Abnormal Amplitude of Low-Frequency Fluctuations of Intrinsic Brain Activity in Alzheimer's Disease

Liu, Xuena; Wang, Siqi; Zhang, Xinqing; Wang, Zhi­qun; Tian, Xiaojie; He, Yong

doi:10.3233/jad-131322

Cited by 107 publications

(102 citation statements)

References 42 publications

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“…Interestingly, however, the cognitive scores did not correlate with ALFF values at all, contradicting previous studies Liu et al, 2014a;Wang et al, 2011), but only with the connectivity values instead. One possible explanation for our results is that PCC ALFF values are altered in mild AD patients, either due to abnormal amyloid deposition, synaptic dysfunction, or metabolic changes, which leads to a disconnection with the parietal and frontal regions (and the latter causes cognitive problems).…”

Section: Discussioncontrasting

confidence: 77%

Differences and the Relationship in Default Mode Network Intrinsic Activity and Functional Connectivity in Mild Alzheimer's Disease and Amnestic Mild Cognitive Impairment

et al. 2014

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There is evidence that the default mode network (DMN) functional connectivity is impaired in Alzheimer's disease (AD) and few studies also reported a decrease in DMN intrinsic activity, measured by the amplitude of low-frequency fluctuations (ALFFs). In this study, we analyzed the relationship between DMN intrinsic activity and functional connectivity, as well as their possible implications on cognition in patients with mild AD and amnestic mild cognitive impairment (aMCI) and healthy controls. In addition, we evaluated the differences both in connectivity and ALFF values between these groups. We recruited 29 controls, 20 aMCI, and 32 mild AD patients. To identify the DMN, functional connectivity was calculated by placing a seed in the posterior cingulate cortex (PCC). Within the DMN mask obtained, we calculated regional average ALFFs. Compared with controls, aMCI patients showed decreased ALFFs in the temporal region; compared with AD, aMCI showed higher values in the PCC but lower in the temporal area. The mild AD group had lower ALFFs in the PCC compared with controls. There was no difference between the connectivity in the aMCI group compared with the other groups, but AD patients showed decreased connectivity in the frontal, parietal, and PCC. Also, PCC ALFFs correlated to functional connectivity in nearly all subregions. Cognitive tests correlated to connectivity values but not to ALFFs. In conclusion, we found that DMN connectivity and ALFFs are correlated in these groups. Decreased PCC ALFFs disrupt the DMN functional organization, leading to cognitive problems in the AD spectrum.

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Section: Discussioncontrasting

confidence: 77%

Differences and the Relationship in Default Mode Network Intrinsic Activity and Functional Connectivity in Mild Alzheimer's Disease and Amnestic Mild Cognitive Impairment

et al. 2014

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“…Such a depression in the amplitude of those frequencies may have not only contributed, in part, to the appearance of the observed shifted peaks but also contributed to the reduced network coherence and synchronicity, allowing for long-distance communication between nodes of a network. In agreement with data presented in previous studies in aging-related pathologies (Han et al, 2011;Liu et al, 2014), these changes and differences observed in the slow-5 band of the resting state are indicative of a vulnerability of the slow-5 oscillations to disruption induced by the progression of normal aging and by the onset of an ischemic stroke.…”

Section: Discussionsupporting

confidence: 92%

Implication of the Slow-5 Oscillations in the Disruption of the Default-Mode Network in Healthy Aging and Stroke

Nair

Mossahebi

et al. 2016

Brain Connectivity

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The processes of normal aging and aging-related pathologies subject the brain to an active re-organization of its brain networks. Among these, the default-mode network (DMN) is consistently implicated with a demonstrated reduction in functional connectivity within the network. However, no clear stipulation on the underlying mechanisms of the de-synchronization has yet been provided. In this study, we examined the spectral distribution of the intrinsic low-frequency oscillations (LFOs) of the DMN sub-networks in populations of young normals, older subjects, and acute and subacute ischemic stroke patients. The DMN sub-networks were derived using a midorder group independent component analysis with 117 eyes-closed resting-state functional magnetic resonance imaging (rs-fMRI) sessions from volunteers in those population groups, isolating three robust components of the DMN among other resting-state networks. The posterior component of the DMN presented noticeable differences. Measures of amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) of the network component demonstrated a decrease in resting-state cortical oscillation power in the elderly (normal and patient), specifically in the slow-5 (0.01-0.027 Hz) range of oscillations. Furthermore, the contribution of the slow-5 oscillations during the resting state was diminished for a greater influence of the slow-4 (0.027-0.073 Hz) oscillations in the subacute stroke group, not only suggesting a vulnerability of the slow-5 oscillations to disruption but also indicating a change in the distribution of the oscillations within the resting-state frequencies. The reduction of network slow-5 fALFF in the posterior DMN component was found to present a potential association with behavioral measures, suggesting a brain-behavior relationship to those oscillations, with this change in behavior potentially resulting from an altered network integrity induced by a weakening of the slow-5 oscillations during the resting state. The repeated identification of those frequencies in the disruption of DMN stresses a critical role of the slow-5 oscillations in network disruption, and it accentuates the importance of managing those oscillations in the health of the DMN.

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“…Thus, the amplitude of LFF (ALFF) may indicate the amplitude of regional spontaneous neuronal activity [27]. Moreover, a number of R-fMRI studies have utilized the ALFF metric to study functional alterations in the hippocampus in patients with AD and/or mild cognitive impairment [21,26,[30][31][32][33][34]. Crosscorrelation coefficient of spontaneous low-frequency (COSLOF) is an index that measures mean connectivity within a brain region.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E ε4 Modulates Cognitive Profiles, Hippocampal Volume, and Resting-State Functional Connectivity in Alzheimer's Disease

Wang¹,

J²,

He³

et al. 2015

JAD

Self Cite

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The apolipoprotein E ε4 (APOE ε4) allele is a well-established genetic risk factor for Alzheimer's disease (AD). Numerous studies have suggested that the modulation of APOE ε4 affects cognition and brain structure and function in healthy populations, particularly in the hippocampus, a key area associated with AD pathology. However, the effect of APOE ε4 allele on cognitive performance, hippocampal structural morphology, and specifically on functional characteristics in patients with AD remains poorly understood. Here, we employed a neuropsychological battery test and multi-modal structural MRI and resting-state functional MRI dataset to systematically investigate cognitive performance, hippocampal structural volume, and functional properties (including local low-frequency oscillating amplitude, intra-regional functional synchrony, and inter-regional functional connectivity) in 16 APOE ε4-carriers and 26 non-carriers at early stages of AD. Compared to non-carriers, APOE ε4-carriers exhibited poorer performance on recognition performance, but performed better on the late item generation of the verbal fluency task (associated with executive function). Structural imaging analysis revealed that APOE ε4-carriers exhibited smaller left hippocampal volumes compared to non-carriers, and the result remains significant after correcting for effects of brain size. Functional imaging analysis revealed that APOE ε4-carriers exhibited decreased amplitude of low-frequency fluctuations in the left hippocampus, non-significant changes in intra-regional synchronization within the hippocampus and decreased hippocampal functional connectivity predominantly in components of the default-mode network including the medial frontal and parietal cortices and the lateral temporal cortical regions. Taken together, our results showed APOE genotypic effects on the cognitive profile and hippocampal structural and functional characteristics in patients at early stages of AD, thus providing empirical evidence for the modulation of the APOE genotype on disease phenotype.

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Abnormal Amplitude of Low-Frequency Fluctuations of Intrinsic Brain Activity in Alzheimer's Disease

Cited by 107 publications

References 42 publications

Differences and the Relationship in Default Mode Network Intrinsic Activity and Functional Connectivity in Mild Alzheimer's Disease and Amnestic Mild Cognitive Impairment

Differences and the Relationship in Default Mode Network Intrinsic Activity and Functional Connectivity in Mild Alzheimer's Disease and Amnestic Mild Cognitive Impairment

Implication of the Slow-5 Oscillations in the Disruption of the Default-Mode Network in Healthy Aging and Stroke

Apolipoprotein E ε4 Modulates Cognitive Profiles, Hippocampal Volume, and Resting-State Functional Connectivity in Alzheimer's Disease

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