Aberrant brain entropy in posttraumatic stress disorder comorbid with major depressive disorder during the coronavirus disease 2019 pandemic.

Aim: Previously, neuroimaging studies on comorbid Posttraumatic-Major depression disorder (PTSD-MDD) comorbidity found abnormalities in multiple brain regions among patients. Recent neuroimaging studies have revealed dynamic nature on human brain activity during resting state, and entropy as an indicator of dynamic regularity may provide a new perspective for studying abnormalities of brain function among PTSD-MDD patients. During the COVID-19 pandemic, there has been a significant increase in the number of patients with PTSD-MDD. We have decided to conduct research on resting-state brain functional activity of patients who developed PTSD-MDD during this period using entropy. Methods: Thirty three patients with PTSD-MDD and 36 matched TCs were recruited. PTSD and depression symptoms were assessed using multiple clinical scales. All subjects underwent functional magnetic resonance imaging (fMRI) scans. And the brain entropy (BEN) maps were calculated using the BEN mapping toolbox. A two-sample t-test was used to compare the differences in the brain entropy between the PTSD-MDD comorbidity group and TC group. Furthermore, correlation analysis was conducted between the BEN changes in patients with PTSD-MDD and clinical scales. Results: Compared to the TCs, PTSD-MDD patients had a reduced BEN in the right middle frontal orbital gyrus (R_MFOG), left putamen, and right inferior frontal gyrus, opercular part (R_IFOG). Furthermore, a higher BEN in the R_MFOG was related to higher CAPS and HAMD-24 scores in the patients with PTSD-MDD. Conclusion: The results showed that the R_MFOG is a potential marker for showing the symptom severity of PTSD-MDD comorbidity. Consequently, PTSD-MDD may have reduced BEN in frontal and basal ganglia regions which are related to emotional dysregulation and cognitive deficits.

Altered functional connectivity strength in chronic insomnia associated with gut microbiota composition and sleep efficiency.

Background: There is limited evidence on the link between gut microbiota (GM) and resting-state brain activity in patients with chronic insomnia (CI). This study aimed to explore the alterations in brain functional connectivity strength (FCS) in CI and the potential associations among altered FCS, GM composition, and neuropsychological performance indicators. Materials and methods: Thirty CI patients and 34 age- and gender-matched healthy controls (HCs) were recruited. Each participant underwent resting-state functional magnetic resonance imaging (rs-fMRI) for the evaluation of brain FCS and was administered sleep-, mood-, and cognitive-related questionnaires for the evaluation of neuropsychological performance. Stool samples of CI patients were collected and subjected to 16S rDNA amplicon sequencing to assess the relative abundance (RA) of GM. Redundancy analysis or canonical correspondence analysis (RDA or CCA, respectively) was used to investigate the relationships between GM composition and neuropsychological performance indicators. Spearman correlation was further performed to analyze the associations among alterations in FCS, GM composition, and neuropsychological performance indicators. Results: The CI group showed a reduction in FCS in the left superior parietal gyrus (SPG) compared to the HC group. The correlation analysis showed that the FCS in the left SPG was correlated with sleep efficiency and some specific bacterial genera. The results of CCA and RDA showed that 38.21% (RDA) and 24.62% (CCA) of the GM composition variation could be interpreted by neuropsychological performance indicators. Furthermore, we found complex relationships between Alloprevotella, specific members of the family Lachnospiraceae, Faecalicoccus, and the FCS alteration, and neuropsychological performance indicators. Conclusion: The brain FCS alteration of patients with CI was related to their GM composition and neuropsychological performance indicators, and there was also an association to some extent between the latter two, suggesting a specific interaction pattern among the three aspects: brain FCS alteration, GM composition, and neuropsychological performance indicators.

Altered cerebral blood flow patterns in ankylosing spondylitis: A three-dimensional pseudo-continuous arterial spin labeling study.

Objective: This study aimed to detect the cerebral blood flow (CBF) values changes in patients with ankylosing spondylitis (AS) and to evaluate the correlation between the CBF values and the specific clinical characteristics. Materials and methods: Forty-eight patients with AS (43 male and 5 female) and 42 healthy controls (HCs) (38 male and 4 female) were recruited. Three-dimensional pseudo-continuous arterial spin labeling (3D-pCASL) was performed on a 3.0T magnetic resonance imaging (MRI). CBF values were obtained on the Philips post-processing workstation based on arterial spin labeling (ASL) data. The two-sample t-test was used to compare CBF differences. The correlation between CBF values and specific clinical characteristics of AS was evaluated. Results: The AS group showed increased CBF values in the right precentral gyrus, the left inferior frontal gyrus, and the left temporal pole compared with HCs the AS group also showed decreased CBF values in the left precuneus and the left superior occipital gyrus compared with HCs. There were no significant correlations between the CBF values and the clinical characteristics including total back pain (TBP), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Conclusion: Patients with AS displayed CBF changes compared with HCs using 3D-PCASL. These results may enhance our understanding of the neural substrates of AS and provide evidence of AS-related neurological impairment.

Abnormal Cerebral Blood Flow and Volumetric Brain Morphometry in Patients With Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is a serious breathing disorder, leading to myocardial infarction, high blood pressure, and stroke. Brain morphological changes have been widely reported in patients with OSA. The pathophysiological mechanisms of cerebral blood flow (CBF) changes associated with OSA are not clear. In this study, 20 patients with OSA and 36 healthy controls (HCs) were recruited, and then pseudo-continuous arterial spin labeling (pCASL) and voxel-based morphometry (VBM) methods were utilized to explore blood perfusion and morphological changes in the patients with OSA. Compared with the HC group, the OSA group showed increased CBF values in the right medial prefrontal cortex (mPFC), left precentral gyrus, and right insula and showed decreased CBF values in the right temporal pole (TP) and the right cerebellum_Crus2. Compared with the HC group, the patients with OSA showed decreased gray matter volume (GMV) in the right dorsal lateral prefrontal cortex (DLPFC), the right occipital pole, and the vermis. There were no significantly increased GMV brain regions found in patients with OSA. Pearson correlation analysis showed that the reduced GMV in the right DLPFC and the right occipital pole was both positively correlated with Mini-Mental State Examination (MMSE) (r = 0.755, p < 0.001; r = 0.686, p = 0.002) and Montreal Cognitive Assessment (MoCA) scores (r = 0.716, p = 0.001; r = 0.601, p = 0.008), and the reduced GMV in the right occipital pole was negatively correlated with duration of illness (r = -0.497, p = 0.036). Patients with OSA have abnormal blood perfusion metabolism and morphological changes in brain regions including the frontal lobe and the cerebellum and were closely related to abnormal behavior, psychology, and cognitive function, which play an important role in the pathophysiological mechanism of OSA.

Alterations of Regional Homogeneity in Preschool Boys With Autism Spectrum Disorders.

OBJECTIVES: The study was aimed at investigating the alterations of local spontaneous brain activity in preschool boys with autism spectrum disorders (ASD). METHODS: Based on regional homogeneity (ReHo), the acquired resting state functional magnetic resonance imaging (fMRI) data sets, which included 86 boys with ASD and 54 typically developing (TD) boys, were used to detect regional brain activity. Pearson correlation analysis was used to study the relationship between abnormal ReHo value and the Childhood Autism Rating Scale (CARS), Autism Behavior Checklist (ABC), developmental quotient, and age. RESULTS: In the ASD group, we found increased ReHo in the right calcarine as well as decreased ReHo in the opercular part of the left inferior frontal gyrus, the left middle temporal gyrus, the left angular gyrus, and the right medial orbital frontal cortex (p < 0.05, false discovery rate correction). We did not find a correlation between the results of brain regions and the CARS, ABC, and age. CONCLUSIONS: Our study found spontaneous activity changes in multiple brain regions, especially the visual and language-related areas of ASD, that may help to further understand the clinical characteristics of boys with ASD.

Altered Spontaneous Brain Activity and Functional Integration in Hemodialysis Patients With End-Stage Renal Disease.

PURPOSE: Using the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) algorithm to study the alteration of brain function in hemodialysis patients with end-stage renal disease (ESRD). PATIENTS AND METHODS: We recruited 20 patients with ESRD on regular hemodialysis and 17 healthy controls (HCs). All of the participants underwent resting-state fMRI (rs-fMRI), neuropsychological tests, and blood biochemical examination. The individual ALFF values between the two groups were tested by an independent sample t-test. Then, we set the altered ALFF brain areas as seed regions of interest (ROIs), and FC analysis was used to investigate the functional integration patterns between the seed ROI and the voxels within the whole brain. RESULTS: The ALFF values of the right precuneus and angular gyrus (RAG) in the ESRD group were lower than those in the HC subjects, but the right precentral gyrus showed higher ALFF values in patients. Hemoglobin (Hb) was negatively correlated with the ALFF values of the right precentral gyrus, and the ALFF values of the right precuneus were negatively correlated with line-tracing test (LTT) scores in patients with ESRD. Patients with ESRD show decreased connectivity between the RAG and the left precuneus, right superior frontal gyrus (RSFG), and the connectivity within the RAG was weak. In addition, FC in the RAG-right cuneus, right precuneus-left supramarginal gyrus was enhanced in the patient group. CONCLUSION: Our research suggested that, in hemodialysis patients with ESRD, the brain areas with abnormal spontaneous brain activity and FC are mainly located in the default mode network (DMN) regions. Hb and the LTT results were correlated with abnormal spontaneous brain activity. These findings provide additional evidence to understand the possible underlying neuropathological mechanisms in patients with ESRD.

Increased Left Putamen Volume Correlates With Pain in Ankylosing Spondylitis Patients.

Ankylosing spondylitis (AS) mainly affects the axial skeleton and is an important factor leading to chronic lower back pain in young individuals. However, few studies have explored alterations of brain gray matter volume in AS patients. The purpose of the present study was to describe brain gray matter abnormalities associated with AS pain. A total of 61 AS patients and 52 healthy controls (HCs) were included in this study. Using voxel-based morphometrics, we detected abnormal gray matter volume in AS patients. Based on the voxel-wise analysis, the gray matter volume in the left putamen of the AS group was increased significantly compared with that of the HC group. In addition, we found that the gray matter volume of the left putamen was positively correlated with the duration of AS and total back pain scores, whereas it was not significantly correlated with Bath Ankylosing Spondylitis Disease Activity Index scores, C-reactive protein, or erythrocyte sedimentation rate in AS patients. Taken together, our findings improve our understanding of the neural substrates of pain in AS and provide evidence of AS-related neurological impairment. Hence, further investigation of the pathophysiology of the left putamen in AS is warranted.

Increased Dynamic Amplitude of Low Frequency Fluctuation in Primary Insomnia.

The physiological mechanism underlying primary insomnia (PI) is poorly understood. Resting-state functional magnetic resonance imaging (fMRI) has emerged as a powerful tool to explore PI. However, previous studies ignore the dynamics of the brain activity. In the current study, we aimed to explore altered dynamic intrinsic brain activity in PI. Fifty-nine patients with PI and 47 matched healthy controls (HCs) were recruited and underwent resting-state fMRI. The variance of dynamic amplitude of low frequency fluctuation (dALFF) maps across time was calculated to measure the temporal variability of intrinsic brain activity and then compared between patients with PI and HCs. As a result, patients with PI presented increased variance of dALFF in the bilateral hippocampus extending to the parahippocampus, the right putamen and the right anterior insula cortex. In addition, the variance of dALFF in the right putamen was positively correlated with Self-rating Anxiety Scale (SAS) score in PI. Our results revealed increased instability of intrinsic activity in PI.

Abnormal Rich Club Organization of Structural Network as a Neuroimaging Feature in Relation With the Severity of Primary Insomnia.

PURPOSE: Insomnia is the most prevalent sleep complaint in the general population but is often intractable due to uncertainty regarding the underlying pathomechanisms. Sleep is regulated by a network of neural structures interconnected with the core nodes of the brain connectome referred to as the "rich club". We examined alterations in brain rich-club organization as revealed by diffusion tensor imaging (DTI) and the statistical relationships between abnormalities in rich-club metrics and the clinical features of primary insomnia (PI). METHODS: This study recruited 43 primary insomnia (PI) patients and 42 age-, sex-, and education level-matched healthy controls (HCs). Differences in global and regional network parameters between PI and healthy control groups were compared by nonparametric tests, and Spearman's correlations were calculated to assess associations of these network metrics with PI-related clinical features, including disease duration and scores on the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Self-Rating Anxiety Scale, and Self-Rating Depression Scale. RESULTS: Weighted white matter networks exhibited weaker rich-club organization in PI patients than HCs across different thresholds (50%, 75%, and 90%) and parcellation schemes [automated anatomical labeling (AAL)-90 and AAL-1024]. Aberrant rich-club organization was found mainly in limbic-cortical-basal ganglia circuits and the default-mode network. CONCLUSIONS: Abnormal rich-club metrics are a characteristic feature of PI-related to disease severity. These metrics provide potential clues to PI pathogenesis and may be useful as diagnostic markers and for assessment of treatment response.

Multivariate Pattern Classification of Primary Insomnia Using Three Types of Functional Connectivity Features.

Objective: To explore whether or not functional connectivity (FC) could be used as a potential biomarker for classification of primary insomnia (PI) at the individual level by using multivariate pattern analysis (MVPA). Methods: Thirty-eight drug-naive patients with PI, and 44 healthy controls (HC) underwent resting-state functional MR imaging. Voxel-wise functional connectivity strength (FCS), large-scale functional connectivity (large-scale FC) and regional homogeneity (ReHo) were calculated for each participant. We used support vector machine (SVM) with the three types of metrics as features separately to classify patients from healthy controls. Then we evaluated its classification performances. Finally, FC metrics with significant high classification performance were compared between the two groups and were correlated with clinical characteristics, i.e., Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI), Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS) in the patients' group. Results: The best classifier could reach up to an accuracy of 81.5%, with a sensitivity of 84.9%, specificity of 79.1%, and area under the receiver operating characteristic curve (AUC) of 83.0% (all P < 0.001). Right anterior insular cortex (BA48), left precuneus (BA7), and left middle frontal gyrus (BA8) showed high classification weights. In addition, the right anterior insular cortex (BA48) and left middle frontal gyrus (BA8) were the overlapping regions between MVPA and group comparison. Correlation analysis showed that FCS in left middle frontal gyrus and head of right caudate nucleus were correlated with PSQI and SDS, respectively. Conclusion: The current study suggests abnormal FCS in right anterior insular cortex (BA48) and left middle frontal gyrus (BA8) might serve as a potential neuromarkers for PI.

Aberrant regional homogeneity in post-traumatic stress disorder after traffic accident: A resting-state functional MRI study.

OBJECTIVES: The present study explored the changes in spontaneous regional activity in post-traumatic stress disorder (PTSD) patients, who experienced severe traffic accidents. METHODS: 20 drug-naive PTSD patients and 18 healthy control subjects were imaged using resting-state functional magnetic resonance imaging (rs-fMRI) and analyzed by the algorithm of regional homogeneity (ReHo). RESULTS: Compared to the healthy control group, the PTSD group showed decreased ReHo values in the right angular gyrus. In addition, a negative correlation was found between the activity level of the angular gyrus and the CAPS score. CONCLUSION: The dysfunctions were found in the memory- and emotion-related areas, suggested a possible mechanism of memory dysregulation that might be related to the intrusive memory symptoms of PTSD. These results provided imaging evidence that might provide an in-depth understanding of the intrinsic functional architecture of PTSD.

Cortical morphology of chronic users of codeine-containing cough syrups: association with sulcal depth, gyrification, and cortical thickness.

OBJECTIVES: The study aimed to explore the effects of codeine-containing cough syrup (CCS) exposure on cortical morphology and the relationship between cortical characteristics and CCS dependence. METHODS: Cortical morphometry based on Computational Anatomy Toolbox (CAT12) was used to compare changes in sulcal depth, gyrification, and cortical thickness of the cerebral cortex from 40 CCS users and 40 healthy controls (HCs) with two-sample t tests (p < 0.05, multiple comparison corrected). Relationships between abnormal cortical morphological changes and the duration of CCS use, impulsivity traits, and age of first use were investigated with correlation analysis (p < 0.05, uncorrected). RESULTS: CCS users exhibited significantly increased sulcal depth in the bilateral insula, bilateral lingual, bilateral superior frontal, right precuneus, and right middle frontal regions; increased gyrification in the right precentral cortex; and increased cortical thickness in the bilateral precentral, bilateral precuneus, and right superior temporal cortices compared to HCs. In addition, we found significant correlations between the bilateral insula, right superior frontal cortex, and right precentral gyrus and Barratt Impulsiveness Scale (BIS) total scores. CONCLUSIONS: Chronic CCS abuse may be associated with aberrant sulcal depth, gyrification, and cortical thickness. These morphological changes might serve as an underlying neurobiological mechanism of impulsive behavior in the CCS users. KEY POINTS: • Cortical morphological changes were detected in CCS users. • Increased sulcal depth, gyrification, and cortical thickness of some regions were found in the CCS users. • Positive correlations between cortical morphological changes and BIS total scores were identified.

Altered Local and Large-Scale Dynamic Functional Connectivity Variability in Posttraumatic Stress Disorder: A Resting-State fMRI Study.

Posttraumatic stress disorder (PTSD) is a psychiatric condition that can emerge after exposure to an exceedingly traumatic event. Previous neuroimaging studies have indicated that PTSD is characterized by aberrant resting-state functional connectivity (FC). However, few existing studies on PTSD have examined dynamic changes in resting-state FC related to network formation, interaction, and dissolution over time. In this study, we compared the dynamic resting-state local and large-scale FC between PTSD patients (n = 22) and healthy controls (HC; n = 22; conducted as standard deviation in resting-state local and large-scale FC over a series of sliding windows). Local dynamic FC was examined by calculating the dynamic regional homogeneity (dReHo), and large-scale dynamic FC (dFC) was investigated between regions with significant dReHo group differences. For the PTSD patients, we also investigated the relationship between symptom severity and dFC/dReHo. Our results showed that PTSD patients were characterized by I) increased dynamic (more variable) dReHo in left precuneus (PCu); II) increased dynamic (more variable) dFC between the left PCu and left insula; and III) decreased dFC between left PCu and left inferior parietal lobe (IPL), and decreased dFC between left PCu and right PCu. However, there is no significant correlation between the clinical indicators and dReHo/dFC after the family-wise-error (FWE) correction. These findings provided the initial evidence that PTSD is characterized by aberrant patterns of fluctuating communication within brain system such as the default mode network (DMN) and among different brain systems such as the salience network and the DMN.

Abnormal Topology of the Structural Connectome in the Limbic Cortico-Basal-Ganglia Circuit and Default-Mode Network Among Primary Insomnia Patients.

Purpose: Primary insomnia (PI) is the second most common mental disorder. However, the topologic alterations in structural brain connectome in patients with PI remain largely unknown. Methods: A total of 44 PI patients and 46 age-, gender-, and education level matched healthy control (HC) participants were recruited in this study. Diffusion tensor imaging (DTI) and resting state MRI were used to construct structural connectome for each participant, and the network parameters were employed by non-parametric permutations to evaluate the significant differences between the two groups. Relationships between abnormal network metrics and clinical characteristics, including the disease duration, the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS), were investigated with Spearman's correlation analysis in PI patients. Results: PI patients demonstrated small-world architecture with lower global (P = 0.005) and local (P = 0.035) efficiencies compared with the HC group. The unique hub nodal properties in PI patients were mainly in the right limbic cortico-basal-ganglia circuit. Five disrupted subnetworks in PI patients were observed in the limbic cortico-basal-ganglia circuit and left default-mode networks (DMN) (P < 0.05, NBS corrected). Moreover, most unique hub nodal properties in the right limbic cortico-basal-ganglia circuit were significantly correlated with disease duration, and clinical characteristics (SAS, SDS, ISI scores) in PI processing. Conclusion: These findings suggested the abnormal anatomical network architecture may be closely linked to clinical characteristics in PI. The study provided novel insights into the neural substrates underlying symptoms and neurophysiologic mechanisms of PI.

Abnormal degree centrality in chronic users of codeine-containing cough syrups: A resting-state functional magnetic resonance imaging study.

Codeine-containing cough syrups (CCS) have become one of the most popular drugs of abuse in young population worldwide. However, the neurobiological mechanisms underlying CCS-dependence are yet ill-defined. Therefore, understanding the brain abnormalities in chronic users of CCS is crucial for developing effective interventions. The present study depicted the intrinsic dysconnectivity pattern of whole-brain functional networks at the voxel level in chronic users of CCS. In addition, the degree centrality (DC) changes were correlated to the Barratt Impulsiveness Scale (BIS-11) total score, dose, duration of CCS use, and the age at first use of cough syrups. The current study included 38 chronic CCS users and 34 matched control subjects. All patients were evaluated using the BIS-11. Next, resting-state functional magnetic resonance imaging (rs-fMRI) datasets were acquired from these CCS users and controls. Whole-brain connectivity was analyzed using a graph theory approach: degree centrality (DC). CCS-dependent individuals exhibited low DC values in the left inferior parietal lobule and the left middle temporal gyrus, while high DC values were noted in the right pallidum and the right hippocampus (P < 0.01, AlphaSim corrected). Also, significant correlations were established between average DC value in the left inferior parietal lobule and attentional impulsivity scores and the age at first CCS use. The rs-fMRI study suggested that the abnormal intrinsic dysconnectivity pattern of whole-brain functional networks may provide an insight into the neural substrates of abnormalities in the cognitive control circuit, the reward circuit, and the learning and memory circuit in CCS-dependent individuals.

Aberrant Effective Connectivity of the Right Anterior Insula in Primary Insomnia.

OBJECTIVE: Daytime cognitive impairment is an essential symptom of primary insomnia (PI). However, the underlying neural substrate remains largely unknown. Many studies have shown that the right anterior insula (rAI) as a key node of salience network (SN) plays a critical role in switching between the executive control network (ECN) and the default mode network (DMN) for better performance of cognitively demanding tasks. Aberrant effective connectivity (directional functional connectivity) of rAI with ECN or DMN may be one reason for daytime cognitive impairment in PI patients. Up to now, no effective connectivity study has been conducted on patients with PI during resting state. Our aim is to investigate the effective connectivity between the rAI and the other voxels in the whole brain in PI. MATERIALS AND METHODS: Fifty drug-naive patients with PI and forty age- and sex-matched healthy controls were scanned using resting-state functional MRI. Seed-based Granger causality analysis was used to examine effective connectivity between the rAI, including ventral and dorsal part, and the whole brain. The effective connectivity was compared between the two groups and was correlated with clinical characteristics. RESULTS: Compared with controls, patients showed decreased effective connectivity from the rAI to the bilateral precuneus, the left postcentral gyrus (extending to bilateral precuneus) and the bilateral cerebellum posterior lobe, and decreased effective connectivity from the bilateral orbitofrontal cortex (OFC) to the rAI (single voxel P < 0.001, AlphaSim corrected with P < 0.01). In addition, effective connectivity from the ventral rAI to the left postcentral gyrus and from the left OFC to the ventral rAI were significantly negatively correlated with Insomnia Severity Index scores (r = -0.28/P = 0.046 and r = -0.29/P = 0.038, respectively). CONCLUSION: The present study is the first to reveal aberrant effective connectivity between the SN hub (rAI) and the posterior DMN hub (precuneus) as well as decision-making region (OFC) and sensori-motor region in PI. These findings suggest an aberrant salience processing system of the rAI in PI patients.