Intrinsic patterns of coupling between correlation and amplitude of low-frequency fMRI fluctuations are disrupted in degenerative dementia mainly due to functional disconnection.

Daniele Mascali,Michela Fratini,Laura Serra,Federico Giove,Mauro Dinuzzo,Tommaso Gili,Bruno Maraviglia,Marta Moraschi,Marco Bozzali,Emmanuel Andreas Stamatakis

doi:10.1371/journal.pone.0120988

Abstract

Low frequency fluctuations (LFFs) of the BOLD signal are a major discovery in the study of the resting brain with functional magnetic resonance imaging (fMRI). Two fMRI-based measures, functional connectivity (FC), a measure of signal synchronicity, and the amplitude of LFFs (ALFF), a measure of signal periodicity, have been proved to be sensitive to changes induced by several neurological diseases, including degenerative dementia. In spite of the increasing use of these measures, whether and how they are related to each other remains to be elucidated. In this work we used voxel-wise FC and ALFF computed in different frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz; and full-band: 0.01-0.073 Hz), in order to assess their relationship in healthy elderly as well as the relevant changes induced by Alzheimer’s Disease (AD) and Mild Cognitive Impairment (MCI). We found that in healthy elderly subjects FC and ALFF are positively correlated in anterior and posterior cingulate cortex (full-band, slow-4 and slow-5), temporal cortex (full-band and slow-5), and in a set of subcortical regions (full-band and slow-4). These correlation patterns between FC and ALFF were absent in either AD or MCI patients. Notably, the loss of correlation between FC and ALFF in the AD group was primarily due to changes in FC rather than in ALFF. Our results indicate that degenerative dementia is characterized by a loss of global connection rather than by a decrease of fluctuation amplitude.

Highlights

Resting-state functional magnetic resonance imaging has been widely used to investigate the brain function in the absence of a specific task [1]
Patients and controls were matched for age (ANOVA, f = 1.5, p > 0.2) and gender, patients were less educated than controls (t-tests: Alzheimer’s Disease (AD) vs healthy elderly subjects (HC), t = -4.0, p < 0.001; Mild Cognitive Impairment (MCI) vs HC, t = -2.3, p < 0.05)
Our results showed strongly connected regions belonging to the default-mode network (DMN), such as the precuneus/posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC)/ ventral anterior cingulate cortex (ACC), and the inferior temporal/parietal cortex

Summary

Introduction

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used to investigate the brain function in the absence of a specific task [1]. Correlation and Amplitude of Fluctuations in the Resting Brain low frequency (< 0.1 Hz) fluctuations (LFFs) of the blood oxygenation level dependent (BOLD) signal that are synchronized across functionally related and anatomically connected regions. The nature of LFFs is not completely understood, resting-state fMRI has improved the characterization of brain functional architecture. Biswal and colleagues were the first to report highly correlated LFFs in the motor cortex in the absence of task [2]. Thereafter, several studies have consistently shown that specific patterns of synchronized LFFs identify different resting-state networks (RSNs), including, but not limited to visual, auditory, attentive and the so-called default-mode network (DMN) [3, 4]

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