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Characterizing dynamic amplitude of low-frequency fluctuation and its relationship with dynamic functional connectivity: An application to schizophrenia.

ABSTRACT: The human brain is a highly dynamic system with non-stationary neural activity and rapidly-changing neural interaction. Resting-state dynamic functional connectivity (dFC) has been widely studied during recent years, and the emerging aberrant dFC patterns have been identified as important features of many mental disorders such as schizophrenia (SZ). However, only focusing on the time-varying patterns in FC is not enough, since the local neural activity itself (in contrast to the inter-connectivity) is also found to be highly fluctuating from research using high-temporal-resolution imaging techniques. Exploring the time-varying patterns in brain activity and their relationships with time-varying brain connectivity is important for advancing our understanding of the co-evolutionary property of brain network and the underlying mechanism of brain dynamics. In this study, we introduced a framework for characterizing time-varying brain activity and exploring its associations with time-varying brain connectivity, and applied this framework to a resting-state fMRI dataset including 151 SZ patients and 163 age- and gender matched healthy controls (HCs). In this framework, 48 brain regions were first identified as intrinsic connectivity networks (ICNs) using group independent component analysis (GICA). A sliding window approach was then adopted for the estimation of dynamic amplitude of low-frequency fluctuation (dALFF) and dFC, which were used to measure time-varying brain activity and time-varying brain connectivity respectively. The dALFF was further clustered into six reoccurring states by the k-means clustering method and the group difference in occurrences of dALFF states was explored. Lastly, correlation coefficients between dALFF and dFC were calculated and the group difference in these dALFF-dFC correlations was explored. Our results suggested that 1) ALFF of brain regions was highly fluctuating during the resting-state and such dynamic patterns are altered in SZ, 2) dALFF and dFC were correlated in time and their correlations are altered in SZ. The overall results support and expand prior work on abnormalities of brain activity, static FC (sFC) and dFC in SZ, and provide new evidence on aberrant time-varying brain activity and its associations with brain connectivity in SZ, which might underscore the disrupted brain cognitive functions in this mental disorder.

SUBMITTER: Fu Z

PROVIDER: S-EPMC5860934 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Characterizing dynamic amplitude of low-frequency fluctuation and its relationship with dynamic functional connectivity: An application to schizophrenia.

Fu Zening Z Tu Yiheng Y Di Xin X Du Yuhui Y Pearlson G D GD Turner J A JA Biswal Bharat B BB Zhang Zhiguo Z Calhoun V D VD

NeuroImage 20170920 Pt B

The human brain is a highly dynamic system with non-stationary neural activity and rapidly-changing neural interaction. Resting-state dynamic functional connectivity (dFC) has been widely studied during recent years, and the emerging aberrant dFC patterns have been identified as important features of many mental disorders such as schizophrenia (SZ). However, only focusing on the time-varying patterns in FC is not enough, since the local neural activity itself (in contrast to the inter-connectivi ...[more]

PMID: 28939432

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Project description:Objective: A limited number of studies have previously reported on the regional activity [amplitude of low-frequency fluctuation (ALFF)] and functional integration [functional connectivity (FC)] of the whole brain in deficit schizophrenia (DS). The present study investigates the resting-state characteristics of the fractional ALFF (fALFF) and the FC in both DS and non-deficit schizophrenia (NDS) patients, and further explores their correlations with neurocognitive features. Methods: Demographic, resting-state functional magnetic resonance imaging (MRI), and neurocognitive data were collected from 33 DS and 41 NDS male patients, as well as in 40 male healthy controls (HCs). The voxel-wise fALFF was measured to evaluate regional cerebral function. Regions with differences in fALFF between DS and NDS patients were used as seed points in whole-brain FC analysis. Partial correlation analysis was conducted to examine associations between the fALFF or the FC of altered regions and neurocognitive assessments. Results: Both patient groups showed decreased fALFF in the sensorimotor area, visual cortex, and frontoparietal pathway, but increased fALFF in the precuneus and middle cingulate gyrus when compared with the HCs. Moreover, the NDS group demonstrated higher fALFF than HCs in the left thalamus, caudate, and hippocampus. Compared with the NDS group, the fALFF of the visual cortex was specifically increased, but that of the bilateral insula, the anterior cingulate gyrus (ACG), and the regions extended to the frontotemporal cortex was decreased in the DS group. Numerous abnormal FCs of nerve pathways were found between the two patient groups, mainly concentrated in the frontooccipital, frontotemporal, insula-visual cortex, as well as the temporooccipital pathway. Correlation analysis indicated that, in the DS group, the FC value between the left insula and the visual cortex was positively correlated with cognitive flexibility. In the NDS group, the fALFF of the right insula was negatively correlated with speech fluency, and the FC value between the ACG and the visual cortex was positively correlated with visual spatial memory. Conclusion: The present study demonstrates different altered patterns of fALFF and FC between male patients with DS and NDS. The specific altered regions of the salience network (SN) associated with impaired neurocognition in male DS patients suggest novel insights into the pathogenesis of cognitive impairment in schizophrenia.

Project description:Background and purposePrevious studies have focused on the changes of dynamic and static functional connections in cerebral small vessel disease (CSVD). However, the dynamic characteristics of local brain activity are poorly understood. The purpose of this study was to investigate the dynamic cerebral activity changes in patients with CSVD using the dynamic amplitude of low-frequency fluctuation (d-ALFF).MethodsA total of 104 CSVD patients with cognitive impairment (CSVD-CI, n = 52) or normal cognition (CSVD-NC, n = 52) and 63 matched healthy controls (HCs) were included in this study. Every participant underwent magnetic resonance imaging scans and a battery of neuropsychological examinations. The dynamics of spontaneous brain activity were assessed using dynamic changes in the amplitude of low-frequency fluctuation (ALFF) with the sliding-window method. We used voxel-wise one-way analysis of variance (ANOVA) to compare dynamic ALFF variability among the three groups. Post-hoc t-tests were used to evaluate differences between each group pair. Finally, the brain regions with d-ALFF values with differences between CSVD subgroups were taken as regions of interest (ROI), and the d-ALFF values corresponding to the ROI were extracted for partial correlation analysis with memory.Results(1) There was no significant difference in age (p = 0.120), sex (p = 0.673) and education (p = 0.067) among CSVD-CI, CSVD-NC and HC groups, but there were significant differences Prevalence of hypertension and diabetes mellitus among the three groups (p < 10-3). There were significant differences in scores of several neuropsychological scales among the three groups (p < 10-3). (2) ANOVA and post-hoc t-test showed that there were dynamic abnormalities of spontaneous activity in several brain regions in three groups, mainly located in bilateral parahippocampal gyrus and bilateral hippocampus, bilateral insular and frontal lobes, and the static activity abnormalities in bilateral parahippocampal gyrus and bilateral hippocampal regions were observed at the same time, suggesting that bilateral parahippocampal gyrus and bilateral hippocampus may be the key brain regions for cognitive impairment caused by CSVD. (3) The correlation showed that d-ALFF in the bilateral insular was slightly correlated with the Mini-Mental State Examination (MMSE) score and disease progression rate. The d-ALFF value of the left postcentral gyrus was negatively correlated with the Clock Drawing Test (CDT) score (r = -0.416, p = 0.004), and the d-ALFF value of the right postcentral gyrus was negatively correlated with the Rey's Auditory Verbal Learning Test (RAVLT) word recognition (r = -0.320, p = 0.028).ConclusionThere is a wide range of dynamic abnormalities of spontaneous brain activity in patients with CSVD, in which the abnormalities of this activity in specific brain regions are related to memory and execution or emotion.

Project description:BackgroundStatic changes in local brain activity in patients suffering from amyotrophic lateral sclerosis (ALS) have been studied. However, the dynamic characteristics of local brain activity are poorly understood. Whether dynamic alterations could differentiate patients with ALS from healthy controls (HCs) remains unclear.MethodsA total of 54 patients with ALS (mean age = 48.71 years, male/female = 36/18) and 54 (mean age = 48.30 years, male/female = 36/18) HCs underwent magnetic resonance imaging scans. To depict static alterations in cortical activity, amplitude of low-frequency fluctuations (ALFF) which measures the total power of regional activity was computed. Dynamic ALFF (d-ALFF) from all subjects was calculated using a sliding-window approach. Statistical differences in ALFF and d-ALFF between both groups were used as features to explore whether they could differentiate ALS from HC through support vector machine method.ResultsIn contrast with HCs, patients with ALS displayed increased ALFF in the right inferior temporal gyrus and bilateral frontal gyrus and decreased ALFF in the left middle occipital gyrus and left precentral gyrus. Furthermore, patients with ALS demonstrated lower d-ALFF in widespread regions, including the right lingual gyrus, left superior temporal gyrus, bilateral precentral gyrus, and left paracentral lobule by comparison with HCs. In addition, the ALFF in the left superior orbitofrontal gyrus had a tendency of correlation with ALSFRS-R score and disease progression rate. The classification performance in distinguishing ALS was higher with both features of ALFF and d-ALFF than that with a single approach.ConclusionsDecreased dynamic brain activity in the precentral gyrus, paracentral gyrus, lingual gyrus, and temporal regions was found in the ALS group. The combined ALFF and d-ALFF could distinguish ALS from HCs with a higher accuracy than ALFF and d-ALFF alone. These findings may provide important evidence for understanding the neuropathology underlying ALS.

Project description:ObjectiveFunctional magnetic resonance imaging (fMRI) has been used for evaluating residual brain function and predicting the prognosis of patients with severe traumatic brain injury (sTBI). This study aimed to integrate the fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) to investigate the mechanism and prognosis of patients with sTBI.MethodsSixty-five patients with sTBI were included and underwent fMRI scanning within 14 days after brain injury. The patient's outcome was assessed using the Glasgow Outcome Scale-Extended (GOSE) at 6 months post-injury. Of the 63 patients who met fMRI data analysis standards, the prognosis of 18 patients was good (GOSE scores ≥ 5), and the prognosis of 45 patients was poor (GOSE scores ≤ 4). First, we apply fALFF to identify residual brain functional differences in patients who present different prognoses and conjoined it in regions of interest (ROI)-based FC analysis to investigate the residual brain function of sTBI at the acute phase of sTBI. Then, the area under the curve (AUC) was used to evaluate the predictive ability of the brain regions with the difference of fALFF and FC values.ResultsPatients who present good outcomes at 6 months post-injury have increased fALFF values in the Brodmann area (7, 18, 31, 13, 39 40, 42, 19, 23) and decreased FC values in the Brodmann area (28, 34, 35, 36, 20, 28, 34, 35, 36, 38, 1, 2, 3, 4, 6, 13, 40, 41, 43, 44, 20, 28 35, 36, 38) at the acute phase of sTBI. The parameters of these alterations can be used for predicting the long-term outcomes of patients with sTBI, of which the fALFF increase in the temporal lobe, occipital lobe, precuneus, and middle temporal gyrus showed the highest predictive ability (AUC = 0.883).ConclusionWe provide a compensatory mechanism that several regions of the brain can be spontaneously activated at the acute phase of sTBI in those who present with a good prognosis in the 6-month follow-up, that is, a destructive mode that increases its fALFF in the local regions and weakens its FC to the whole brain. These findings provide a theoretical basis for developing early intervention targets for sTBI patients.

Dataset Information

Characterizing dynamic amplitude of low-frequency fluctuation and its relationship with dynamic functional connectivity: An application to schizophrenia.

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Characterizing dynamic amplitude of low-frequency fluctuation and its relationship with dynamic functional connectivity: An application to schizophrenia.

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