Individual differences of white matter characteristic along the anterior insula-based fiber tract circuit for pain empathy in healthy women and women with primary dysmenorrhea.

Pain empathy, defined as the ability of one person to understand another person's pain, shows large individual variations. The anterior insula is the core region of the pain empathy network. However, the relationship between white matter (WM) properties of the fiber tracts connecting the anterior insula with other cortical regions and an individual's ability to modulate pain empathy remains largely unclear. In this study, we outline an automatic seed-based fiber streamline (sFS) analysis method and multivariate pattern analysis (MVPA) to predict the levels of pain empathy in healthy women and women with primary dysmenorrhoea (PDM). Using the sFS method, the anterior insula-based fiber tract network was divided into five fiber cluster groups. In healthy women, interindividual differences in pain empathy were predicted only by the WM properties of the five fiber cluster groups, suggesting that interindividual differences in pain empathy may rely on the connectivity of the anterior insula-based fiber tract network. In women with PDM, pain empathy could be predicted by a single cluster group. The mean WM properties along the anterior insular-rostroventral area of the inferior parietal lobule further mediated the effect of pain on empathy in patients with PDM. Our results suggest that chronic periodic pain may lead to maladaptive plastic changes, which could further impair empathy by making women with PDM feel more pain when they see other people experiencing pain. Our study also addresses an important gap in the analysis of the microstructural characteristics of seed-based fiber tract network.

Reversal of neurovascular decoupling and cognitive impairment in patients with end-stage renal disease during a hemodialysis session: Evidence from a comprehensive fMRI analysis.

Neurovascular (NV) decoupling is a potential neuropathologic mechanism of cognitive impairment in patients with end-stage renal disease (ESRD). Hemodialysis improves cognitive impairment at 24 h post-dialysis, which suggests a potential neuroprotective effect of hemodialysis treatment on the brain. We investigated the effects of hemodialysis treatment on the reversal of NV decoupling associated with cognitive improvement. A total of 39 patients with ESRD and 39 healthy controls were enrolled. All patients were imaged twice during a dialysis session: before hemodialysis (T1pre-dialysis ) and at 24 h after dialysis (T2post-dialysis ). The healthy controls were imaged once. NV coupling was characterized based on correlation coefficients between four types of blood oxygen level-dependent signals and cerebral blood flow (CBF). A battery of neuropsychological and blood tests was performed before the imaging. Patients with ESRD showed improvements in memory and executive function at T2post-dialysis compared with that at T1pre-dialysis . At both T1pre-dialysis and T2post-dialysis , patients with ESRD had lower amplitude of low-frequency fluctuation (ALFF)-CBF coupling than healthy controls. Additionally, patients with ESRD had higher ALFF-CBF coupling at T2post-dialysis than at T1pre-dialysis . Higher memory scores, higher hemoglobin level, lower total plasma homocysteine level, lower systolic blood pressure variance, and lower ultrafiltration volume were associated with higher ALFF-CBF coupling in patients with ESRD after a hemodialysis session. These findings indicate that partial correction of anemia and hyperhomocysteinemia, stable systolic blood pressure, and fluid restriction may be closely linked to the reversal of NV decoupling and improvement in cognition in patients with ESRD.

Abnormal grey matter structural changes in patients with end-stage kidney disease and mild cognitive impairment: correlations with clinical features.

End-stage kidney disease and mild cognitive impairment (ESKD-MCI) affect the quality of life and long-term treatment outcomes of patients affected by these diseases. Clarifying the morphological changes from brain injuries in ESKD-MCI and their relationship with clinical features is helpful for the early identification and intervention of MCI before it progresses to irreversible dementia. This study gathered data from 23 patients with ESKD-MCI, 24 patients with ESKD and non-cognitive impairment (NCI), and 27 health controls (HCs). Structural magnetic resonance studies, cognitive assessments, and general clinical data were collected from all participants. Voxel-based morphometry analysis was performed to compare grey matter (GM) volume differences between the groups. The patients' GM maps and clinical features were subjected to univariate regression to check for possible correlations. Patients with ESKD-MCI displayed significantly more impairments in multiple cognitive domains, including global cognition, visuospatial and executive function, and memory, compared to patients with ESKD-NCI. Using a more liberal threshold (P < 0.001, uncorrected), we found that compared to patients with ESKD-NCI, patients with ESKD-MCI exhibited clusters of regions with lower GM volumes, including the right hippocampus (HIP), parahippocampal gyrus (PHG), Rolandic operculum, and supramarginal gyrus. The volumes of the right HIP and PHG were negatively correlated with serum calcium levels. ESKD-MCI was associated with a subtle volume reduction of GM in several brain areas known to be involved in memory, language, and auditory information processing. We speculate that these slight morphometric impairments may be associated with disturbed calcium metabolism.

Effects of repeated menstrual pain on empathic neural responses in women with primary dysmenorrhea across the menstrual cycle.

Primary dysmenorrhea (PDM) is cyclic menstrual pain in the absence of pelvic anomalies, and it is thought to be a sex-hormone related disorder. Existing study has focused on the effects of menstrual cramps on brain function and structure, ignoring the psychological changes associated with menstrual pain. Here we examined whether pain empathy in PDM differs from healthy controls (HC) using task-based functional magnetic resonance imaging (fMRI). Fifty-seven PDM women and 53 matched HC were recruited, and data were collected at the luteal and menstruation phases, respectively. During fMRI scans, participants viewed pictures displaying exposure to painful situations and pictures without any pain cues and assessed the level of pain experienced by the person in the picture. Regarding the main effect of the pain pictures, our results showed that compared to viewing neutral pictures, viewing pain pictures caused significantly higher activation in the anterior insula (AI), anterior cingulate cortex, and the left inferior parietal lobule; and only the right AI exhibited a significant interaction effect (group × picture). Post-hoc analyses confirmed that, relative to neutral pictures, the right AI failed to be activated in PDM women viewing painsss pictures. Additionally, there was no significant interaction effect between the luteal and menstruation phases. It suggests that intermittent pain can lead to abnormal empathy in PDM women, which does not vary with the pain or pain-free phase. Our study may deepen the understanding of the relationship between recurrent spontaneous pain and empathy in a clinical disorder characterized by cyclic episodes of pain.

[Quantitative analysis methods of white matter microstructure based on diffusion tensor imaging and its application in chronic pain research].

As the two essential components, the white matter and gray matter compose the central nervous system of the brain. Widely known that axons of neurons mainly form the white matter, and these formed nerve fibers are responsible for transmitting information among various brain regions to achieve the coordinated operation of the entire brain. Early research on the white matter could only be done by dissecting living animals or human cadavers, until Basser et al. proposed diffusion tensor imaging (DTI) technology in 1994, which could detect the diffusion characteristics of water in the brain in vivo noninvasively. Accordingly, this technology could be applied to investigate the diffusion movement of water in white matter to obtain the information of direction and micro-anatomy of white matter fiber bundles. With the advancement on the display and analysis of the anatomical structure of white matter fiber bundles, the exploration of microscopic pathological changes, and the assistance of clinical diagnosis and neurophysiological research, DTI technology has become one of the most popular topics in brain science research. Chronic pain refers to pain lasting more than three months, which not only seriously affects the patient's physical and social functions, but also dramatically reduces the quality of life. It was reported that long-term pain stimulation might cause pathological remodeling of the central nervous system, and abnormalities in white matter were found in imaging examinations of patients with chronic pain. This review introduces the quantitative analysis methods of white matter fiber bundle microstructure based on DTI and its application in chronic pain, and further discusses the application value of DTI technology on clinical research of chronic pain.

Neuroimaging features of whole-brain functional connectivity predict attack frequency of migraine.

Migraine is a chronic neurological disorder characterized by attacks of moderate or severe headache accompanying functionally and structurally maladaptive changes in brain. As the headache days/month is often measured by patient self-report and tends to be overestimated than actually experienced, the possibility of using neuroimaging data to predict migraine attack frequency is of great interest. To identify neuroimaging features that could objectively evaluate patients' headache days, a total of 179 migraineurs were recruited from two data center with one dataset used as the training/test cohort and the other used as the validating cohort. The guidelines for controlled trials of prophylactic treatment of chronic migraine in adults were used to identify the frequency of attacks and migraineurs were divided into low (MOl) and high (MOh) subgroups. Whole-brain functional connectivity was used to build multivariate logistic regression models with model iteration optimization to identify MOl and MOh. The best model accurately discriminated MOh from MOl with AUC of 0.91 (95%CI [0.86, 0.95]) in the training/test cohort and 0.79 in the validating cohort. The discriminative features were mainly located within the limbic lobe, frontal lobe, and temporal lobe. Permutation tests analysis demonstrated that the classification performance of these features was significantly better than chance. Furthermore, the indicator of functional connectivity had a higher odds ratio than behavioral variables with implementing a holistic regression analysis. The current findings suggested that the migraine attack frequency could be distinguished by using machine-learning algorithms, and highlighted the role of brain functional connectivity in revealing underlying migraine-related neurobiology.

Abnormal rich club organization in end-stage renal disease patients before dialysis initiation and undergoing maintenance hemodialysis.

BACKGROUND: End-stage renal disease (ESRD) patients are at a substantially higher risk for developing cognitive impairment compared with the healthy population. Dialysis is an essential way to maintain the life of ESRD patients. Based on previous research, there isn't an uncontested result whether cognition was improved or worsened during dialysis. METHODS: To explore the impact of dialysis treatment on cognitive performance, we recruited healthy controls (HCs), predialysis ESRD patients (predialysis group), and maintenance hemodialysis ESRD patients (HD group). All ESRD patients performed six blood biochemistry tests (hemoglobin, urea, cystatin C, Na+, K+, and parathyroid hormone). Neuropsychological tests were used to measure cognitive function. By using diffusion tensor imaging and graph-theory approaches, the topological organization of the whole-brain structural network was investigated. Generalized linear models (GLMs) were performed to investigate blood biochemistry predictors of the neuropsychological tests and the results of graph analyses in the HD group and predialysis group. RESULTS: Neuropsychological analysis showed the HD group exhibited better cognitive function than the predialysis group, but both were worse than HCs. Whole-brain graph analyses revealed that increased global efficiency and normalized shortest path length remained in the predialysis group and HD group than the HCs. Besides, a lower normalized clustering coefficient was found in the predialysis group relative to the HCs and HD group. For the GLM analysis, only the Cystatin C level was significantly associated with the average fiber length of rich club connections in the predialysis group. CONCLUSIONS: Our study revealed that dialysis had a limited effect on cognitive improvement.

White matter tract microstructure of the mPFC-amygdala predicts interindividual differences in placebo response related to treatment in migraine patients.

To investigate whether interindividual variability of white matter (WM) tract microstructure of the medial prefrontal cortex (mPFC)-amygdala circuit could predict 8-week placebo treatment outcomes in patients with migraine without aura (MO) using diffusion tensor imaging (DTI) with a tractography atlas-based analysis algorithm and a linear support vector machine algorithm. This study received institutional review board approval, and all subjects gave informed consent. One hundred and twenty-four MO had an 8-week sham acupuncture treatment. Patients were subdivided into recovering (MOr, >50% improvement in migraine attack frequency after treatment) and persisting (MOp, <50% reduction in number of migraine days). Neuroimaging was collected via magnetic resonance imaging (MRI) in all subjects. Patients were imaged during the interictal phase of migraine (at least 72 hr after, and not within 24 hr of a migraine) before the treatment. WM microstructures were quantified along the selected fiber pathway and were used to evaluate the discrimination performance for classifying MOr and MOp. The combined features of diffusion measures from vertices along the pathways of the mPFC-amygdala accurately discriminated MOr from MOp migraineurs with an accuracy of 84.0% (p < .005, permutation test). The most discriminative WM features that contributed to the classification were located in the external capsule and ACC/mPFC. Our findings suggested that the variability of placebo treatment outcomes in migraineurs could be predicted from priori diffusion measures along the fiber pathways of the mPFC-amygdala, which may demonstrate a potential of WM neuroimaging features as imaging markers for identifying placebo responders in migraine patients.

Altered white matter microstructure mediates the relationship between hemoglobin levels and cognitive control deficits in end-stage renal disease patients.

The brain-kidney crosstalk theory suggested that the brain and kidneys may be considered end organs on parallel trajectories and subject to shared risk factors, which are receiving increasing attention. Cognitive control deficits were frequently presented in patients with end-stage renal disease (ESRD). Whether or not cognitive control impairment is concerned with brain-kidney crosstalk is in need of further research. To detect the relationship between ESRD and cognitive control impairment, diffusion tensor imaging was collected in 64 healthy controls (HCs) and 64 patients with ESRD. Tract-based spatial statistics and fixel-based analysis were used to detect the difference of white matter (WM) microstructure and morphology between ESRD patients and HCs in the whole brain. Tractography atlas-based analysis was also used to investigate the difference of diffusional characteristics along fiber bundles of interest between the two groups. For the whole-brain analysis, ESRD patients showed WM microstructural alteration and fiber density variation in the cingulum. In addition, ESRD patients exhibited higher MD and RD than HCs along the anterior cingulum. Among all of the blood biochemistry tests that represent kidney disease to a degree, the stepwise regression analysis showed that only hemoglobin significantly contributed to the cognitive control deficits in ESRD patients. Mediation analysis proved that the relationship between hemoglobin and cognitive control deficits of ESRD patients was mediated by WM microstructural alteration of the cingulum. Our results indicated that the anterior cingulum was correlated with cognitive control deficits and mediated the impact of hemoglobin on cognitive control.

Altered amygdala-related structural covariance and resting-state functional connectivity in end-stage renal disease patients.

Depression and cognitive control deficits were frequently reported in concurrent end-stage renal disease (ESRD) patients. Neuroimaging studies indicated depression could be a risk factor for cognitive control deficits, and amygdala-related circuitry may play a critical role in this abnormal interaction. To investigate the potential relationship between depressive symptoms and cognitive control reduction in ESRD patients, T1-weighted and resting fMRI images were obtained in 29 ESRD patients and 29 healthy controls. Voxel-based morphometry (VBM), structural covariance (SC) analysis based on grey matter volume (GMV), and functional connectivity (FC) analysis were adopted. All subjects performed the Beck Depression Inventory (BDI) assessment and Stroop test. The patients also underwent blood biochemistry tests (urea, creatinine, phosphate, Ca2+, hematocrit, cystatin, hemoglobin). Compared with controls, GMV reductions were found mainly in the anterior cingulate cortex (ACC) and bilateral amygdala, and decreased SC was found between the amygdala and ACC in ESRD patients. This indicated that structural changes in the amygdala may be related to the GMV alterations in the ACC. Additionally, decreased FC between the amygdala and ACC was revealed in ESRD patients. Negative correlation was found between the FC of the amygdala-ACC and reaction delay during the Stroop test, but this correlation disappeared after controlling BDI. Stepwise regression analysis showed that the low level of hemoglobin was contributed to the reduced FC of the amygdala-ACC in ESRD patients. Our results demonstrated the abnormal interaction between depressive mood and cognitive control deficits in ESRD patients.

Brain structural properties predict psychologically mediated hypoalgesia in an 8-week sham acupuncture treatment for migraine.

Neuroimaging studies described brain structural changes that comprise the mechanisms underlying individual differences in migraine development and maintenance. However, whether such interindividual variability in migraine was observed in a pretreatment scan is a predisposition for subsequent hypoalgesia to placebo treatment that remains largely unclear. Using T1-weighted imaging, we investigated this issue in 50 healthy controls (HC) and 196 patients with migraine without aura (MO). An 8-week double-blinded, randomized, placebo-controlled acupuncture was used, and we only focused on the data from the sham acupuncture group. Eighty patients participated in an 8-weeks sham acupuncture treatment, and were subdivided (50% change in migraine days from baseline) into recovering (MOr) and persisting (MOp) patients. Optimized voxel-based morphometry (VBM) and functional connectivity analysis were performed to evaluate brain structural and functional changes. At baseline, MOp and MOr had similar migraine activity, anxiety and depression; reduced migraine days were accompanied by decreased anxiety in MOr. In our findings, the MOr group showed a smaller volume in the left medial prefrontal cortex (mPFC), and decreased mPFC-related functional connectivity was found in the default mode network. Additionally, the reduction in migraine days after placebo treatment was significantly associated with the baseline gray matter volume of the mPFC which could also predict post-treatment groups with high accuracy. It indicated that individual differences for the brain structure in the pain modulatory system at baseline served as a substrate on how an individual facilitated or diminished hypoalgesia responses to placebo treatment in migraineurs. Hum Brain Mapp 38:4386-4397, 2017. © 2017 Wiley Periodicals, Inc.

Integration of white matter network is associated with interindividual differences in psychologically mediated placebo response in migraine patients.

Individual differences of brain changes of neural communication and integration in the modular architecture of the human brain network exist for the repeated migraine attack and physical or psychological stressors. However, whether the interindividual variability in the migraine brain connectome predicts placebo response to placebo treatment is still unclear. Using DTI and graph theory approaches, we systematically investigated the topological organization of white matter networks in 71 patients with migraine without aura (MO) and 50 matched healthy controls at three levels: global network measure, nodal efficiency, and nodal intramodule/intermodule efficiency. All patients participated in an 8-week sham acupuncture treatment to induce analgesia. In our results, 30% (n = 21) of patients had 50% change in migraine days from baseline after placebo treatment. At baseline, abnormal increased network integration was found in MO patients as compared with the HC group, and the increased global efficiency before starting clinical treatment was associated with their following placebo response. For nodal efficiency, significantly increased within-subnetwork nodal efficiency and intersubnetwork connectivity of the hippocampus and middle frontal gyrus in patients' white matter network were correlated with the responses of follow-up placebo treatment. Our findings suggested that the trait-like individual differences in pain-related maladaptive stress interfered with and diminished the capacity of chronic pain modulation differently, and the placebo response for treatment could be predicted from a prior white matter network modular structure in migraineurs. Hum Brain Mapp 38:5250-5259, 2017. © 2017 Wiley Periodicals, Inc.

Altered white matter microarchitecture in the cingulum bundle in women with primary dysmenorrhea: A tract-based analysis study.

Primary dysmenorrhea (PD), as characterized by painful menstrual cramps without organic causes, is associated with central sensitization and brain function changes. Previous studies showed the integrated role of the default mode network (DMN) in the pain connectome and its key contribution on how an individual perceives and copes with pain disorders. Here, we aimed to investigate whether the cingulum bundle connecting hub regions of the DMN was disrupted in young women with PD. Diffusion tensor imaging was obtained in 41 PD patients and 41 matched healthy controls (HC) during their periovulatory phase. The production of prostaglandins (PGs) was obtained in PD patients during their pain-free and pain phases. As compared with HC, PD patients had similar scores of pain intensity, anxiety, and depression in their pain-free phase. However, altered white matter properties mainly located in the posterior section of the cingulum bundle were observed in PD. Besides PGs being related to menstrual pain, a close relationship was found between the white matter properties of the cingulum bundle during the pain-free phase and the severity of the menstrual pain in PD patients. Our study suggested that PD had trait changes of white matter integrities in the cingulum bundle that persisted beyond the time of menstruation. We inferred that altered anatomical connections may lead to less-flexible communication within the DMN, and/or between the DMN and other pain-related brain networks, which may result in the central susceptibility to develop chronic pain conditions in PD's later life. Hum Brain Mapp 38:4430-4443, 2017. © 2017 Wiley Periodicals, Inc.

Genetic contribution of catechol-O-methyltransferase in hippocampal structural and functional changes of female migraine sufferers.

Physiological and emotional stressors are associated with or provoke each migraine attack and cause structural and functional changes in the central nervous system. The hippocampus, a limbic structure important in anxiety-related behavior, is vulnerable to long-term stress. Given that catechol-O-methyltransferase (COMT) is widely distributed in the hippocampus and its genetic variation is thought to contribute to the interindividual variability in pain perception and anxiety regulation, whether or not migraine and COMT val(158) met genotype have an interactive effect in the key brain area related to maladaptive stress, the hippocampus, is still poorly understood. Using T1-weighted and resting functional MRI, we evaluated the effect of COMT genetic variations on migraine and possible interactions between COMT and the disease in brain structure and function in 135 females with migraine without aura (MWoA) and 111 matched health controls (HC). Optimized voxel-based morphometry (VBM) and functional connectivity (FC) analyses were applied. From the whole brain VBM analysis, we found a significant disease × genotype interaction in the hippocampus, which overlapped with disease-related increase of gray matter (GM) in val homozygote migraineurs. In our results, increased GM in the hippocampus was only found in val homozygote MWoA compared to val homozygote HC. Moreover, FC between the hippocampus and the medial prefrontal cortex was significantly decreased in val homozygotes, and it was negatively correlated with self-rating anxiety scale values.Our results indicated that brain structure and function of the hippocampus are differentially affected by migraine in val homozygotes compared with met carriers.

Reduced cortical complexity in patients with end-stage kidney disease prior to dialysis initiation.

End-stage kidney disease (ESKD) is associated with cognitive impairment (CI) and affects different aspects of cortical morphometry, but where these changes converge remains unclear. Fractal dimension (FD) is used to represent cortical complexity (CC), which describes the structural complexity of the cerebral cortex by integrating different cortical morphological measures. This study aimed to investigate changes in CC in patients with ESKD prior to initiation of dialysis and to evaluate the relationship between changes in CC, cognitive performance, and uremic toxins. Forty-nine patients with ESKD naive to dialysis and 31 healthy controls (HCs) were assessed using structural magnetic resonance imaging (MRI) and cognitive tests, including evaluations of global cognitive function, memory, and executive function. Clinical laboratory blood tests were performed on all patients with ESKD, including measurement of nine uremic toxin-related indices. CC was measured using MRI data to determine regional FD values. We estimated the association between cognitive performance, uremic toxin levels, and CC changes. Compared to HCs, patients with ESKD showed significantly lower CC in the left precuneus (p = 0.006), left middle temporal cortex (p = 0.010), and left isthmus cingulate cortex (p = 0.018). Furthermore, lower CC in the left precuneus was associated with impaired long-term delayed memory (Pearson r = 0.394, p = 0.042) in patients with ESKD. Our study suggests that regional decreases in CC are an additional characteristic of patients with ESKD naive to dialysis, related to impaired long-term memory performance. These findings may help further understand the underlying neurobiological mechanisms between brain structural changes and CI in patients with ESKD.

The effects of long-term menstrual pain on pain empathy in women with primary dysmenorrhea.

ABSTRACT: Primary dysmenorrhea (PDM) is not only a painful experience but also affects the psychological and affective states of women. Neuroimaging studies have revealed shared neural substrates for somatic and empathic pains in healthy subjects. However, little is known about the relationship between pain intensity and pain empathy in pain disorders. The cyclic nature of PDM makes it a unique model for investigating this issue during a patients' pain phase. To study how long-term pain modulates empathy for pain, T1-weighted magnetic resonance imaging scans were obtained in 39 PDM patients and 41 matched female healthy controls during menstruation. Subjects viewed static visual stimuli of the limbs submitted to painful and nonpainful stimulation to solicit empathy. The visual analogue scale for pain intensity and the Interpersonal Reactivity Index for empathic ability were also obtained. We found that women with PDM exhibited higher pain empathy compared with controls. The anterior insula and brain regions related to sensory discrimination with decreased gray matter volumes were not only shared but also acted as a mediator between pain intensity and pain empathy in PDM patients. In addition, the general linear modeling analysis revealed that long-term pain experience was a more important factor to pain empathy compared with pain intensity. This indicated that long-term pain may cause maladaptive brain structural plasticity, which may further affect psychological adjustment to bring patients more vivid pain when they witness suffering and distress in others.

Neurological effects of hemodialysis on white matter microstructure in end-stage renal disease.

OBJECTIVES: To detect the effects of hemodialysis (HD) on the central nervous system (CNS), the present study forces the memory storage capacity and the difference in white matter (WM) microstructure characteristics among end-stage renal disease (ESRD) participants before HD initiation (ESRD-BHD), ESRD participants with maintenance HD (ESRD-MHD), and healthy participants (HCs). METHODS: Between 2016 and 2018, 56 ESRD-BHD, 39 ESRD-MHD, and 56 HCs were recruited for this study. The fractional anisotropy (FA) of tractography streamlines within the working memory network was investigated using a novel along-tracts analysis method. The relationship between WM microstructure and working memory scores, measured from an n-back task, were detected by multiple correlation analysis. RESULTS: As compared with HCs, a significantly lower FA was found along part of the WM in the working memory network in ESRD-BHD. In the group-difference location of ESRD-BHD and HCs, the FA of ESRD-MHD was reversed to normal levels in HCs. However, the FA in a new location was differentially reduced across groups: highest in HCs, intermediate in ESRD-BHD, and lowest in ESRD-MHD. Correlation analysis showed that a longer reaction time correlated to a lower FA, according to the following pattern: ESRD-BHD > ESRD-MHD > HCs. CONCLUSION: Despite the persisting abnormal brain structure, our findings suggest HD has a neuroprotective effect in ESRD patients.

Neurovascular coupling dysfunction in end-stage renal disease patients related to cognitive impairment.

We aimed to investigate the neurovascular coupling (NVC) dysfunction in end-stage renal disease (ESRD) patients related with cognitive impairment. Twenty-five ESRD patients and 22 healthy controls were enrolled. To assess the NVC dysfunctional pattern, resting-state functional MRI and arterial spin labeling were explored to estimate the coupling of spontaneous neuronal activity and cerebral blood perfusion based on amplitude of low-frequency fluctuation (ALFF)-cerebral blood flow (CBF), fractional ALFF (fALFF)-CBF, regional homogeneity (ReHo)-CBF, and degree centrality (DC)-CBF correlation coefficients. Multivariate partial least-squares correlation and mediation analyses were used to evaluate the relationship among NVC dysfunctional pattern, cognitive impairment and clinical characteristics. The NVC dysfunctional patterns in ESRD patients were significantly decreased in 34 brain regions compared with healthy controls. The decreased fALFF-CBF coefficients in the cingulate gyrus (CG) were associated positively with lower kinetic transfer/volume urea (Kt/V) and lower short-term memory scores, and were negatively associated with higher serum urea. The relationship between Kt/V and memory deficits of ESRD patients was partially mediated by the fALFF-CBF alteration of the CG. These findings reveal the NVC dysfunction may be a potential neural mechanism for cognitive impairment in ESRD. The regional NVC dysfunction may mediate the impact of dialysis adequacy on memory function.

White matter characteristics between amygdala and prefrontal cortex underlie depressive tendency in end stage renal disease patients before the dialysis initiation.

Depression is one of the common incidental symptoms in end-stage renal disease (ESRD) patients, empirically overlooked. Reproducible results observed that altered interregional white matter (WM) connections between depression-related brain regions (thalamus, amygdala, and prefrontal cortex (PFC)) in the human brain were closely associated with depression. Whether the depressive tendency of ESRD patients is also association with the WM connections is remains unknown. To address this problem, 56 ESRD patients before dialysis initiation and 56 healthy controls (HCs) were scanned with diffusion tensor imaging. According to the diagnostic and statistical manual of mental disorders, ESRD patients were separated into with and without depressive tendency groups. Twenty-five essential metabolites were tested in ESRD. The tractography atlas-based analysis and multiple regression analysis were implemented to gain features which could map the depressive tendency variability across ESRD. For metabolites, the levels of thrombocytes and calcium have significant differences between with and without depressive tendency groups. For WM microstructure, depressive tendency ESRD patients had abnormal WM diffusion properties along the fiber tracts of the amygdala-PFC. Compared with the features which were extracted from the group-difference of WM or metabolites, only WM features combinations (1000 bootstrap samples; 5000 permutation tests) along the fiber tract of the amygdala-PFC was a significant predictor of either with or without depressive tendency. Our findings suggested that the advanced neuroprotection may be planned before dialysis initiation, and the WM characteristics of amygdala-PFC may be a potential neuromarkers for the early diagnosis of depressive tendency in ESRD patients before dialysis initiation.

The variation of motor-related brain structure and its relation to abnormal motor behaviors in end-stage renal disease patients with restless legs syndrome.

Restless legs syndrome (RLS) is common in the end-stage renal disease (ESRD) population; however, their interrelationship remains largely unclear. In the current study, we aimed to investigate the brain structure variation in ESRD patients with RLS (ERSD-RLS) and its potential relation with the severity of RLS. Diffusion tensor imaging and T1-weighted imaging were obtained from 64 ERSD-RLS and 64 matched healthy controls. Voxel-based morphometry (VBM) analysis and tractography atlas-based analysis (TABS) were used to detect the alteration of gray matter (GM) volume and white matter (WM) microstructural characterization. The corticospinal tract (CST), which is a main motor-pathway, was selected as a fiber bundle of interest in the TABS analysis. The severity of RLS was evaluated by using the International RLS Study Group scale. Lastly, a correlation analysis was performed to explore the interrelationship between RLS rating scores and brain structure measurements. For the results, ERSD-RLS showed abnormal GM volume of motor-related brain regions located in the bilateral superior frontal gyri, precentral gyrus, and putamen. Significant differences in the diffusion properties were found at the posterior limb of the internal capsule. Furthermore, the severity of RLS was only significantly associated with the diffusion properties, which was not found in the motor-related regions of GM. Our results suggest that the motor-related brain structure was altered in ERSD-RLS. The abnormal WM microstructure of the CST may serve as an imaging marker correlated with the severity of motor dysfunction in ERSD-RLS, indicating that WM neuroprotection should be considered when improving motor function in ERSD-RLS.