amnestic mild cognitive impairment; NC, normal controls; PCG, posterior cingulate gyrus; Crus II, Crus II of the cerebellar hemisphere.

Figure 5

Correlation between MMSE and MoCA scales and DC and VMHC values in patients. The y-axis represents MMSE (Mini-Mental State Examination) or MoCA (Montreal Cognitive Assessment) scores, while the x-axis represents DC or VMHC values.