Amplitude Of Low-frequency Fluctuation Maps Research Articles

Neurovascular coupling dysfunction in high myopia patients: Evidence from a multi-modal magnetic resonance imaging analysis

Background and purposeTo investigate neurovascular coupling dysfunction in high myopia (HM) patients. Materials and methodsA total of 37 HM patients and 36 healthy controls were included in this study. Degree centrality (DC), regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF) maps were employed to represent neuronal activity. Cerebral blood perfusion was characterized by cerebral blood flow (CBF). The correlation coefficient was calculated to reflect the relationship between neuronal activity and cerebral blood perfusion. Pearson partial correlation analysis was utilized to evaluate the association between HM dysfunction and clinical indicators. ResultsHM patients exhibited significant alterations in neurovascular coupling across 37 brain regions compared to healthy controls. The brain regions with marked changes varied among the four neurovascular coupling patterns, including the middle frontal gyrus, superior occipital gyrus, middle occipital gyrus, and fusiform gyrus. Additionally, the superior frontal gyrus orbital part, medial superior frontal gyrus, inferior occipital gyrus, and dorsolateral superior frontal gyrus displayed significant changes in three coupling patterns. In HM patients, the ReHo-CBF changes in the inferior frontal gyrus orbital part were positively correlated with best-corrected visual acuity (BCVA) and refractive diopter changes. Similarly, the ALFF-CBF changes in the inferior frontal gyrus orbital part showed a positive correlation with refractive diopter changes. ReHo-CBF and ALFF-CBF alterations in the paracentral lobule were positively correlated with BCVA and refractive diopter changes. ConclusionOur findings underscore the abnormal alterations in neurovascular coupling across multiple brain regions in HM patients. These results suggest that neurovascular dysfunction in HM patients may be associated with an aberrant visual regulation mechanism.

The relationship between abnormal cortical activity in the anterior cingulate gyrus and cognitive dysfunction in patients with end- stage renal disease: a fMRI study on the amplitude of low- frequency fluctuations.

End-stage renal disease (ESRD) patients often have cognitive dysfunction. The abnormal changes in the brains of ESRD patients are difficult to detect with routine imaging examination. Cognitive performance scales are also not an ideal tool because assessments using these scales can be subjective and might be difficult to administer in some ESRD patients. Functional magnetic resonance has the advantages of non-radiation, multidirectional imaging, good repeatability. Using resting-state functional magnetic resonance imaging (rs-fMRI) and an amplitude of low-frequency fluctuation (ALFF) algorithm, this study characterized spontaneous brain activity and explored its relationship with cognitive function in ESRD patients. The aim of this study was to provide objective functional imaging evidence to reveal the pathophysiological mechanism of cognitive dysfunction in ESRD patients. This study recruited 35 ESRD patients and 25 healthy controls (HC) who were matched to the ESRD group by age, sex, and years of education. All study subjects were examined by Montreal Cognitive Assessment (MoCA) and rs-fMRI. Data Processing & Analysis of Brain Imaging (DPABI) V4.3 software was used to preprocess the data to obtain ALFF maps. The ALFF value of the cingulate gyrus was compared between the ESRD and HC groups. Subsequently, the correlation between the ALFF value of the cingulate gyrus and the MoCA score was analyzed in ESRD patients. Compared with the HC group, the ESRD group had a significantly lower MoCA score (P<0.05). The ALFF values of the anterior and middle cingulate gyri were significantly lower in the ESRD patients (Gaussian random field (GRF) corrected, voxel-level significance: P<0.001, cluster-level significance: P<0.05). No increased ALFF was observed in any brain regions. The ALFF values of the bilateral anterior cingulate gyri were positively correlated with the MoCA scores (r=0.768, 0.625, GRF corrected, voxel-level significance: P<0.01, cluster-level significance: P<0.05). Patients with ESRD showed impaired spontaneous brain activity in the bilateral anterior and middle cingulate gyri, suggesting that ALFF of the anterior cingulate gyrus may be an imaging indicator of cognitive dysfunction in ESRD patients.

Functional Magnetic Resonance Imaging Activation Optimization in the Setting of Brain Tumor-Induced Neurovascular Uncoupling Using Resting-State Blood Oxygen Level-Dependent Amplitude of Low Frequency Fluctuations.

The goal of this study was to demonstrate that a novel resting state BOLD ALFF (amplitude of low frequency fluctuations)-based correction method can substantially enhance the detectability of motor task activation in the presence of tumor-induced neurovascular uncoupling (NVU). Twelve de novo brain tumor patients who underwent comprehensive clinical BOLD fMRI exams including task fMRI and resting state fMRI (rsfMRI) were evaluated. Each patient displayed decreased/absent task fMRI activation in the ipsilesional primary motor cortex in the absence of corresponding motor deficit or suboptimal task performance, consistent with NVU. Z-score maps for the motor tasks were obtained from general linear model (GLM) analysis (reflecting motor activation vs. rest). ALFF maps were calculated from rsfMRI data. Precentral and postcentral gyri in contralesional (CL) and ipsilesional (IL) hemispheres were parcellated using an Automated Anatomical Labeling (AAL) template for each patient. A novel ALFF-based correction method was used to identify the NVU affected voxels in the ipsilesional primary motor cortex (PMC), and a correction factor was applied to normalize the baseline Z-scores for these voxels. In all cases, substantially greater activation was seen on post-ALFF correction motor activation maps within the ipsilesional precentral gyri than in the pre-ALFF correction activation maps. We have demonstrated the feasibility of a new resting state ALFF-based technique for effective correction of brain tumor-related NVU in the primary motor cortex.

Investigating the predictive value of different resting-state functional MRI parameters in obsessive-compulsive disorder

Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies of obsessive-compulsive disorder (OCD) have facilitated our understanding of OCD pathophysiology based on its intrinsic activity. However, whether the group difference derived from univariate analysis could be useful for informing the diagnosis of individual OCD patients remains unclear. We aimed to apply multivariate pattern analysis of different rs-fMRI parameters to distinguish drug-naive patients with OCD from healthy control subjects (HCS). Fifty-four drug-naive OCD patients and 54 well-matched HCS were recruited. Four different rs-fMRI parameter maps, including the amplitude of low-frequency fluctuations (ALFF), fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo) and functional connectivity strength (FCS), were calculated. Training of a support vector machine (SVM) classifier using rs-fMRI maps produced voxelwise discrimination maps. Overall, the classification accuracies were acceptable for the four rs-fMRI parameters. Excellent performance was achieved when ALFF maps were employed (accuracy, 95.37%, p < 0.01), good performance was achieved by using ReHo maps, weaker performance was achieved by using fALFF maps, and fair performance was achieved by using FCS maps. The brain regions showing the greatest discriminative power included the prefrontal cortex, anterior cingulate cortex, precentral gyrus, and occipital lobes. The application of SVM to rs-fMRI features may provide potential power for OCD classification.

Changes in resting-state functional brain activity are associated with waning cognitive functions in HIV-infected children.

Delayed brain development in perinatally HIV-infected children may affect the functional brain activity and subsequently cognitive function. The current study evaluated the functional brain activity in HIV-infected children by quantifying the amplitude of low frequency fluctuations (ALFF) and functional connectivity (FC). Additionally, correlation of ALFF and FC with cognitive measures was performed. Twenty-six HIV-infected children and 20 control children underwent neuropsychological (NP) assessment and resting-state functional magnetic resonance imaging (rs-fMRI). ALFF and FC maps were generated and group differences were analyzed using two-sample t-test. Furthermore, ALFF and FC showing significant group differences were correlated with NP scores using Pearson's correlation. Significantly lower ALFF in the left middle temporal gyrus, precentral and post central gyrus was observed in HIV-infected children compared to controls. FC was significantly reduced in the right inferior parietal, vermis, middle temporal and left postcentral regions, and significantly increased in the right precuneus, superior parietal and left middle frontal regions in HIV-infected children as compared to control. HIV-infected children showed significantly lower NP scores in various domains including closure, exclusion, memory, verbal meaning, quantity and hidden figure than controls. These waning cognitive functions were significantly associated with changes in ALFF and FC in HIV-infected children. The findings suggest that abnormal ALFF and FC may responsible for cognitive deficits in HIV-infected children. ALFF and FC in association with cognitive evaluation may provide a clinical biomarker to evaluate functional brain activity and to plan neurocognitive intervention in HIV-infected children undergoing standard treatment.

Atypical developmental trajectory of local spontaneous brain activity in autism spectrum disorder

Autism spectrum disorder (ASD) is marked by atypical trajectory of brain maturation, yet the developmental abnormalities in brain function remain unclear. The current study examined the effect of age on amplitude of low-frequency fluctuations (ALFF) in ASD and typical controls (TC) using a cross-sectional design. We classified all the participants into three age cohorts: child (<11 years, 18ASD/20TC), adolescent (11–18 years, 28ASD/26TC) and adult (≥18 years, 18ASD/18TC). Two-way analysis of variance (ANOVA) was performed to ascertain main effects and interaction effects on whole brain ALFF maps. Results exhibited significant main effect of diagnosis in ASD with decreased ALFF in the right precuneus and left middle occipital gyrus during all developmental stages. Significant diagnosis-by-age interaction was observed in the medial prefrontal cortex (mPFC) with ALFF lowered in autistic children but highered in autistic adolescents and adults. Specifically, remarkable quadratic change of ALFF with increasing age in mPFC presented in TC group was absent in ASD. Additionally, abnormal ALFF values in diagnosis-related brain regions predicted the social deficits in ASD. Our findings indicated aberrant developmental patterns of spontaneous brain activity associated with social deficits in ASD and highlight the crucial role of the default mode network in the development of disease.

APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults: A STROBE Article.

To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging.Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests.There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P < 0.05, Alphasim corrected). No differences of DMN FCs were found between the ε2/ε3 and ε3/ε3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P < 0.05).APOE ε4 carriers exhibited significantly increased DMN FCs when compared with ε3 and ε2 carriers. The ε4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect.

Neural activity changes in unaffected children of patients with schizophrenia: A resting-state fMRI study

Previous neuroimaging studies have suggested that individuals at risk for schizophrenia exhibit structural and functional brain abnormalities. However, few studies focus on resting state baseline activity in individuals with genetic high-risk for schizophrenia (HR). We examined cerebral spontaneous neural activity in HR by measuring the amplitude of low frequency fluctuations (ALFF) in the blood oxygen level-dependent (BOLD) functional magnetic resonance signal during resting state. Using a 3T MRI scanner, 28 non-psychotic young adult participants with at least one parent with schizophrenia and 44 matched unrelated healthy comparison subjects (HC) were scanned during the resting-state. The ALFF of the BOLD signal for each participant was calculated, and these values were then compared between-groups using voxel-based analysis of the ALFF maps. The HR group showed significantly increased ALFF compared to the HC group in the striatum, including the left caudate nucleus extending to the putamen and the right caudate nucleus. There was also increased ALFF in HR relative to controls in the left medial temporal region including hippocampus, parahippocampal gyrus and the fusiform gyrus, as well as regions including the left lateral thalamus, bilateral ventral and dorsal anterior cingulate cortex, bilateral calcarine sulcus and precuneus. There was significantly decreased ALFF in the HR group relative to controls in the left inferior parietal lobule/postcentral gyrus. Our findings suggest that altered intrinsic neuronal activity in cortico-striato-thalamic networks may represent genetic vulnerability for the development of schizophrenia.

Altered Amplitude of Low-frequency Fluctuations in Early and Late Mild Cognitive Impairment and Alzheimer's Disease

Previous studies have shown that the strength of the low frequency fluctuation in the medial-line brain areas are abnormally reduced in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. The purpose of this study was to explore the functional brain changes in early MCI (EMCI) and late MCI (LMCI) patients by measuring the amplitude of the blood oxygenation level dependent (BOLD) functional MRI (fMRI) signals at rest. 35 elderly normal controls (NC), 24 EMCI, 29 LMCI, and 14 AD patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI2) were included in this study. Resting state fMRI and 3D structural MRI data were acquired. The spatial patterns of spontaneous brain activity were measured by examining the amplitude of low-frequency fluctuations (ALFF) of BOLD signal during rest. A one-way analysis of variance (ANOVA) was then performed on ALFF maps, with age, sex and regional atrophy as covariates. There were widespread ALFF differences among the four groups. As compared with controls, AD, LMCI and EMCI patients showed decreased ALFF mainly in the posterior cingulate cortex, precuneus, right lingual gyrus and thalamus (with a linear trend: NC>EMCI>LMCI>AD), while there was increased activity in the right parahippocampal gyrus (with a linear trend: NC<EMCI<LMCI<AD). Additionally, we also showed that many regions with ALFF changes had significant correlations with the cognitive performance as measured by mini-mental state examination scores (MMSE) and the emotion states as measured by Geriatric Depression Scale (GD scale) for EMCI, LMCI and AD patients, but not for controls. Our results indicated that the significantly altered ALFF activities can be detected at EMCI stage, independent of age, sex and regional atrophy. The present study thus suggests ALFF abnormalities as a potential biomarker for the early diagnosis of AD and further provides insights into biological mechanisms of the diseases.

Amplitude of low-frequency fluctuations in bipolar disorder: A resting state fMRI study

ObjectivesThe spontaneous low frequency fluctuations (LFF) of blood oxygenation level-dependent (BOLD) signal in resting state have been identified as a biological measure of baseline spontaneous activity in the brain. Increasingly, studies of spontaneous resting state functional connectivity have demonstrated neural network abnormalities in bipolar disorder (BD). This study used the amplitude of low frequency fluctuations (ALFF) to explore the regional functional changes in BD during resting state. MethodsTwenty-nine BD participants and 29 matched healthy controls (HC) were recruited to undergo resting-state functional magnetic resonance imaging scan on a 3.0T magnetic resonance imaging system. The ALFF of BOLD signal in gray matter for each participant was calculated, and then was compared between BD and HC using ALFF maps. ResultsCompared to the HC group, the BD group showed increased ALFF in ventral prefrontal cortex, dorsal lateral prefrontal cortex, frontal eye field, insula, and putamen with extension into the ventral striatum, as well as decreased ALFF in the lingual gyrus (p<0.05, corrected). LimitationsAlthough we observed differences in ALFF between BD and HC, we cannot conclusively state that these differences are caused by the pathophysiology of BD since most of BD participants were being treated with medications at the time of scanning. ConclusionsOur results revealed altered regional brain activity in BD during resting state. The affected regions have been associated with BD pathophysiology. This suggests that methods using ALFF method may potentially be useful in further studies of this disorder.

The Influence of the Amplitude of Low-Frequency Fluctuations on Resting-State Functional Connectivity

Studies of brain functional connectivity have provided a better understanding of organization and integration of large-scale brain networks. Functional connectivity using resting-state functional magnetic resonance imaging (fMRI) is typically based upon the correlations of the low-frequency fluctuation of fMRI signals. Reproducible spatial maps in the brain have also been observed using the amplitude of low-frequency fluctuations (ALFF) in resting-state. However, little is known about the influence of the ALFF on the functional connectivity measures. In the present study, we analyzed resting-state fMRI data on 79 healthy old individuals. Spatial independent component analysis and regions of interest (ROIs) based connectivity analysis were performed to obtain measures of functional connectivity. ALFF maps were also calculated. First, voxel-matched inter-subject correlations were computed between back-reconstructed IC and ALFF maps. For all the resting-state networks, there was a consistent correlation between ALFF variability and network strengths (within regions that had high IC strengths). Next, inter-subject variance of correlations across 160 functionally defined ROIs were correlated with the corresponding ALFF variance. The connectivity of several ROIs to other regions were more likely to correlate with its own regional ALFF. These regions were mainly located in the anterior cingulate cortex, medial prefrontal cortex, precuneus, insula, basal ganglia, and thalamus. These associations may suggest a functional significance of functional connectivity modulations. Alternatively, the fluctuation amplitudes may arise from physiological noises, and therefore, need to be controlled when studying resting-state functional connectivity.

MRI assessment of amplitude of low-frequency fluctuation in rat brains with acute cerebral ischemic stroke

To investigate fluctuations in the amplitude of low-frequency blood oxygenation level-dependent (BOLD) fMRI during acute brain ischemia, and to evaluate the use of amplitude of low-frequency fluctuations (ALFFs) in resting state fMRI for assessing super-acute focal cerebral ischemic stroke. A super-acute stroke model with middle cerebral artery occlusion (MCAO) in the rat was employed. Spontaneous fluctuations were recorded using a series of gradient echo-planar imaging (EPI) images before and 30min, 60min, 2h, 6h, 12h, and 24h after MCAO. After preprocessing, serial fMRI data were obtained by fast Fourier transformation to calculate the ALFFs. Statistical parametric mapping software was used for the statistical analysis of ALFFs. T2-weighted images and diffusion weighted images (DWI) were also performed to detect the ischemic lesion. The signal intensities of abnormal ALFFs increased and migrated from the core of the ischemic lesion areas to the edge of lesion following MCAO. The dynamic changes in the ALFF maps demonstrated that the sizes of the ALFF regions exceeded beyond the borderline of the DWI lesions during the super-acute ischemic stroke stage. There was a significant difference in the ALFFs maps between the ischemic stroke group and the control group (P<0.005; cluster size>10 voxels), which mainly occurred in the periphery of the ischemic region in the cortex. These data suggest that ALFF maps provide hemodynamic BOLD information on neural activity, and have potential for predicting survival and prognosis of acute ischemic brain tissues.