Differences In Amplitude Of Low-frequency Fluctuation Research Articles

Altered brain spontaneous activity in patients with cerebral small vessel disease using the amplitude of low-frequency fluctuation of different frequency bands.

Previous studies showed that cerebral small vessel disease (cSVD) is a leading cause of cognitive decline in elderly people and the development of Alzheimer's disease. Although brain structural changes of cSVD have been documented well, it remains unclear about the properties of brain intrinsic spontaneous activity in patients with cSVD. We collected resting-state fMRI (rs-fMRI) and T1-weighted 3D high-resolution brain structural images from 41 cSVD patients and 32 healthy controls (HC). By estimating the amplitude of low-frequency fluctuation (ALFF) under three different frequency bands (typical band: 0.01-0.1 Hz; slow-4: 0.027-0.073 Hz; and slow-5: 0.01-0.027 Hz) in the whole-brain, we analyzed band-specific ALFF differences between the cSVD patients and controls. The cSVD patients showed uniformly lower ALFF than the healthy controls in the typical and slow-4 bands (pFWE < 0.05). In the typical band, cSVD patients showed lower ALFF involving voxels of the fusiform, hippocampus, inferior occipital cortex, middle occipital cortex, insula, inferior frontal cortex, rolandic operculum, and cerebellum compared with the controls. In the slow-4 band, cSVD patients showed lower ALFF involving voxels of the cerebellum, hippocampus, occipital, and fusiform compared with the controls. However, there is no significant between-group difference of ALFF in the slow-5 band. Moreover, we found significant "group × frequency" interactions in the left precuneus. Our results suggested that brain intrinsic spontaneous activity of cSVD patients was abnormal and showed a frequency-specific characteristic. The ALFF in the slow-4 band may be more sensitive to detecting a malfunction in cSVD patients.

Transcriptional correlates of frequency-dependent brain functional activity associated with symptom severity in degenerative cervical myelopathy

BackgroundNeuroimaging techniques provide insights into the brain abnormalities secondary to degenerative cervical myelopathy (DCM) and their association with neurological deficits. However, the neural correlates underlying the discrepancy between symptom severity and the degree of spinal cord compression, as well as the transcriptional correlates of these cortical abnormalities, remain unknown in DCM patients. MethodsIn this cross-sectional study, which collected resting-state functional MRI (rs-fMRI) images and the Japanese Orthopedic Association (JOA) score, enrolled 104 participants (54 patients and 50 healthy controls). The frequency-dependent amplitude of low-frequency fluctuation (ALFF) was obtained for all participants. We investigated the ALFF differences between mild-symptom DCM patients and severe-symptom DCM patients while carefully matching the degree of compression between these two groups via both univariate comparison and searchlight classification for three frequency bands (e.g., Slow-4, Slow-5, and Full-band). Additionally, we identified genes associated with symptom severity in DCM patients by linking the spatial patterns of gene expression of Allen Human Brain Atlas and brain functional differences between mild symptom and severe symptom groups. Results(1) We found that the frequency-specific brain activities within the sensorimotor network (SMN), visual network (VN), and default mode network (DMN) were associated with the varying degrees of functional impairment in DCM patients; (2) the frequency-specific brain activity within the SMN correlated with the functional recovery in patients with DCM; (3) a spatial correlation between the brain-wide expression of genes involved in neuronal migration and the brain functional activities associated with symptom severity was identified in DCM patients. ConclusionIn conclusion, our study bridges gaps between genes, cell classes, biological processes, and brain functional correlates of DCM. While our findings are correlational in nature, they suggest that the neural activities of sensorimotor cortices in DCM are associated with the severity of symptoms and might be associated with neuronal migration within the brain.

Altered local spontaneous brain activity pattern in children with right-eye amblyopia of varying degrees: evidence from fMRI.

To investigate the abnormal changes of local brain activity in children with right-eye amblyopia of varying degrees. Data of resting-state functional magnetic resonance imaging were collected from 16 children with severe amblyopia, 17 children with mild to moderate amblyopia, and 15 children with normal binocular vision. Local brain activity was analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo). There were extensive ALFF differences among the three groups in 10 brain regions. There were extensive differences in ReHo among the three groups in 11 brain regions. The ALFF and ReHo of the right orbital part of the middle frontal gyrus displayed a significantly positive correlation with the best-corrected visual acuity of the right eye, respectively. The ALFF value and ReHo value of the right orbital part of the middle frontal gyrus followed the pattern of normal control < mild to moderate amblyopia < severe amblyopia. This study demonstrated that there were changes in specific patterns of ALFF and ReHo in children with right-eye amblyopia of different degrees in brain regions performing visual sensorimotor and attentional control functions.

Genes associated with spontaneous brain activity changes in clinically different patients with major depressive disorder: Atranscription-neuroimaging association study.

The amplitude of low-frequency fluctuations (ALFF) of resting-state functional MRI signals is a reliable neuroimaging measure of spontaneous brain activity. Inconsistent ALFF alterations have been reported in major depressive disorder (MDD) possibly due to clinical heterogeneity. This study was designed to investigate clinically sensitive and insensitive genes associated with ALFF alterations in MDD and the potential mechanisms. Transcription-neuroimaging association analyses of case-control ALFF differences from two independent neuroimaging datasets with gene expression data from Allen Human Brain Atlas were performed to identify the two gene sets. Various enrichment analyses were conducted to characterize their preference in biological functions, cell types, temporal stages, and shared effects with other psychiatric disorders. Compared with controls, first-episode and drug-naïve patients showed more extensive ALFF alterations than patients with varied clinical features. We identified 903 clinically sensitive genes and 633 clinically insensitive genes, and the former was enriched for genes with down-regulated expression in the cerebral cortex of MDD patients. Despite shared functions of cell communication, signaling, and transport, clinically sensitive genes were enriched for cell differentiation and development whereas clinically insensitive genes were for ion transport and synaptic signaling. Clinically sensitive genes showed enrichment for microglia and macrophage from childhood to young adulthood in contrast to clinically insensitive genes for neurons before early infancy. Clinically sensitive genes (15.2%) were less likely correlated with ALFF alterations in schizophrenia than clinically insensitive genes (66.8%), and both were not relevant to bipolar disorder and adult attention deficit and hyperactivity disorder based on a third independent neuroimaging dataset. Present results provide novel insights into the molecular mechanisms of spontaneous brain activity changes in clinically different patients with MDD.

Increased spontaneous activity of the superior frontal gyrus with reduced functional connectivity to visual attention areas and cerebellum in male smokers.

Chronic smokers have abnormal spontaneous regional activity and disrupted functional connectivity as revealed by previous neuroimaging studies. Combining different dimensions of resting-state functional indicators may help us learn more about the neuropathological mechanisms of smoking. The amplitude of low frequency fluctuations (ALFF) of 86 male smokers and 56 male non-smokers were first calculated. Brain regions that displayed significant differences in ALFF between two groups were selected as seeds for further functional connectivity analysis. Besides, we examined correlations between brain areas with abnormal activity and smoking measurements. Increased ALFF in left superior frontal gyrus (SFG), left medial superior frontal gyrus (mSFG) and middle frontal gyrus (MFG) as well as decreased ALFF in right calcarine sulcus were observed in smokers compared with non-smokers. In the seed-based functional connectivity analysis, smokers showed attenuated functional connectivity with left SFG in left precuneus, left fusiform gyrus, left lingual gyrus, left cerebellum 4 5 and cerebellum 6 as well as lower functional connectivity with left mSGF in left fusiform gyrus, left lingual gyrus, left parahippocampal gyrus (PHG), left calcarine sulcus, left cerebellum 4 5, cerebellum 6 and cerebellum 8 (GRF corrected, Pvoxel < 0.005, Pcluster<0.05). Furthermore, attenuated functional connectivity with left mSGF in left lingual gyrus and PHG displayed a negative correlation with FTND scores (r = -0.308, p = 0.004; r = -0.326, p = 0.002 Bonferroni corrected). Our findings of increased ALFF in SFG with reduced functional connectivity to visual attention areas and cerebellum subregions may shed new light on the pathophysiology of smoking.

Frequency-Specific Alterations of Spontaneous Brain Activity in First-Episode Drug-Naïve Schizophrenia

To investigate frequency-specific alterations of spontaneous brain activity in first-episode drug-naïve schizophrenia (SZ) patients and the associations with clinical symptoms. We collected the resting-state functional MRI (rs-fMRI) data from 84 first-episode drug-naïve SZ patients and 94 healthy controls (HCs) and calculated the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) of four frequency bands, including slow-2, slow-3, slow-4, and slow-5. Two-sample t-tests were used to evaluate the intergroup differences in ALFF and ReHo, while partial correlation analyses were conducted to explore the associations between abnormal ALFF and ReHo and the severity of clinical symptoms in the SZ group. Compared with HCs, the SZ group showed reduced ALFF in superior cerebellum and cerebellar vermis across slow-2, slow-3, and slow-4 bands, while increased ALFF was found in left superior temporal gyrus, middle temporal gyrus, and superior temporal pole at slow-4 band. Moreover, reduced ReHo was observed in the right precentral and postcentral gyri at slow-3 band in the SZ group. Additionally, the ALFF of left superior temporal gyrus, middle temporal gyrus, and superior temporal pole in slow-4 band showed a trend of positive correlation with the excited factor score of Positive and Negative Syndrome Scale (PANSS) in the SZ group. Our results suggest that local alterations of spontaneous brain activity were frequency-specific in first-episode drug-naïve SZ patients.

ALFF response interaction with learning during feedback in individuals with multiple sclerosis.

Amplitude of low-frequency fluctuations (ALFF) is defined as changes of BOLD signal during resting state (RS) brain activity. Previous studies identified differences in RS activation between healthy and multiple sclerosis (MS) participants. However, no research has investigated the relationship between ALFF and learning in MS. We thus examine this here. Twenty-five MS and nineteen healthy participants performed a paired-associate word learning task where participants were presented with extrinsic or intrinsic performance feedback. Compared to healthy participants, MS participants showed higher local brain activation in the right thalamus. We also observed a positive correlation in the MS group between ALFF and extrinsic feedback within the left inferior frontal gyrus, and within the left superior temporal gyrus in association with intrinsic feedback. Healthy participants showed a positive correlation in the right fusiform gyrus between ALFF and extrinsic feedback. Findings suggest that while MS participants do not show a feedback learning impairment compared to the healthy participants, ALFF differences might suggest a general maladaptive pattern of task unrelated thalamic activation and adaptive activation in frontal and temporal regions. Results indicate that ALFF can be successfully used at capturing pathophysiological changes in local brain activation in MS in association with learning through feedback.

Amplitude of low frequency fluctuations during resting state fMRI in autistic children.

Resting state fMRI (rs-fMRI) provides an excellent platform for examining the amplitude of low frequency fluctuations (ALFF) and fractional amplitude of low frequency fluctuations (fALFF), which are key indices of brain functioning. However, ALFF and fALFF have been used only sporadically to study autism. rs-fMRI data from 69 children (40 autistic, mean age=8.47 ± 2.20 years; age range: 5.2 to 13.2; and 29 non-autistic, mean age=9.02 ± 1.97 years; age range 5.9 to 12.9) were obtained from the Autism Brain Imaging Data Exchange (ABIDE II). ALFF and fALFF were measured using CONN connectivity toolbox and SPM12, at whole-brain & network-levels. A two-sampled t-test and a 2 Group (autistic, non-autistic) × 7 Networks ANOVA were conducted to test group differences in ALFF and fALFF. The whole-brain analysis identified significantly reduced ALFF values for autistic participants in left parietal opercular cortex, precuneus, and right insula. At the network level, there was a significant effect of diagnostic group and brain network on ALFF values, and only significant effect of network, not group, on fALFF values. Regression analyses indicated a significant effect of age on ALFF values of certain networks in autistic participants. Such intrinsically different network-level responses in autistic participants may have implications for task-level recruitment and synchronization of brain areas, which may in turn impact optimal cognitive functioning. Moreover, differences in low frequency fluctuations of key networks, such as the DMN and SN, may underlie alterations in brain responses in autism that are frequently reported in the literature.

Frequency-specific alterations in intrinsic low-frequency oscillations in newly diagnosed male patients with obstructive sleep apnea.

PurposePrevious studies found abnormal low-frequency spontaneous brain activity related to cognitive impairment in patients with obstructive sleep apnea (OSA). However, it is unclear if low-frequency spontaneous brain activity is related to specific frequency bands in OSA patients. In this study, we used the amplitude of low-frequency fluctuation (ALFF) method in patients with OSA to explore characteristics of spontaneous brain activity in the classical (0.01–0.1 Hz) and five sub-frequency bands (slow-2 to slow-6) and analyzed the relationship between spontaneous brain activity and clinical evaluation was analyzed.Patients and methodsResting-state magnetic resonance imaging data and clinical assessments were collected from 52 newly-diagnosed OSA patients and 62 healthy controls (HCs). We calculated the individual group ALFF values in the classical and five different sub-frequency bands. A two-sample t-test compared ALFF differences, and one-way analysis of variance explored interactions in frequency bands between the two groups.ResultsALFF values in the OSA group were lower than those in the HC group in the bilateral precuneus/posterior cingulate cortex, bilateral angular gyrus, left inferior parietal lobule, brainstem, and right fusiform gyrus. In contrast, ALFF values in the OSA group were higher than those in the HC group in the bilateral cerebellum posterior lobe, bilateral superior frontal gyrus, bilateral middle frontal gyrus, left inferior frontal gyrus, left inferior temporal gyrus, and left fusiform gyrus. Some ALFF values in altered brain regions were associated with body mass index, apnea-hypopnea index, neck circumference, snoring history, minimum SaO2, average SaO2, arousal index, oxygen reduction index, deep sleep period naming, abstraction, and delayed recall in specific frequency bands.ConclusionOur results indicated the existence of frequency-specific differences in spontaneous brain activity in OSA patients, which were related to cognitive and other clinical symptoms. This study identified frequency-band characteristics related to brain damage, expanded the cognitive neuroimaging mechanism, and provided additional OSA neuroimaging markers.

Altered Regional Homogeneity and Amplitude of Low-Frequency Fluctuations Induced by Electroconvulsive Therapy for Adolescents with Depression and Suicidal Ideation.

Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the effects of electroconvulsive therapy (ECT) causing brain function changes in adolescents who suffered from depression and suicidal ideation (SI). A total of 30 patients (MDDs) and 25 healthy controls (HCs) matched by gender, age, and education level were enrolled. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were used to compare differences between HCs and MDDs at baseline, and differences in ALFF and ReHo pre/post ECT in MDDs. Pearson correlation analysis was used to evaluate the relationship between altered brain function and clinical symptoms. At baseline, MDDs showed decreased ALFF in the left inferior temporal gyrus and right amygdala, decreased ReHo in left inferior temporal gyrus, and increased ReHo in the right inferior frontal gyrus, opercular part and left middle occipital gyrus. After ECT, MDDs showed increased ALFF in the right middle occipital gyrus, decreased ALFF in left temporal pole, left inferior frontal gyrus, opercular part, and right frontal middle gyrus, increased ReHo in the right middle occipital gyrus, and left inferior temporal gyrus. Pearson correlation found HAMD scores at baseline were negatively correlated with ALFF in the left inferior temporal gyrus, and HAMD and BSSI scores after ECT were negatively correlated with ALFF in the right middle occipital gyrus. The abnormal activities of amygdala, inferior temporal gyrus and middle occipital gyrus might be related to depressive and suicidal symptoms in adolescents.

Identifying and validating subtypes of Parkinson's disease based on multimodal MRI data via hierarchical clustering analysis.

ObjectiveWe wished to explore Parkinson's disease (PD) subtypes by clustering analysis based on the multimodal magnetic resonance imaging (MRI) indices amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV). Then, we analyzed the differences between PD subtypes.MethodsEighty-six PD patients and 44 healthy controls (HCs) were recruited. We extracted ALFF and GMV according to the Anatomical Automatic Labeling (AAL) partition using Data Processing and Analysis for Brain Imaging (DPABI) software. The Ward linkage method was used for hierarchical clustering analysis. DPABI was employed to compare differences in ALFF and GMV between groups.ResultsTwo subtypes of PD were identified. The “diffuse malignant subtype” was characterized by reduced ALFF in the visual-related cortex and extensive reduction of GMV with severe impairment in motor function and cognitive function. The “mild subtype” was characterized by increased ALFF in the frontal lobe, temporal lobe, and sensorimotor cortex, and a slight decrease in GMV with mild impairment of motor function and cognitive function.ConclusionHierarchical clustering analysis based on multimodal MRI indices could be employed to identify two PD subtypes. These two PD subtypes showed different neurodegenerative patterns upon imaging.

Effects of the Prolong Life With Nine Turn Method (Yan Nian Jiu Zhuan) Qigong on Brain Functional Changes in Patients With Chronic Fatigue Syndrome in Terms of Fatigue and Quality of Life.

BackgroundChronic fatigue syndrome (CFS) is characterized by persistent fatigue, which often leads to physical and psychological damage. The Prolong Life with Nine Turn method (PLWNT) Qigong is considered as one of the complementary treatments for improving symptoms in patients with CFS. In this study, we used functional magnetic resonance imaging (fMRI) to explore the effects of PLWNT intervention on the subjects with CFS.MethodsThirty four CFS patients were randomly divided into PLWNT group and cognitive behavioral therapy (CBT) group. Both groups were taught by a highly qualified professor at the Shanghai University of Traditional Chinese Medicine once a week and were supervised online during the remaining 6 days at home, over 12 consecutive weeks. We calculated the regional rs-fMRI index amplitude of low-frequency fluctuations (ALFF) for all subjects. To study the changes of the brain network, we used the brain regions with significant differences in ALFF as the regions of interest for whole-brain functional connectivity (FC) analysis. The Multi-dimensional Fatigue Inventory 20 (MFI-20) and Short Form 36-item Health Survey (SF-36) were used for clinical symptom assessment to explore the possible correlation between the rs-fMRI indicators and clinical variations.ResultsThe ALFF values of the right superior frontal gyrus (SFG), and left median cingulate gyrus (DCG) were increased, whereas those of the left middle occipital gyrus (OG), right middle OG and left middle temporal gyrus (MTG) were decreased in PLWNT group. The FC values between the DCG and middle temporal gyrus (MTG), and those between the left OG and the right OG were enhanced. In addition, the SF-36 were positively with the left OG (r = 0.524), SFG (r = 0.517), and DCG (r = 0.533), MFI-20 were negatively with the SFG (r = −0.542) and DCG (r = −0.578). These results were all corrected by FWE (voxel level p < 0.001, cluster level p < 0.05).ConclusionCFS patients have abnormal regional spontaneous neuronal activity and abnormal functional connections between regions after PLWNT intervention. PLWNT can relieve the fatigue symptoms of CFS patients and improve their quality of life. The study was registered in the American Clinical Trial Registry (12/04/2018). Registration Number is NCT03496961.

Brain Under Fatigue - Can Perceived Fatigability in Multiple Sclerosis Be Seen on the Level of Functional Brain Network Architecture?

BackgroundFatigue is one of the most common symptoms of multiple sclerosis (MS), significantly affecting the functioning of the patients. However, the neural underpinnings of physical and mental fatigue in MS are still vague. The aim of our study was to investigate the functional architecture of resting-state networks associated with fatigue in patients with MS.MethodsThe sum of 107 high-functioning patients underwent a resting-state scanning session and filled out the 9-item Fatigue Severity Scale (FSS). Based on the FSS score, we identified patients with different levels of fatigue using the cluster analysis. The low-fatigue group consisted of n = 53 subjects, while the high-fatigue group n = 48. The neuroimaging data were analyzed in terms of functional connectivity (FC) between various resting-state networks as well as amplitude of low-frequency fluctuation (ALFF) and fractional amplitude of low-frequency fluctuations (fALFF).ResultsTwo-sample t-test revealed between-group differences in FC of posterior salience network (SN). No differences occurred in default mode network (DMN) and sensorimotor network (SMN). Moreover, differences in fALFF were shown in the right middle frontal gyrus and right superior frontal gyrus, however, no ALFF differences took place.ConclusionCurrent study revealed significant functional network (FN) architecture between-group differences associated with fatigue. Present results suggest the higher level of fatigue is related to deficits in awareness as well as higher interoceptive awareness and nociception.

Associations between polygenic risk scores and amplitude of low-frequency fluctuation of inferior frontal gyrus in schizophrenia

Schizophrenia (SCZ) is a serious and complex mental disorder with high heritability. Polygenic risk score (PRS) is a useful tool calculating the accumulating effects of multiple common genetic variants of schizophrenia. The amplitude of low-frequency fluctuation (ALFF) is an efficient index to reflect spontaneous, intrinsic neuronal activity. Aberrant ALFF of brain regions were reported in schizophrenia frequently, but the relationship between PRS and ALFF has not been studied. In the present study, we compared PRS and ALFF in 101 schizophrenia patients and 106 age-matched healthy controls to test their associations with schizophrenia. Then, the correlation of PRS with ALFF was measured to reveal the effect of polygenic risk on brain activity in schizophrenia. We found that schizophrenia patients showed significant differences in PRS and ALFF compared with controls. Twenty-six brain regions showed significant difference of ALFF between schizophrenia cases and controls, of which left inferior frontal gyrus, triangular part (IFGtriang.L) showed increased activity in schizophrenia. PRS-SCZ was positively correlated with ALFF in IFGtriang.L in 57 non-chronic patients. Genes involved in synaptic organization and transmission, especially in glutamatergic synapse, were highly enriched in PRS-SCZ genes, suggesting the dysfunction of synapses in schizophrenia. These results help to understand the molecular mechanism underlying schizophrenia and related brain dysfunction.

Comparing Brain Functional Activities in Patients With Blepharospasm and Dry Eye Disease Measured With Resting-State fMRI.

Background: Blepharospasm (BSP) and dry eye disease (DED) are clinically common diseases characterized by an increased blinking rate. A sustained eyelid muscle activity may alter the cortical sensorimotor concordance and lead to secondary functional changes. This study aimed to explore the central mechanism of BSP by assessing brain functional differences between the two groups and comparing them with healthy controls.Methods: In this study, 25 patients with BSP, 22 patients with DED, and 23 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) scan. The amplitude of low-frequency fluctuations (ALFF) was applied to analyze the imaging data.Results: Analysis of covariance (ANCOVA) revealed widespread differences in ALFF across the three groups. In comparison with healthy controls, patients with BSP showed abnormal ALFF in the sensorimotor integration related-brain regions, including the bilateral supplementary motor area (SMA), left cerebellar Crus I, left fusiform gyrus, bilateral superior medial prefrontal cortex (MPFC), and right superior frontal gyrus (SFG). In comparison with patients with DED, patients with BSP exhibited a significantly increased ALFF in the left cerebellar Crus I and left SMA. ALFF in the left fusiform gyrus/cerebellar Crus I was positively correlated with symptomatic severity of BSP.Conclusions: Our results reveal that the distinctive changes in the brain function in patients with BSP are different from those in patients with DED and healthy controls. The results further emphasize the primary role of sensorimotor integration in the pathophysiology of BSP.

Amplitude of low-frequency fluctuation (ALFF) alterations in adults with subthreshold depression after physical exercise: A resting-state fMRI study

BackgroundPhysical exercise has been proved to reduce the risk of major depression in Subthreshold depression (StD) individuals effectively, yet little is known about the spontaneous brain activity changes associated with physical exercise. MethodsA total of 70 adult subjects, including 38 StD and 32 healthy control (HC) subjects, underwent a resting-state functional magnetic resonance imaging (rs-fMRI) before and after eight-week aerobic exercise respectively. Then, the amplitude of low-frequency fluctuation (ALFF) alterations between the two groups were quantitatively analyzed. ResultsBefore exercise intervention, the rs-fMRI data showed increased ALFF of the right putamen in the StD group compared with HC group. After exercise intervention, there was no significant ALFF change observed between the StD and HC groups. The longitudinal ALFF differences from pre- to post- exercise intervention showed significantly decreased ALFF in the right middle and inferior occipital gyrus, right middle and inferior temporal gyrus, right fusiform gyrus (FG), while increased ALFF in the right middle cingulate, right superior parietal louble, right inferior parietal lobule (IPL) (inferior parietal gyrus and supramarginal gyrus), and bilateral precuneus in the StD group. As for HC group, the results showed that decreased ALFF in the right FG and right parahippocampus, while increased ALFF in the right precuneus, right middle cingulate, right supplementary motor area, right superior parietal lobule and right paracentral lobule in the HC group. No significant correlation between changes of ALFF and clinical scale scores in the StD group. LimitationsThe definitions of StD are varied in terms of different studies, the final sample size was relatively small, and the age range of the subjects in this study was narrow. Meanwhile, the exercise intervention trial was short-term. ConclusionsThese results further support the standpoint that physical exercise has the potential to reshape the abnormal patterns of spontaneous brain activity in adults with StD.

Different cerebral functional segregation in Sjogren's syndrome with or without systemic lupus erythematosus revealed by amplitude of low-frequency fluctuation.

Sjögren's syndrome (SjS) associated with systemic lupus erythematosus (SjS-SLE) was considered a standalone but often-overlooked entity. To assess altered spontaneous brain activity in SjS-SLE and SjS using amplitude of low-frequency fluctuation (ALFF). Sixteen patients with SjS-SLE, 17 patients with SjS, and 17 matched controls underwent neuropsychological tests and subsequent resting-state functional magnetic resonance imaging (fMRI) examinations. The ALFF value was calculated based on blood oxygen level dependent (BOLD) fMRI. Statistical parametric mapping was utilized to analyze between-group differences and multiple comparison was corrected with Analysis of Functional NeuroImages 3dClustSim. Then, the ALFFs of brain regions with significant differences among the three groups were correlated to corresponding clinical and neuropsychological variables by Pearson correlation. ALFF differences in the bilateral precuneus/posterior cingulate cortex (PCC), right parahippocampal gyrus/caudate/insula, and left insula were found among the three groups. Both SjS-SLE and SjS displayed decreased ALFF in the right parahippocampal gyrus, right insula, and left insula than HC. Moreover, SjS-SLE showed wider decreased ALFF in the bilateral precuneus and right caudate, while the SjS group exhibited increased ALFF in the bilateral PCC. Additionally, patients with SjS-SLE exhibited lower ALFF values in the bilateral PCC and precuneus than SjS. Moreover, ALFF values in the right parahippocampal gyrus and PCC were negatively correlated to fatigue score and disease duration, respectively, in SjS-SLE. SjS-SLE and SjS exhibited common and different alteration of cerebral functional segregation revealed by AlFF analysis. This result appeared to indicate that SjS-SLE might be different from SjS with a neuroimaging standpoint.

Brain Functional and Structural Alterations in Women With Bipolar Disorder and Suicidality.

Objective: Suicide is the leading cause of death from bipolar disorder (BD). At least 25–50% of the patients with BD will attempt suicide, with suicide rates much higher in women patients than in men. It is crucial to explore the potential neural mechanism underlying suicidality in women with BD, which will lead to understanding and detection of suicidality and prevent death and injury from suicide.Methods: Brain function and structure were measured by amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV) in 155 women [30 women with BD and a history of suicidality, 50 women with BD without suicidality, and 75 healthy controls (HC)]. The differences in ALFF and GMV across the BD with suicidality, BD without suicidality, and HC groups were investigated.Results: BD with suicidality showed significantly increased ALFF in the left and right cuneus compared with BD without suicidality and HC groups. Moreover, the GMV in the left lateral prefrontal cortex and left cuneus in BD with suicidality were significantly lower than those in BD without suicidality and HC groups, while the GMV of the right ventral prefrontal cortex was significantly decreased in both BD with and without suicidality groups.Conclusions: This study, combining functional and structural neuroimaging techniques, may help to identify specific pathophysiological changes in women with BD and suicidality. Increased ALFF and less GMV in cuneus might represent the neuroimaging features of suicidality in women with BD. Investigating this potential neuromarker for suicidality in women with BD may lead to the ability to prevent suicidality.

Resting-State Functional Connectivity and Anxiety Predict Relapse in Remitted Late-Life Depression

<h3>Introduction</h3> Late-life depression (LLD) refers to depression occurring in older age and is associated with a multitude of psychosocial and biological factors, including conditions related to pathological aging, including cardiovascular and cerebrovascular diseases, and dementia. Relevant psychosocial factors comprise personality disorders, neuroticism, trauma and stress. Depending on the relative contribution of conditions related to pathological aging versus psychosocial factors, some patients may not respond to antidepressants and others may be prone to relapse even when they achieved initial remission on an antidepressant. The neural mechanisms related to recurrence of LLD are not clear. About 50% of individuals who have recovered from a first episode of depression will suffer from at least one additional episode. Therefore, identifying patients prone to relapse is important for developing tailored treatment regimens, preventing suicide, and reducing economic burdens and other morbidities. To understand the neural mechanisms related to relapse of depression, and identify neuroimaging markers to predict individuals who tend to relapse, we conducted a secondary data analysis on clinical and fMRI data collected from our NBOLD project. We hypothesized that, compared with individuals who did not relapse during a two-year clinical follow-up period, those who relapsed would show significantly altered resting-state activity patterns in core neural networks related to LLD including the default mode, executive control and salience networks. <h3>Methods</h3> The sample included 102 adults with LLD who were free of medication for at least two weeks before study enrollment. Depression severity was measured by MADRS and was assessed by a study psychiatrist at each study visit, which occurred frequently while the subject remained depressed and quarterly when remission was achieved. Among the enrolled participants, 52 (age range of 60 – 89) achieved depression remission after antidepressant treatment (MADRS< 8 for at least 2 months). We defined relapse as having a MADRS > 15 for at least two weeks. Individuals were classified as non-relapsed if they maintained a MADRS <13 after remission during the two follow-up years. Among the 52 LLD patients, 27 of them relapsed and 25 did not. We also measured trait and state anxiety and neuroticism using State-Trait Anxiety Inventory (STAI), NEO Personality Inventory (NEO PI). The neuroimaging data was collected from 3T Siemens Skyra scanner. The imaging parameters for T1-weighted images were: TR/TE=2200/2.8ms, flip angle=13^o, matrix = 256 × 256 × 169, voxelsize=1 × 1 × 1mm³. The 7-min resting-state fMRI data was collected using EPI sequence with FOV=240mm, flip angle=90^o, TR/TE=2000/31ms, matrix=64 × 64 × 34, voxelsize=3.8 × 3.8 × 3.75mm³. The resting-state fMRI data was preprocessed using the default protocol settings in Conn Toolbox version17f. The preprocessed data was entered to DPABI software for calculating the Amplitude of Low-Frequency Fluctuations (ALFF). Functional connectivity (FC) was done using Conn Toolbox version17f. Two sample t-tests were conducted to compare resting-state activity, ALFF, and FC to examine differences in ALFF and FC between relapsed and non-relapsed LLD groups (age and gender were controlled). Significance was set at p<0.05 with FDR correction for multiple comparisons. <h3>Results</h3> There were no significant differences between relapsed and non-relapsed groups in age, gender, state anxiety or neuroticism. Those who relapsed during the two-year follow-up had less severe depressive symptoms at baseline (mean (SD) MADRS=18.40(4.06) than those non-depressed group (mean (SD) MADRS=20.81(6.23) with p=0.001), whereas the relapsed group had higher STAI-trait anxiety than the non-relapsed group (p=0.04). Two-sample t-tests on FC showed that the relapsed group had a lower FC between the right parahippocampus and the superior and inferior parietal cortex. The relapsed group also had a reduced FC between the right globus pallidum and the right superior frontal gyrus. In addition, the relapsed group had significantly greater ALFF in the left amygdala and globus pallidum compared with the non-relapsed group; however, the significance was lost after controlling for depression severity and STAI-trait anxiety. <h3>Conclusions</h3> This is one of few studies that have examined clinical and neural characters in relapsed LLD. Lower FC between the right parahippocampus and the superior and inferior parietal cortex suggests a potential reduction in attention for memory. Low FC between the right globus pallidum and the right superior frontal gyrus may indicate reduced executive function in relapsed individuals. Importantly, the relapsed group also showed lower depressive symptoms yet higher trait anxiety. These results suggest that depression comorbid with anxiety might be an essential factor of relapse tendency. Future studies will examine whether the relapsed group also has lower executive function.

Brain functional changes in perimenopausal women: an amplitude of low-frequency fluctuation study.

Objective:To evaluate the effects of sex hormones on amplitude of low-frequency fluctuation (ALFF) in brain regions related to cognition in perimenopausal women.Methods:This cross-sectional study involved 25 perimenopausal women and 25 premenopausal women who underwent behavioral evaluations, sex hormone level measurements, and functional magnetic resonance imaging (fMRI). All data and ALFF analyses were preprocessed using the Data Processing Assistant for Resting-State fMRI. Statistical analyses were performed using the Resting-State fMRI Data Analysis Toolkit to explore the differences in ALFF between perimenopausal and premenopausal women. The gray matter volume (GMV) values extracted from brain regions (regions of interest) with significantly different ALFF values between the perimenopausal and premenopausal groups were compared. We analyzed the correlations of the ALFF and GMV values of these regions of interest with the results of behavioral evaluations and sex hormone levels in the two groups.Results:Compared with the premenopausal group, the perimenopausal group showed significant ALFF increase in the left gyrus rectus. Regions with decreased ALFF in the perimenopausal group included the left superior temporal gyrus, left inferior frontal gyrus, and left insula. The GMV values of the left gyrus rectus and left superior temporal gyrus were reduced in perimenopausal women. Furthermore, the estradiol level was negatively correlated with the ALFF value of the left gyrus rectus in perimenopausal women.Conclusions:The ALFF and GMV values of certain brain regions related to cognitive function were changed in perimenopausal women. Such functional brain alterations may provide more information regarding the mechanism of cognitive dysfunction in perimenopausal women.