Functional Abnormality of the Reward System in Depressed Adolescents and Young Adults with and without Suicidal Behavior.

OBJECTIVE: To identify local and functional connectivity abnormalities in the brain's reward network in depressed adolescents and young adults with and without suicidal behavior. METHODS: Magnetic resonance imaging data were obtained from 41 major depressive disorder (MDD) patients with suicidal behavior (sMDD, males/females: 12/29), 44 MDD patients without suicidal behavior (nMDD, males/females: 13/32), and 52 healthy controls (HCs, males/females: 17/35). The Young Mania Scale, Hamilton Depression Scale, Columbia Suicide Scale, and Scale for Suicide Ideation were used to evaluate emotional state and suicidal ideation and behaviors. The amplitude of low frequency fluctuations (ALFF), regional homogeneity (ReHo) and functional connectivity of 11 regions of interest (ROIs) in the reward network were determined. RESULTS: ALFF values in the vmPFC of the nMDD group were significantly lower than those in the HC group (p = 0.031). The ReHo values of the nMDD group were lower in the lVS but higher in the vmPFC than those of the HC group (P = 0.018 and 0.025, respectively). Functional connectivity of the AC with the vmPFC, lVS, rVS, and vmPFC was increased in the sMDD group compared with that in the nMDD group (P = 0.038, 0.034, 0.006, respectively). CONCLUSION: Local and functional connectivity abnormalities in the reward network were found in the MDD groups. However, increased functional connectivity was found in only the sMDD group.

Abnormalities of regional brain activity and executive function in patients with temporal lobe epilepsy: A cross-sectional and longitudinal resting-state functional MRI study.

PURPOSE: We decided to track changes in regional brain activity and executive function in temporal lobe epilepsy (TLE) patients based on cross-sectional and longitudinal designs and sought potential imaging features for follow-up observation. METHODS: Thirty-two TLE patients and thirty-three healthy controls (HCs) were recruited to detect changes in fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) and to evaluate executive function both at baseline and at two-year (23.3 ± 8.3 months) follow-up. Moreover, multivariate pattern analysis (MVPA) was used for follow-up observation. RESULTS: TLE patients displayed lower fALFF values in the right superior frontal gyrus (SFG) and higher ReHo values in the left putamen (PUT) relative to the HCs. Longitudinal analysis revealed that TLE patients at follow-up exhibited higher fALFF values in the left postcentral gyrus (PoCG), higher ReHo values in the left PoCG and the right middle frontal gyrus (MFG), lower ReHo values in the bilateral PUT and the right fusiform gyrus (FFG) compared with these patients at baseline. The executive function was impaired in TLE patients but didn't deteriorate over time. No correlations were discovered between regional brain activity and executive function. The MVPA based on ReHo performed well in differentiating the follow-up group from the baseline group. CONCLUSION: We revealed the abnormalities in regional brain activity and executive function as well as their longitudinal trends in TLE patients. The ReHo might be a good imaging feature for follow-up observation.

Maternal psychological distress associates with alterations in resting-state low-frequency fluctuations and distal functional connectivity of the neonate medial prefrontal cortex.

Prenatal stress exposure (PSE) has been observed to exert a programming effect on the developing infant brain, possibly with long-lasting consequences on temperament, cognitive functions and the risk for developing psychiatric disorders. Several prior studies have revealed that PSE associates with alterations in neonate functional connectivity in the prefrontal regions and amygdala. In this study, we explored whether maternal psychological symptoms measured during the 24th gestational week had associations with neonate resting-state network metrics. Twenty-one neonates (nine female) underwent resting-state fMRI scanning (mean gestation-corrected age at scan 26.95 days) to assess fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo). The ReHo/fALFF maps were used in multiple regression analysis to investigate whether maternal self-reported anxiety and/or depressive symptoms associate with neonate functional brain features. Maternal psychological distress (composite score of depressive and anxiety symptoms) was positively associated with fALFF in the neonate medial prefrontal cortex (mPFC). Anxiety and depressive symptoms, assessed separately, exhibited similar but weaker associations. Post hoc seed-based connectivity analyses further showed that distal connectivity of mPFC covaried with PSE. No associations were found between neonate ReHo and PSE. These results offer preliminary evidence that PSE may affect functional features of the developing brain during gestation.

Altered brain spontaneous and synchronization activity in latent autoimmune diabetes in adults: A resting-state functional MRI study.

AIMS: This study aimed to explore the clinical features and spontaneous brain activity among patients with latent autoimmune diabetes in adults (LADA) and to investigate the relationship among these characteristics. METHODS: We conducted a cross-sectional study using cognitive assessments and resting-state functional magnetic resonance imaging (rs-fMRI) to evaluate the cognitive function and brain activities of healthy controls (HCs) and patients with LADA. Functional connectivity (FC) analysis was performed on the brain regions that showed significantly different activation in regional homogeneity (ReHo) analysis between the two groups. Furthermore, a linear regression model was conducted for the association between metabolism and cognition. RESULTS: This study enrolled patients with LADA (and age-, sex-, and education-matched HCs). Patients with LADA had worse cognitive status at the general level and poorer memory than controls. Rs-fMRI analysis among patients with LADA showed decreased ReHo values in the right occipital lobe and temporal lobe and decreased seed-based FC in the right parietal lobe compared to those of controls. The seed-based FC values in the right parietal lobe were positively associated with word fluency and processing speed in patients with LADA. Furthermore, low-density lipoprotein cholesterol was negatively correlated with Montreal Cognitive Assessment scores in patients with LADA. CONCLUSIONS: Patients with LADA had worse cognitive function and decreased spontaneous brain activity in the temporal lobe and occipital lobe compared to controls. Moreover, glycolipid metabolism was closely related to brain structure and function in patients with LADA.

Disruption of brain regional homogeneity and functional connectivity in male NAFLD: evidence from a pilot resting-state fMRI study.

BACKGROUND: The neurophysiological mechanisms underlying cognitive deficits in non-alcoholic fatty liver disease (NAFLD) remain unknown. Cognitive changes may be caused by brain alterations in neural activity and functional connectivity (FC). AIM: This study aims to investigate the alterations between spontaneous brain neural activity and FC in male NAFLD patients and the relationship of neural activity with cognitive performance. METHODS: In this prospective study, 33 male pre-cirrhosis NAFLD subjects and 20 male controls matched for age, education level, and body mass index. All participants underwent resting-state functional magnetic resonance imaging scans and neuropsychological examinations. Regional homogeneity (ReHo) analysis was used to investigate the brain function in NAFLD, and regions with significantly altered ReHo were selected as seeds for subsequent FC analysis. Partial correlation analysis was used to assess the relationships between altered ReHo measures and cognitive performance indicators. RESULTS: Compared with the controls, the NAFLD patients showed increased ReHo in the opercular part of the right inferior frontal gyrus (IFGoperc) and decreased ReHo in the right middle frontal gyrus (MFG) and left superior parietal gyrus (SPG). The subsequent FC analysis showed increased FC between these regions (right IFGoperc, right MFG, and left SPG) and nodes of the default mode network (DMN) (such as left supraMarginal, left median cingulate and paracingulate gyri, left precuneus, orbital part of left medial frontal gyrus, and bilateral posterior cingulate gyrus). In addition, significant positive correlations were observed between NAFLD patients' clock drawing test scores and altered ReHo in prefrontal cortices (right IFGoperc and right MFG). CONCLUSION: Before developing cirrhosis, NAFLD patients showed altered neural activity in several brain regions and altered FC between the salience network and DMN. These alterations could potentially be a compensatory mechanism to maintain cognitive function in pre-cirrhosis NAFLD patients.

Static and dynamic changes of intrinsic brain local connectivity in internet gaming disorder.

BACKGROUND: Studies have revealed that intrinsic neural activity varies over time. However, the temporal variability of brain local connectivity in internet gaming disorder (IGD) remains unknown. The purpose of this study was to explore the alterations of static and dynamic intrinsic brain local connectivity in IGD and whether the changes were associated with clinical characteristics of IGD. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 36 individuals with IGD (IGDs) and 44 healthy controls (HCs) matched for age, gender and years of education. The static regional homogeneity (sReHo) and dynamic ReHo (dReHo) were calculated and compared between two groups to detect the alterations of intrinsic brain local connectivity in IGD. The Internet Addiction Test (IAT) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the severity of online gaming addiction and sleep quality, respectively. Pearson correlation analysis was used to evaluate the relationship between brain regions with altered sReHo and dReHo and IAT and PSQI scores. Receiver operating characteristic (ROC) curve analysis was used to reveal the potential capacity of the sReHo and dReHo metrics to distinguish IGDs from HCs. RESULTS: Compared with HCs, IGDs showed both increased static and dynamic intrinsic local connectivity in bilateral medial superior frontal gyrus (mSFG), superior frontal gyrus (SFG), and supplementary motor area (SMA). Increased dReHo in the left putamen, pallidum, caudate nucleus and bilateral thalamus were also observed. ROC curve analysis showed that the brain regions with altered sReHo and dReHo could distinguish individuals with IGD from HCs. Moreover, the sReHo values in the left mSFG and SMA as well as dReHo values in the left SMA were positively correlated with IAT scores. The dReHo values in the left caudate nucleus were negatively correlated with PSQI scores. CONCLUSIONS: These results showed impaired intrinsic local connectivity in frontostriatothalamic circuitry in individuals with IGD, which may provide new insights into the underlying neuropathological mechanisms of IGD. Besides, dynamic changes of intrinsic local connectivity in caudate nucleus may be a potential neurobiological marker linking IGD and sleep quality.

Altered functional activity in the right superior temporal gyrus in patients with definite vestibular migraine.

BACKGROUND: Vestibular migraine (VM) is one of the most common causes of episodic central vestibular disorders; it is worth investigating whether VM belongs to the migraine subtype or is a separate disorder. The study is aimed at investigating resting-state functional brain activity alterations in patients with definite VM (dVM). METHODS: Seventeen patients with dVM, 8 patients with migraine, and 17 health controls (HCs) were recruited. The amplitude of low frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were calculated to observe the changes in spontaneous brain activity. RESULTS: Compared with HCs, VM patients showed significantly increased ALFF values in the right temporal lobe (P = 0.002) and increased ReHo values in the right superior, middle, and inferior temporal gyrus (STG, MTG, and ITG, P = 0.013); patients with migraine showed significantly increased ALFF values in the right limbic lobe (P = 0.04), left ITG (P = 0.024), and right frontal lobe (P < 0.001), significantly decreased ALFF values in the pons and brainstem (P = 0.013), and significantly decreased ReHo values in the frontal cortex (P < 0.001). Compared with patients with migraine, VM patients showed significantly increased fALFF values in the right parietal lobe (P = 0.011) and right frontal lobe (P = 0.026) and significantly increased ReHo values in the right thalamus (P = 0.043). CONCLUSIONS: Patients with VM and migraine both had altered brain function, but the regions involved are different.

Hemodynamic and metabolic correspondence of resting-state voxel-based physiological metrics in healthy adults.

Voxel-based physiological (VBP) variables derived from blood oxygen level dependent (BOLD) fMRI time-course variations include: amplitude of low frequency fluctuations (ALFF), fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity (ReHo). Although these BOLD-derived variables can detect between-group (e.g. disease vs control) spatial pattern differences, physiological interpretations are not well established. The primary objective of this study was to quantify spatial correspondences between BOLD VBP variables and PET measurements of cerebral metabolic rate and hemodynamics, being well-validated physiological standards. To this end, quantitative, whole-brain PET images of metabolic rate of glucose (MRGlu; 18FDG) and oxygen (MRO2; 15OO), blood flow (BF; H215O) and blood volume (BV; C15O) were obtained in 16 healthy controls. In the same subjects, BOLD time-courses were obtained for computation of ALFF, fALFF and ReHo images. PET variables were compared pair-wise with BOLD variables. In group-averaged, across-region analyses, ALFF corresponded significantly only with BV (R = 0.64; p < 0.0001). fALFF corresponded most strongly with MRGlu (R = 0.79; p < 0.0001), but also significantly (p < 0.0001) with MRO2 (R = 0.68), BF (R = 0.68) and BV (R=0.68). ReHo performed similarly to fALFF, with significant strong correspondence (p < 0.0001) with MRGlu (R = 0.78), MRO2 (R = 0.54), and, but less strongly with BF (R = 0.50) and BV (R=0.50). Mutual information analyses further clarified these physiological interpretations. When conditioned by BV, ALFF retained no significant MRGlu, MRO2 or BF information. When conditioned by MRGlu, fALFF and ReHo retained no significant MRO2, BF or BV information. Of concern, however, the strength of PET-BOLD correspondences varied markedly by brain region, which calls for future investigation on physiological interpretations at a regional and per-subject basis.

Regional Homogeneity Alterations in Patients with Impaired Consciousness. An Observational Resting-State fMRI Study.

PURPOSE: It is always challenging to correctly differentiate between minimally conscious state (MCS) and vegetative state/unresponsive wakefulness syndrome (VS/UWS) among disorders of consciousness (DOC) patients. However, the underlying neural mechanisms of awareness identification remain incompletely understood. METHODS: Using regional homogeneity (ReHo) analysis, we evaluated how regional connectivity of brain regions is disrupted in MCS and VS/UWS patients. Resting-state functional magnetic resonance imaging was conducted in 14 MCS patients, 25 VS/UWS patients, and 30 age-matched healthy individuals. RESULTS: We found that MCS and VS/UWS patients demonstrated DOC-dependent reduced ReHo within widespread brain regions including posterior cingulate cortices (PCC), medial prefrontal cortices (mPFC), and bilateral fronto-parieto-temporal cortices and showed increased ReHo in limbic structures. Moreover, a positive correlation between Coma Recovery Scale-Revised (CRS-R) total scores and reduced ReHo in the left precuneus was observed in VS/UWS patients, despite the linear trend was not found in MCS patients. In addition, ReHo were also observed reduced in three mainly intrinsic connectivity networks (ICNs), including default mode network (DMN), executive control network (ECN), and salience network (SN). Notably, as the clinical symptoms of consciousness disorders worsen from MCS to VS/UWS, ReHo in dorsal DMN, left ECN, and posterior SN became significantly reduced. CONCLUSION: These findings make a further understanding of the underlying neural mechanism of regional connectivity among DOC patients and provide additional neuroimaging-based biomarkers for the clinical diagnosis of MCS and VS/UWS patients.

Spontaneous neural activity changes after bariatric surgery: A resting-state fMRI study.

BACKGROUND: Metabolic disorders associated with obesity could lead to alterations in brain structure and function. Whether these changes can be reversed after weight loss is unclear. Bariatric surgery provides a unique opportunity to address these questions because it induces marked weight loss and metabolic improvements which in turn may impact the brain in a longitudinal fashion. Previous studies found widespread changes in grey matter (GM) and white matter (WM) after bariatric surgery. However, findings regarding changes in spontaneous neural activity following surgery, as assessed with the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity of neural activity (ReHo), are scarce and heterogenous. In this study, we used a longitudinal design to examine the changes in spontaneous neural activity after bariatric surgery (comparing pre- to post-surgery), and to determine whether these changes are related to cardiometabolic variables. METHODS: The study included 57 participants with severe obesity (mean BMI=43.1 ± 4.3 kg/m2) who underwent sleeve gastrectomy (SG), biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB), scanned prior to bariatric surgery and at follow-up visits of 4 months (N = 36), 12 months (N = 29), and 24 months (N = 14) after surgery. We examined fALFF and ReHo measures across 1022 cortical and subcortical regions (based on combined Schaeffer-Xiao parcellations) using a linear mixed effect model. Voxel-based morphometry (VBM) based on T1-weighted images was also used to measure GM density in the same regions. We also used an independent sample from the Human Connectome Project (HCP) to assess regional differences between individuals who had normal-weight (N = 46) or severe obesity (N = 46). RESULTS: We found a global increase in the fALFF signal with greater increase within dorsolateral prefrontal cortex, precuneus, inferior temporal gyrus, and visual cortex. This effect was more significant 4 months after surgery. The increase within dorsolateral prefrontal cortex, temporal gyrus, and visual cortex was more limited after 12 months and only present in the visual cortex after 24 months. These increases in neural activity measured by fALFF were also significantly associated with the increase in GM density following surgery. Furthermore, the increase in neural activity was significantly related to post-surgery weight loss and improvement in cardiometabolic variables, such as blood pressure. In the independent HCP sample, normal-weight participants had higher global and regional fALFF signals, mainly in dorsolateral/medial frontal cortex, precuneus and middle/inferior temporal gyrus compared to the obese participants. These BMI-related differences in fALFF were associated with the increase in fALFF 4 months post-surgery especially in regions involved in control, default mode and dorsal attention networks. CONCLUSIONS: Bariatric surgery-induced weight loss and improvement in metabolic factors are associated with widespread global and regional increases in neural activity, as measured by fALFF signal. These findings alongside the higher fALFF signal in normal-weight participants compared to participants with severe obesity in an independent dataset suggest an early recovery in the neural activity signal level after the surgery.

Brain Activity of Benzoate, a D-Amino Acid Oxidase Inhibitor, in Patients With Mild Cognitive Impairment in a Randomized, Double-Blind, Placebo Controlled Clinical Trial.

BACKGROUND: Current anti-dementia drugs cannot benefit mild cognitive impairment (MCI). Sodium benzoate (a D-amino acid oxidase [DAO] inhibitor) has been found to improve the cognitive function of patients with early-phase Alzheimer's disease (mild Alzheimer's disease or MCI). However, its effect on brain function remains unknown. This study aimed to evaluate the influence of benzoate on functional magnetic resonance imaging in patients with amnestic MCI. METHODS: This was a 24-week, randomized, double-blind, placebo-controlled trial that enrolled 21 patients with amnestic MCI and allocated them randomly to either of 2 treatment groups: (1) benzoate group (250-1500 mg/d), or (2) placebo group. We assessed the patients' working memory, verbal learning and memory, and resting-state functional magnetic resonance imaging and regional homogeneity (ReHo) maps at baseline and endpoint. RESULTS: Resting-state ReHo decreased in right orbitofrontal cortex after benzoate treatment but did not change after placebo. Moreover, after benzoate treatment, the change in working memory was positively correlated with the change in ReHo in right precentral gyrus and right middle occipital gyrus; and the change in verbal learning and memory was positively correlated with the change in ReHo in left precuneus. In contrast, after placebo treatment, the change in working memory or in verbal learning and memory was not correlated with the change in ReHo in any brain region. CONCLUSION: The current study is the first to our knowledge to demonstrate that a DAO inhibitor, sodium benzoate herein, can alter brain activity as well as cognitive functions in individuals with MCI. The preliminary finding lends supports for DAO inhibition as a novel approach for early dementing processes.

Structural and Functional Changes in the Cerebellum and Brainstem in Patients with Benign Paroxysmal Positional Vertigo.

Benign paroxysmal positional vertigo (BPPV) is one of the most common peripheral vestibular diseases. Since the peripheral vestibular system connects with the cerebellum via the brainstem, repeated episodic vertigo may result in progressive structural and functional changes in the cerebellum and brainstem. In the present work, voxel-based morphometry (VBM) of T1-weighted images and resting-state functional magnetic resonance imaging (fMRI) in 32 patients with BPPV and 32 matched healthy controls were used to assess cerebellar and brainstem anatomical and spontaneous resting-state brain activity alterations associated with BPPV. We used a spatially unbiased infratentorial template toolbox in combination with VBM to analyze cerebellar and brainstem gray matter volume (GMV), fractional amplitude of low-frequency fluctuations (fALFF), and regional homogeneity (ReHo). Patients with BPPV showed decreased GMV in the right cerebellum posterior lobe/cerebellar tonsil extending to the cerebellum anterior lobe and pons relative to healthy controls. BPPV patients also exhibited significantly higher fALFF values in the right pons and left pons and higher ReHo values in the left cerebellum posterior lobe/Crus2 than the controls. Furthermore, the fALFF z-scores in the pons were positively correlated with the duration of vertigo at baseline and dizziness visual analog scale scores 1 week after canalith repositioning procedures (CRPs). BPPV patients exhibited structural and functional changes in the cerebellum and pons, which may reflect the adaptation and plasticity of these anatomical structures after repeated attacks of episodic vertigo. These results indicate that the changes in pons function may be closely related to residual dizziness after CRPs.

Altered spontaneous neural activity in the precuneus, middle and superior frontal gyri, and hippocampus in college students with subclinical depression.

BACKGROUND: Subclinical depression (ScD) is a prevalent condition associated with relatively mild depressive states, and it poses a high risk of developing into major depressive disorder (MDD). However, the neural pathology of ScD is still largely unknown. Identifying the spontaneous neural activity involved in ScD may help clarify risk factors for MDD and explore treatment strategies for mild stages of depression. METHODS: A total of 34 ScD subjects and 40 age-, sex-, and education-matched healthy controls were screened from 1105 college students. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of resting-state fMRI were calculated to reveal neural activity. Strict statistical strategies, including Gaussian random field (GRF), false discovery rate (FDR), and permutation test (PT) with threshold-free cluster enhancement (TFCE), were conducted. Based on the altered ALFF and ReHo, resting-state functional connectivity (RSFC) was further analyzed using a seed-based approach. RESULTS: The right precuneus and left middle frontal gyrus (MFG) both showed significantly increased ALFF and ReHo in ScD subjects. Moreover, the left hippocampus and superior frontal gyrus (SFG) showed decreased ALFF and increased ReHo, respectively. In addition, ScD subjects showed increased RSFC between MFG and hippocampus compared to healthy controls, and significant positive correlation was found between the Beck Depression Inventory-II (BDI-II) score and RSFC from MFG to hippocampus in ScD group. CONCLUSION: Spontaneous neural activities in the right precuneus, left MFG, SFG, and hippocampus were altered in ScD subjects. Functional alterations in these dorsolateral prefrontal cortex and default mode network regions are largely related to abnormal emotional processing in ScD, and indicate strong associations with brain impairments in MDD, which provide insight into potential pathophysiology mechanisms of subclinical depression.

Spatial patterns of intrinsic brain activity and functional connectivity in facial synkinesis patients.

OBJECTIVES: As one of the most objectionable sequelae of facial paralysis, patients with facial synkinesis are more likely to be depressed and have lower quality of life than other facial paralysis patients. However, there is no research on the spatial patterns of intrinsic brain activity and functional connectivity in these patients. The objective of this study was to investigate the spatial patterns and cerebral plasticity of facial synkinesis patients. METHODS: A total of 20 facial synkinesis patients (18 men and 2 women; mean age: 33.35 ± 6.97 years old) and 19 healthy controls (17 men and 2 women; mean age: 33.21 ± 6.75 years old) were enrolled in this study. resting-state functional magnetic resonance imaging (rs-fMRI) data were collected, and the amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated for each participant. Two-sample t-tests were performed to compare the ALFF, ReHo, and DC maps between the two groups. RESULTS: Compared with the healthy controls, facial synkinesis patients exhibited decreased ALFF in the fusiform gyrus, lingual gyrus, parahippocampal gyrus, triangular inferior frontal gyrus, precentral gyrus, postcentral gyrus, cingulate gyrus, superior frontal gyrus, precuneus, caudate nucleus and thalamus; decreased ReHo in the cingulate gyrus, superior frontal gyrus, insula, superior temporal gyrus, orbital middle frontal gyrus, caudate nucleus and thalamus; and decreased DC in the frontal lobe, insula, cingulate gyrus, superior temporal gyrus, lenticular putamen, hippocampus and parahippocampal gyrus. We found significant overlap in the superior frontal gyrus across the ALFF, ReHo and DC analyses. CONCLUSIONS: In facial synkinesis patients, the neurological activity in brain areas is reduced and the local synchronization in motion-related brain regions is decreased. The superior frontal gyrus could be a crucial region in the unique spatial patterns of intrinsic brain activity and functional connectivity in these patients.

Regional homogeneity alterations in multi-frequency bands in tension-type headache: a resting-state fMRI study.

OBJECTIVES: In this study, we aimed to investigate the spontaneous neural activity in the conventional frequency band (0.01-0.08 Hz) and two sub-frequency bands (slow-4: 0.027-0.073 Hz, and slow-5: 0.01-0.027 Hz) in tension-type headache (TTH) patients with regional homogeneity (ReHo) analyses. METHODS: Thirty-eight TTH patients and thirty-eight healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (RS-fMRI) scanning to investigate abnormal spontaneous neural activity using ReHo analysis in conventional frequency band (0.01-0.08 Hz) and two sub-frequency bands (slow-4: 0.027-0.073 Hz and slow-5: 0.01-0.027 Hz). RESULTS: In comparison with the HC group, patients with TTH exhibited ReHo increases in the right medial superior frontal gyrus in the conventional frequency band (0.01-0.08 Hz). The between group differences in the slow-5 band (0.01-0.027 Hz) highly resembled the differences in the conventional frequency band (0.01-0.08 Hz); even the voxels with increased ReHo were spatially more extensive, including the right medial superior frontal gyrus and the middle frontal gyrus. In contrast, no region showed significant between-group differences in the slow-4 band (0.027-0.073 Hz). The correlation analyses showed no correlation between the ReHo values in TTH patients and VAS scores, course of disease and number of seizures per month in conventional band (0.01-0.08 Hz), slow-4 band (0.027-0.073 Hz), as well as in slow-5 band (0.01-0.027 Hz). CONCLUSIONS: The results showed that the superior frontal gyrus and middle frontal gyrus were involved in the integration and processing of pain signals. In addition, the abnormal spontaneous neural activity in TTH patients was frequency-specific. Namely, slow-5 band (0.01-0.027 Hz) might contain additional useful information in comparison to slow-4 band (0.027-0.073 Hz). This preliminary exploration might provide an objective imaging basis for the understanding of the pathophysiological mechanism of TTH.

Concurrent brain structural and functional alterations in patients with migraine without aura: an fMRI study.

OBJECTIVES: To explore the possible concurrent brain functional and structural alterations in patients with migraine without aura (MwoA) patients compared to healthy subjects (HS). METHODS: Seventy-two MwoA patients and forty-six HS were recruited. 3D-T1 and resting state fMRI data were collected during the interictal period for MwoA and HS. Voxel-based morphometry (VBM) for structure analysis and regional homogeneity (Reho) for fMRI analysis were applied. The VBM and Reho maps were overlapped to determine a possible brain region with concurrent functional and structural alteration in MwoA patients. Further analysis of resting state functional connectivity (FC) alteration was applied with this brain region as the seed. RESULTS: Compared with HS, MwoA patients showed decreased volume in the bilateral superior and inferior colliculus, periaqueductal gray matter (PAG), locus ceruleus, median raphe nuclei (MRN) and dorsal pons medulla junction. MwoA patients showed decreased Reho values in the middle occipital gyrus and inferior occipital gyrus, and increased Reho values in the MRN. Only a region in the MRN showed both structural and functional alteration in MwoA patients. Pearson correlation analysis showed that there was no association between volume or Reho values of the MRN and headache frequency, headache intensity, disease duration, self-rating anxiety scale or self-rating depression scale in MwoA patients. Resting state functional connectivity (FC) with the MRN as the seed showed that MwoA patients had increased FC between the MRN and PAG. CONCLUSIONS: MRN are involved in the pathophysiology of migraine during the interictal period. This study may help to better understand the migraine symptoms. TRIAL REGISTRATION: NCT01152632 . Registered 27 June 2010.

A study on BOLD fMRI of the brain basic activities of MDD and the first-degree relatives.

Introduction: The present study aims to explore the characteristics and differences of the ReHo, ALFF and fALFF of brain in the resting state of depression and first-degree relatives, in order to identify candidate central prodromal biomarkers of depression.Method: Three groups of medication-free patients (39-59 years old) was involved in this study, including the patients with major depression disorder (MDD group, n = 15), healthy volunteers with first-degree relatives with MDD (first-degree relatives group, n = 15), healthy volunteers with no personal or family history of MDD (the control group [HC], n = 15). Participants underwent functional MRI while staying in a resting state after a conventional MRI scanning on a clinical 3 T system(Siemens Skyra, Germany).Results: The ReHo, ALFF and fALFF values are different in brain of MDD, first-degree relatives, and HC (p<.05). MDD patients exhibited abnormal spontaneous activity in multiple brain regions which are closely related to emotion regulation and perception. The present findings provide further insight into the pathological mechanisms underlying MDD.Conclusion: With the widespread abnormal values of brain in MDD and first-degree relatives measured, we can get a hypothesis that these abnormalities may be associated with cognitive network disorders and emotional distress in MDD.Key pointsThe fMRI could increase the early validity of MDD as a new diagnostic and disease-monitoring tool.Monitoring ReHo, ALFF, fALFF values using fMRI can provide insight into the presence and evolution of MDD disease and permit objective evaluation of brain abnormalities.It appears that ReHo, ALFF, fALFF could be used as markers for monitoring disease progression and treatment effects in MDD patients in the future.

Detecting resting-state brain activity using OEF-weighted imaging.

Traditional resting-state functional magnetic resonance imaging (fMRI) is mainly based on the blood oxygenation level-dependent (BOLD) contrast. The oxygen extraction fraction (OEF) represents an important parameter of brain metabolism and is a key biomarker of tissue viability, detecting the ratio of oxygen utilization to oxygen delivery. Investigating spontaneous fluctuations in the OEF-weighted signal is crucial for understanding the underlying mechanism of brain activity because of the immense energy budget during the resting state. However, due to the poor temporal resolution of OEF mapping, no studies have reported using OEF contrast to assess resting-state brain activity. In this fMRI study, we recorded brain OEF-weighted fluctuations for 10 min in healthy volunteers across two scanning visits, using our recently developed pulse sequence that can acquire whole-brain voxel-wise OEF-weighted signals with a temporal resolution of 3 s. Using both group-independent component analysis and seed-based functional connectivity analysis, we robustly identified intrinsic brain networks, including the medial visual, lateral visual, auditory, default mode and bilateral executive control networks, using OEF contrast. Furthermore, we investigated the resting-state local characteristics of brain activity based on OEF-weighted signals using regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF). We demonstrated that the gray matter regions of the brain, especially those in the default mode network, showed higher ReHo and fALFF values with the OEF contrast. Moreover, voxel-wise test-retest reliability comparisons across the whole brain demonstrated that the reliability of resting-state brain activity based on the OEF contrast was moderate for the network indices and high for the local activity indices, especially for ReHo. Although the reliabilities of the OEF-based indices were generally lower than those based on BOLD, the reliability of OEF-ReHo was slightly higher than that of BOLD-ReHo, with a small effect size, which indicated that OEF-ReHo could be used as a reliable index for characterizing resting-state local brain activity as a complement to BOLD. In conclusion, OEF can be used as an effective contrast to study resting-state brain activity with a medium to high test-retest reliability.

Reproducibility of functional brain alterations in major depressive disorder: Evidence from a multisite resting-state functional MRI study with 1,434 individuals.

Resting-state functional MRI (R-fMRI) studies have demonstrated widespread alterations in brain function in patients with major depressive disorder (MDD). However, a clear and consistent conclusion regarding a repeatable pattern of MDD-relevant alterations is still limited due to the scarcity of large-sample, multisite datasets. Here, we address this issue by including a large R-fMRI dataset with 1434 participants (709 patients with MDD and 725 healthy controls) from five centers in China. Individual functional activity maps that represent very local to long-range connections are computed using the amplitude of low-frequency fluctuations, regional homogeneity and distance-related functional connectivity strength. The reproducibility analyses involve different statistical strategies, global signal regression, across-center consistency, clinical variables, and sample size. We observed significant hypoactivity in the orbitofrontal, sensorimotor, and visual cortices and hyperactivity in the frontoparietal cortices in MDD patients compared to the controls. These alterations are not affected by different statistical analysis strategies, global signal regression and medication status and are generally reproducible across centers. However, these between-group differences are partially influenced by the episode status and the age of disease onset in patients, and the brain-clinical variable relationship exhibits poor cross-center reproducibility. Bootstrap analyses reveal that at least 400 subjects in each group are required to replicate significant alterations (an extent threshold of P < .05 and a height threshold of P < .001) at 50% reproducibility. Together, these results highlight reproducible patterns of functional alterations in MDD and relevant influencing factors, which provides crucial guidance for future neuroimaging studies of this disorder.

Gastric-bypass surgery induced widespread neural plasticity of the obese human brain.

Bariatric surgery has become the gold standard for the treatment of morbid obesity (body mass index (BMI) ≥ 40 kg/m2), but only few studies investigated its plastic influences on the obese brain. In this longitudinal study, we combined structural and functional magnetic resonance brain imaging (MRI) in 27 patients (BMI 47.8 ± 5.5 kg/m2) undergoing gastric-bypass surgery and 14 non-obese matched controls (BMI 24.7 ± 3.4 kg/m2). Over the first year after surgery, patients presented widespread changes in white matter density (WMD) as well as gray matter density (GMD) in the cerebral cortex of all lobes, subcortical structures, the brainstem as well as the cerebellum, but no changes in white matter water diffusivity throughout the brain. Voxel-by-voxel regression analyses revealed that all GMD and WMD changes were well associated with elevated regional homogeneity of spontaneous neural activity (ReHo) in blood-oxygenation level-dependent signals. Spatial-temporal integration of structural and functional MRI suggests that gastric-bypass surgery induces widespread plastic changes in brain structure that concurrently homogenizes the functional profile of the cortex, subcortical regions as well as white matter structures.