Salience Network Functional Connectivity Research Articles

Integration patterns of functional brain networks can predict the response to abdominal acupuncture in patients with major depressive disorder

Abdominal acupuncture has definite efficacy for major depressive disorder (MDD). Our study examined how abdominal acupuncture regulates the integration within and between brain networks of MDD patients by neuroimaging and whether this functional integration can predict the efficacy. Forty-six female MDD patients were randomly divided into a fluoxetine + real acupuncture group (n = 22) and a fluoxetine + sham acupuncture group (n = 24). The differences in functional magnetic resonance imaging data in the intra- and inter-network functional connectivity (FC) of the default mode network (DMN), affective network (AN), salience network (SN), and cognitive control network (CCN) between the two groups were analyzed. The FCs in brain regions with the inter-group differences and support vector regression were used to predict the efficacy of abdominal acupuncture. Our results showed: that the intra- and inter-network FCs of DMN, AN, SN, and CCN could be changed by abdominal acupuncture. Using the baseline FCs within AN and DMN or AN–DMN as characteristics, combined with support vector regression, could better predict the efficacy of acupuncture. Our study suggests that abdominal acupuncture could treat MDD by regulating the integration of the functional networks DMN, AN, SN, and CCN. The baseline FCs within the DMN and AN or between them could be used as neural markers for predicting the efficacy of abdominal acupuncture.

Effects of mini-basketball training program on social communication impairments and salience network in preschool children with autism spectrum disorder

Objectives This study aims to explore the impact of a 12-week mini-basketball training program (MBTP) on social communication impairments and salience network in preschool children with autism spectrum disorder (ASD), and to reveal the potential neural mechanisms by which MBTP improves social communication impairments in ASD children. Methods 34 ASD children aged 3–6 were assigned to the experimental group (n = 19) or the control group (n = 15). The experimental group received MBTP for 12 wk, while the control group received routine behavioral rehabilitation interventions from institutions. Social communication impairments in preschool ASD children is measured with the Social Response Scale Second Edition (SRS-2). Functional connectivity of salience network before and after testing is evaluated by resting-state functional magnetic resonance imaging (rs-fMRI). Results This study suggests improvement in the social cognitive dimension of preschool ASD children with the aid of MBTP as well as optimization of the functional connectivity of ASD children’s salience network. The potential neural mechanism of MBTP in improving social cognitive dimension in ASD children involved changes in functional connectivity in the left middle frontal gyrus and left thalamus. Conclusions This study infers that the MBTP may not improve the social communication impairments of the ASD children while it is likely to improve social cognitive aspect of social communication impairments and reduce the maladaptive traits of ASD children. Under this circumstance, the study could provide new evidence to explore the neural mechanisms of physical exercise improving social communication impairments and new targets for developing exercise intervention programs to improve social communication impairments in ASD children.

Longitudinal neurofunctional changes in medication overuse headache patients after mindfulness practice in a randomized controlled trial (the MIND-CM study)

BackgroundMindfulness practice has gained interest in the management of Chronic Migraine associated with Medication Overuse Headache (CM-MOH). Mindfulness is characterized by present-moment self-awareness and relies on attention control and emotion regulation, improving headache-related pain management. Mindfulness modulates the Default Mode Network (DMN), Salience Network (SN), and Fronto-Parietal Network (FPN) functional connectivity. However, the neural mechanisms underlying headache-related pain management with mindfulness are still unclear. In this study, we tested neurofunctional changes after mindfulness practice added to pharmacological treatment as usual in CM-MOH patients.MethodsThe present study is a longitudinal phase-III single-blind Randomized Controlled Trial (MIND-CM study; NCT03671681). Patients had a diagnosis of CM-MOH, no history of neurological and severe psychiatric comorbidities, and were attending our specialty headache centre. Patients were divided in Treatment as Usual (TaU) and mindfulness added to TaU (TaU + MIND) groups. Patients underwent a neuroimaging and clinical assessment before the treatment and after one year. Longitudinal comparisons of DMN, SN, and FPN connectivity were performed between groups and correlated with clinical changes. Vertex-wise analysis was performed to assess cortical thickness changes.Results177 CM-MOH patients were randomized to either TaU group or TaU + MIND group. Thirty-four patients, divided in 17 TaU and 17 TaU + MIND, completed the neuroimaging follow-up. At the follow-up, both groups showed an improvement in most clinical variables, whereas only TaU + MIND patients showed a significant headache frequency reduction (p = 0.028). After one year, TaU + MIND patients showed greater SN functional connectivity with the left posterior insula (p-FWE = 0.007) and sensorimotor cortex (p-FWE = 0.026). In TaU + MIND patients only, greater SN-insular connectivity was associated with improved depression scores (r = -0.51, p = 0.038). A longitudinal increase in cortical thickness was observed in the insular cluster in these patients (p = 0.015). Increased anterior cingulate cortex thickness was also reported in TaU + MIND group (p-FWE = 0.02).ConclusionsIncreased SN-insular connectivity might modulate chronic pain perception and the management of negative emotions. Enhanced SN-sensorimotor connectivity could reflect improved body-awareness of painful sensations. Expanded cingulate cortex thickness might sustain improved cognitive processing of nociceptive information. Our findings unveil the therapeutic potential of mindfulness and the underlying neural mechanisms in CM-MOH patients.Trial RegistrationName of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018

Plasma Neurofilament Light Relates to Divergent Default and Salience Network Connectivity in Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) show differential vulnerability to large-scale brain functional networks. Plasma neurofilament light (NfL), a promising biomarker of neurodegeneration, has been linked in AD patients to glucose metabolism changes in AD-related regions. However, it is unknown whether plasma NfL would be similarly associated with disease-specific functional connectivity changes in AD and bvFTD. Our study examined the associations between plasma NfL and functional connectivity of the default mode and salience networks in patients with AD and bvFTD. Plasma NfL and neuroimaging data from patients with bvFTD (n = 16) and AD or mild cognitive impairment (n = 38; AD + MCI) were analyzed. Seed-based functional connectivity maps of key regions within the default mode and salience networks were obtained and associated with plasma NfL in these patients. We demonstrated divergent associations between NfL and functional connectivity in AD + MCI and bvFTD patients. Specifically, AD + MCI patients showed lower default mode network functional connectivity with higher plasma NfL, while bvFTD patients showed lower salience network functional connectivity with higher plasma NfL. Further, lower NfL-related default mode network connectivity in AD + MCI patients was associated with lower Montreal Cognitive Assessment scores and higher Clinical Dementia Rating sum-of-boxes scores, although NfL-related salience network connectivity in bvFTD patients was not associated with Neuropsychiatric Inventory Questionnaire scores. Our findings indicate that plasma NfL is differentially associated with brain functional connectivity changes in AD and bvFTD.

Salience Network Functional Connectivity Mediates Association Between Social Engagement and Cognition in Non-Demented Older Adults: Exploratory Investigation.

Social engagement has beneficial effects during cognitive aging. Large-scale cognitive brain network functions are implicated in both social behaviors and cognition. We evaluated associations between functional connectivity (FC) of large-scale brain cognitive networks and social engagement, characterized by self-reported social network size and contact frequency. We subsequently tested large-scale brain network FC as a potential mediator of the beneficial relationship between social engagement and cognitive performance. 112 older adults (70.7±7.3 years, range 54.6-89.7; 84 women) completed the Lubben Social Network Scale 6 (LSNS-6), National Alzheimer's Coordinating Center (NACC) Uniform Data Set 3 (UDS-3) cognitive battery, and resting state fMRI. We completed seed-based correlational analysis in the default mode and salience networks. Significant associations between social engagement scores and cognitive performance, as well as between social engagement and FC of brain networks, informed the construction of mediation models. Social engagement was significantly associated with executive function and global cognition, with greater social engagement associated with better cognitive performance. Social engagement was significantly associated with salience network FC, with greater social engagement associated with higher connectivity. Salience network FC partially mediated associations between social engagement and both executive function and global cognition. Our results suggest that the salience network is a key mediator of the beneficial relationship between social engagement and cognition in older adults.

Homeostatic NREM sleep and salience network function in adult mice exposed to ethanol during development.

Developmental exposure to ethanol is a leading cause of cognitive, emotional and behavioral problems, with fetal alcohol spectrum disorder (FASD) affecting more than 1:100 children. Recently, comorbid sleep deficits have been highlighted in these disorders, with sleep repair a potential therapeutic target. Animal models of FASD have shown non-REM (NREM) sleep fragmentation and slow-wave oscillation impairments that predict cognitive performance. Here we use a mouse model of perinatal ethanol exposure to explore whether reduced sleep pressure may contribute to impaired NREM sleep, and compare the function of a brain network reported to be impacted by insomnia-the Salience network-in developmental ethanol-exposed mice with sleep-deprived, saline controls. Mice were exposed to ethanol or saline on postnatal day 7 (P7) and allowed to mature to adulthood for testing. At P90, telemetered cortical recordings were made for assessment of NREM sleep in home cage before and after 4 h of sleep deprivation to assess basal NREM sleep and homeostatic NREM sleep response. To assess Salience network functional connectivity, mice were exposed to the 4 h sleep deprivation period or left alone, then immediately sacrificed for immunohistochemical analysis of c-Fos expression. The results show that developmental ethanol severely impairs both normal rebound NREM sleep and sleep deprivation induced increases in slow-wave activity, consistent with reduced sleep pressure. Furthermore, the Salience network connectome in rested, ethanol-exposed mice was most similar to that of sleep-deprived, saline control mice, suggesting a sleep deprivation-like state of Salience network function after developmental ethanol even without sleep deprivation.

Sex-Related Disparities in the Resting State Functional Connectivity of the Locus Coeruelus and Salience Network in Preclinical Alzheimer's Disease.

Recent studies have demonstrated the pivotal role of locus coeruleus (LC) and salience network (SN) resting state functional connectivity (rsFC) changes in the early stage of Alzheimer's disease (AD). Moreover, sex has been a crucial point of discussion in understanding AD pathology. We aimed to demonstrate the sex-related disparities in the functional connectivity (FC) of the SN and LC in preclinical AD. A total of 89 cognitively normal patients with evidence of amyloid beta (Aβ) accumulation ([18F] flutemetamol +) were recruited in the study. A seed-to-voxel analysis was conducted to measure the LC and SN rsFC differences between sexes. In addition, sex by Aβ interactive effects on FC values were analyzed with a general linear model. There were statistically significant sex by regional standardized uptake value ratio (SUVR) interactions in the LC FC with the parietal, frontal, and occipital cortices. Moreover, there was a significant sex by global SUVR interaction in the SN FC with the temporal cortex. The findings suggest that there are differential patterns of LC FC and SN FC in males and females with preclinical AD, which interact with regional Aβ deposition.

Differential associations between plasma neurofilament light and brain functional connectivity in patients with Alzheimer’s disease and fronto‐temporal dementia

AbstractBackgroundNeurofilament light chain (NfL), a marker of axonal loss, is elevated in both Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD)[1‐6]. AD and bvFTD have been shown to spread along specific networks reflective of their symptom profiles[7,8], with AD associated with declines in default mode network (DMN) functional connectivity (FC), and bvFTD linked to disruptions in salience network (SN) FC[9]. However, the association between plasma NfL and FC in these two groups remains unknown. Given evidence linking plasma NfL to hypometabolism in circumscribed regions within the DMN in mild cognitive impairment (MCI) patients[10], we hypothesize that NfL would similarly be associated with FC in a network‐specific manner in AD and bvFTD.MethodPlasma NfL and neuroimaging data from young‐onset patients with bvFTD (n = 16) and AD (n = 38; including AD and MCI of AD type (AD+MCI)) were analyzed. Plasma NfL was measured by single molecule array (SIMOA). Seed‐based FC maps using regions‐of‐interest from DMN (left posterior cingulate cortex) and SN (right anterior insula) were derived for each patient. Voxelwise analyses examining associations between plasma NfL and seed‐based FC were first performed in each group separately. Clusters showing significant FC‐NfL associations were then examined for group differences between AD+MCI and bvFTD, and correlated with neuropsychological performance. All analyses accounted for age, sex, education, handedness and total intracranial volumes.ResultsWe demonstrated differential associations between plasma NfL and FC in AD+MCI and bvFTD patients: AD+MCI patients showed significantly lower DMN FC with higher plasma NfL compared to bvFTD patients (Figure 1A), while bvFTD patients showed lower SN FC (Figure 1B) with higher plasma NfL relative to AD+MCI patients. Further, lower NfL‐related DMN FC in AD+MCI patients was significantly associated with lower MoCA scores (Figure 2).ConclusionPlasma NfL is associated with FC changes in a network‐specific manner in bvFTD and AD+MCI patients, which may be in turn be predictive of cognitive decline. Our study suggest that axonal protein loss has differential effects on functional brain networks in different dementia subtypes. Future studies are warranted to confirm these findings in a larger cohort.

Effects of integrated hospital treatment on the default mode, salience, and frontal-parietal networks in anorexia nervosa: A longitudinal resting-state functional magnetic resonance imaging study.

The psychopathology of patients with anorexia nervosa has been hypothesized to involve inappropriate self-referential processing, disturbed interoceptive awareness, and excessive cognitive control, including distorted self-concern, disregard of their own starvation state, and extreme weight-control behavior. We hypothesized that the resting-state brain networks, including the default mode, salience and frontal-parietal networks, might be altered in such patients, and that treatment might normalize neural functional connectivity, with improvement of inappropriate self-cognition. We measured resting-state functional magnetic resonance images from 18 patients with anorexia nervosa and 18 healthy subjects before and after integrated hospital treatment (nourishment and psychological therapy). The default mode, salience, and frontal-parietal networks were examined using independent component analysis. Body mass index and psychometric measurements significantly improved after treatment. Before treatment, default mode network functional connectivity in the retrosplenial cortex and salience network functional connectivity in the ventral anterior insula and rostral anterior cingulate cortex were decreased in anorexia nervosa patients compared with those in controls. Interpersonal distrust was negatively correlated with salience network functional connectivity in the rostral anterior cingulate cortex. Default mode network functional connectivity in the posterior insula and frontal-parietal network functional connectivity in the angular gyrus were increased in anorexia nervosa patients compared with those in controls. Comparison between pre- and post-treatment images from patients with anorexia nervosa exhibited significant increases in default mode network functional connectivity in the hippocampus and retrosplenial cortex, and salience network functional connectivity in the dorsal anterior insula following treatment. Frontal-parietal network functional connectivity in the angular cortex showed no significant changes. The findings revealed that treatment altered the functional connectivity in several parts of default mode and salience networks in patients with anorexia nervosa. These alterations of neural function might be associated with improvement of self-referential processing and coping with sensations of discomfort following treatment for anorexia nervosa.

385. Exposure to Particulate Matter is Associated With Altered Salience Network Functional Connectivity and Internalizing Symptoms in Youth

385. Exposure to Particulate Matter is Associated With Altered Salience Network Functional Connectivity and Internalizing Symptoms in Youth

Sex differences in functional brain networks involved in interoception: An fMRI study.

Interoception can be described as the ability to perceive inner body sensations and it is different between biological sex. However, no previous research correlated this ability with brain functional connectivity (FC) between males and females. In this study, we used resting-state functional magnetic resonance imaging to investigate FC of networks involved in interoception among males and females in a sample of healthy volunteers matched for age. In total, 67 participants (34 females, mean age 44.2; 33 males, mean age 37.2) underwent a functional MRI session and completed the Self-Awareness Questionnaire (SAQ) that tests the interoceptive awareness. To assess the effect of sex on scores obtained on the SAQ we performed a multivariate analysis of variance. A whole-brain seed-to-seed FC analysis was conducted to investigate the correlation between SAQ score and FC, and then to test differences in FC between males and females with SAQ score as a covariate. MANOVA revealed a significant difference in SAQ scores between males and females with higher values for the second ones. Also, significant correlations among interoception scores and FC in Salience network and fronto-temporo-parietal brain areas have been detected, with a sharp prevalence for the female. These results support the idea of a female advantage in the attention toward interoceptive sensations, suggesting common inter-network areas that concur to create the sense of self.

Altered Functional Connectivity of Salience Network in Mood Disorders

IntroductionDespite the significant scientific progress in the study of the mechanisms underlying mental disorders, stable biomarkers facilitating their diagnosis and differential diagnosis are lacking. Therefore, we attempted to explore possible functional connectivity (FC) differences across some of the more prevalent mental disorders, namely mood disorders.ObjectivesThe current study aimed at investigating the alterations of the functional connectivity of major seeds of the Salience Network (SN) (the Anterior Cingulate Cortex (ACC), and Anterior Insula (AI) in patients with unipolar (Major Depressive Disorder-MDD) or bipolar (Bipolar Disorder-BD) depression as compared to healthy controls (HC).MethodsFor this study 103 adult subjects underwent resting-state Magnetic Resonance Imaging of whom 60 were patients with a depressive episode (MDD: n=35; BD: n=25), and 43 were healthy controls (HC). The individuals in both groups were matched for age and gender. Each participant has provided written informed consent (Ethics Committee: P186/22.01.2021). Seed-to-voxel analysis was performed via the CONN toolbox running on MATLAB. Random Field Theory parametric statistics was used with a cluster-level FWE correction p<0.05.ResultsBoth the ACC and the right AI demonstrated a statistically significant increase in the FC to the somatosensory cortex and the motor cortex in patients as opposed to HC. In addition, there was hyperconnectivity between ACC and the right Superior Frontal Gyrus, Precuneus, and the Superior Parietal Lobule bilaterally in patients as well. A reduced FC between the ACC and the hippocampus and parahippocampus was observed in depression in comparison to HC. The analysis of the left AI seed yielded no statistically significant between-group differences.ConclusionsOur results demonstrate aberrant connectivity between nodes of the SN, the Default Mode Network, and the Limbic Network which might provide clarification on the mechanisms of impaired balance between internally and externally oriented attention, affective and cognitive control in depression. In addition, the alterations of the FC between SN and the somatosensory and motor cortices may be suggested as a possible explanation of the disturbances in the psychomotor activity in mood disorders.Disclosure of InterestA. Todeva-Radneva Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, R. Paunova Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, D. Stoyanov Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, T. Zdravkova Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience, S. Kandilarova Grant / Research support from: This work has been funded by the Bulgarian National Program “European Scientific Networks” - Project DIP Neuroscience

Decreased functional connectivity in salience network is associated with symptom severity in betel quid-dependent chewers.

Betel quid (BQ) is the fourth most popular psychoactive agent worldwide. Neuroimaging studies have showed that substance-addicted individuals including alcohol, heroin, nicotine and other addictive substance exhibit altered activity patterns of the salience network (SN). However, no study has yet investigated the neural correlates of the resting-state SN and BQ dependence (BQD)-related physiopathological characteristics. Thirty-two BQ-dependent (BQD) chewers and 32 healthy controls were recruited to participate in this study. Resting-state functional magnetic resonance imaging (fMRI) data were analysed by independent component analysis (ICA). BQD chewers exhibited decreased functional connectivity in bilateral insula, anterior cingulate cortex (ACC), medial superior frontal gyrus (MSFG) and inferior orbital frontal gyrus (IOFG) [false discovery rate (FDR) correction, p < 0.05]. In the BQD group, the decreased functional connectivity in left ACC correlated negatively with BQDS (BQD Scale) and the duration of BQ. We reported decreased functional connectivity in resting-state SN of BQD individuals. The decreased functional connectivity in left ACC correlated negatively with BQDS and the duration of BQ. Our findings provided evidence for the importance of the SN in the pathophysiology of BQD and indicated that the SN dysfunction might provide a potential mechanism in BQD development.

Distinct patterns of functional brain network integration between treatment-resistant depression and non treatment-resistant depression: A resting-state functional magnetic resonance imaging study

BackgroundPrevious neuroimaging has paid little attention to the differences in brain network integration between patients with treatment-resistant depression(TRD) and non-TRD (nTRD), and the relationship between their impaired brain network integration and clinical symptoms has not been elucidated. MethodEighty one major depressive disorder (MDD) patients (40 in TRD, 41 in nTRD) and 40 healthy controls (HCs) were enrolled for the functional magnetic resonance imaging (fMRI) scans. A seed-based functional connectivity (FC) method was used to investigate the brain network abnormalities of default mode network (DMN), affective network (AN), salience network (SN) and cognitive control network (CCN) for the MDD. Finally, the correlation was analyzed between the abnormal FCs and 17-item Hamilton Rating Scale for Depression scale (HAMD-17) scores. ResultsCompared with the HC group, the FCs in DMN, AN, SN, CCN were altered in both the TRD and nTRD groups. Compared with the nTRD group, FC alterations in the AN and CCN were more abnormal in the TRD group, and the FC alterations were generally decreased at the SN in the TRD group. In addition, the FC values of right dorsolateral prefrontal cortices and left caudate nucleus in the TRD group and the FC values of right subgenual anterior cingulate cortex and left middle temporal gyrus in the nTRD group were positively correlated with HAMD-17 scale scores. ConclusionsAbnormal FCs are present in four brain networks (DMN, AN, SN, CCN) in both the TRD and nTRD groups. Except of DMN, FCs in AN, SN and CCN maybe underlay the neurobiological mechanism in differentiating TRD from nTRD.

Structural and Functional Brain Connectivity Uniquely Contribute to Episodic Memory Performance in Older Adults.

In this study, we examined the independent contributions of structural and functional connectivity markers to individual differences in episodic memory performance in 107 cognitively normal older adults from the BIOCARD study. Structural connectivity, defined by the diffusion tensor imaging (DTI) measure of radial diffusivity (RD), was obtained from two medial temporal lobe white matter tracts: the fornix and hippocampal cingulum, while functional connectivity markers were derived from network-based resting state functional magnetic resonance imaging (rsfMRI) of five large-scale brain networks: the control, default, limbic, dorsal attention, and salience/ventral attention networks. Hierarchical and stepwise linear regression methods were utilized to directly compare the relative contributions of the connectivity modalities to individual variability in a composite delayed episodic memory score, while also accounting for age, sex, cerebrospinal fluid (CSF) biomarkers of amyloid and tau pathology (i.e., Aβ42/Aβ40 and p-tau181), and gray matter volumes of the entorhinal cortex and hippocampus. Results revealed that fornix RD, hippocampal cingulum RD, and salience network functional connectivity were each significant independent predictors of memory performance, while CSF markers and gray matter volumes were not. Moreover, in the stepwise model, the addition of sex, fornix RD, hippocampal cingulum RD, and salience network functional connectivity each significantly improved the overall predictive value of the model. These findings demonstrate that both DTI and rsfMRI connectivity measures uniquely contributed to the model and that the combination of structural and functional connectivity markers best accounted for individual variability in episodic memory function in cognitively normal older adults.

Resting-state functional connectivity of salience network in schizophrenia and depression

To explore the salience network (SN) functional alterations in schizophrenia and depression, resting-state functional magnetic resonance imaging (rs-fMRI) data from 29 patients with schizophrenia (SCH), 28 patients with depression (DEP) and 30 healthy controls (HC) were obtained. The SN was derived from data-driven group independent component analysis (gICA). ANCOVA and post hoc tests were performed to discover the FC differences of SN between groups. The ANCOVA demonstrated a significant group effect in FC with right inferior and middle temporal gyrus (ITG and MTG), left caudate, and right precentral gyrus. Post-hoc analyses revealed an opposite altered FC pattern between SN and right ITG and MTG for both patient groups. The DEP group showed a reduced FC between SN and right ITG and MTG compared with HC whereas the SCH group showed an increased FC. In addition, the SCH group showed decreased FC between SN and left caudate, and enhanced FC between SN and right precentral gyrus compared to the other two groups. Our findings suggest distinct FC of SN in schizophrenia and depression, supporting that the resting-state FC pattern of SN may be a transdiagnostic difference between depression and schizophrenia and may play a critical role in the pathogenesis of these two disorders.

Altered Structural and Functional Connectivity of Salience Network in Patients with Classic Trigeminal Neuralgia

Classic trigeminal neuralgia (CTN) is a neuropathic pain disorder displaying spontaneously stabbing or electric shock-like paroxysms in the face. Previous research suggests structural and functional abnormalities in brain regions related to sensory and cognitive-affective dimensions of pain contribute to the pathophysiology of CTN. However, few studies to date have investigated how changes in whole-brain functional networks and white matter connectivity are related to CTN. We performed an independent component analysis to examine abnormalities in resting state functional connectivity of large-scale networks in 48 patients with CTN compared to 46 matched healthy participants. Then, diffusion tensor tractography was performed to test whether these alterations of functional connectivity in intrinsic networks were associated with impairment of the white matter tracts connecting them. Distinct patterns of functional connectivity were detected within default mode network, somatosensory network, and salience network (SN) in the CTN group when compared with healthy controls. Furthermore, abnormality of SN was negatively correlated with pain severity. In support of aberrant functional connectivity within SN, structural disintegration was observed in the white matter tract from left anterior insula (aIns) to left anterior cingulate cortex (ACC) in CTN. These results suggest that altered structural and functional connectivity between aIns and ACC may underpin the aberrant SN in patients with CTN and provide an alternative target for clinical interventions. PerspectiveThis article presents distinctive abnormalities of functional and structural connectivity from aIns to ACC in the patients with CTN, which is associated with pain ratings. This measure could potentially provide an alternative target for clinicians to alleviate this type of intermittent and refractory pain.

Impact of autism genetic risk on brain connectivity: a mechanism for the female protective effect.

The biological mechanisms underlying the greater prevalence of autism spectrum disorder in males than females remain poorly understood. One hypothesis posits that this female protective effect arises from genetic load for autism spectrum disorder differentially impacting male and female brains. To test this hypothesis, we investigated the impact of cumulative genetic risk for autism spectrum disorder on functional brain connectivity in a balanced sample of boys and girls with autism spectrum disorder and typically developing boys and girls (127 youth, ages 8-17). Brain connectivity analyses focused on the salience network, a core intrinsic functional connectivity network which has previously been implicated in autism spectrum disorder. The effects of polygenic risk on salience network functional connectivity were significantly modulated by participant sex, with genetic load for autism spectrum disorder influencing functional connectivity in boys with and without autism spectrum disorder but not girls. These findings support the hypothesis that autism spectrum disorder risk genes interact with sex differential processes, thereby contributing to the male bias in autism prevalence and proposing an underlying neurobiological mechanism for the female protective effect.

Right Frontoinsular Cortex: A Potential Imaging Biomarker to Evaluate T2DM-Induced Cognitive Impairment.

Cognitive impairment in type 2 diabetes mellitus (T2DM) is associated with functional and structural abnormalities in the intrinsic brain network. The salience network (SN) is a neurocognitive network that maintains normal cognitive function, but it has received little attention in T2DM. We explored SN changes in patients with T2DM with normal cognitive function (DMCN) and in patients with T2DM with mild cognitive impairment (DMCI). Sixty-five T2DM patients and 31 healthy controls (HCs) underwent a neuropsychological assessment, independent component analysis (ICA), and voxel-based morphometry (VBM) analysis. The ICA extracted the SN for VBM to compare SN functional connectivity (FC) and gray matter (GM) volume (GMV) between groups. A correlation analysis examined the relationship between abnormal FC and GMV and clinical/cognitive variables. Compared with HCs, DMCN patients demonstrated increased FC in the left frontoinsular cortex (FIC), right anterior insula, and putamen, while DMCI patients demonstrated decreased right middle/inferior frontal gyrus FC. Compared with DMCN patients, DMCI patients showed decreased right FIC FC. There was no significant difference in SN GMV in DMCN and DMCI patients compared with HCs. FIC GMV was decreased in the DMCI patients compared with DMCN patients. In addition, right FIC FC and SN GMV positively correlated with Montreal Cognitive Assessment and Mini-Mental State Examination (MMSE) scores. These findings indicate that changes in SN FC, and GMV are complex non-linear processes accompanied by increased cognitive dysfunction in patients with T2DM. The right FIC may be a useful imaging biomarker for supplementary assessment of early cognitive dysfunction in patients with T2DM.

L-Cystine is associated with the dysconnectivity of the default-mode network and salience network in attention-deficit/hyperactivity disorder

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Distributed dysconnectivity within both the default-mode network (DMN) and the salience network (SN) has been observed in ADHD. L-cystine may serve as a neuroprotective molecule and signaling pathway, as well as a biomarker of ADHD. The purpose of this study was to explore whether differential brain network connectivity is associated with peripheral L-cystine levels in ADHD patients. We recruited a total of 31 drug-naïve patients with ADHD (mean age: 10.4 years) and 29 healthy controls (mean age: 10.3 years) that underwent resting state functional magnetic resonance imaging scans. Functional connectomes were generated for each subject, and we examined the cross-sectional group difference in functional connectivity (FC) within and between DMN and SN. L-cystine plasma levels were determined using high-performance chemical isotope labeling (CIL)-based liquid chromatography-mass spectrometry (LC-MS). Compared to the control group, the ADHD group showed decreased FC of dorsal DMN (p = 0.031), as well as decreased FC of precuneus-post SN (p = 0.006) and ventral DMN-post SN (p = 0.001). The plasma L-cystine levels of the ADHD group were significantly higher than in the control group (p = 0.002). Furthermore, L-cystine levels were negatively correlated with FC of precuneus-post SN (r = −0.404, p = 0.045) and ventral DMN-post SN (r = −0.540, p = 0.007). The findings suggest that decreased synergies of DMN and SN may serve as neurobiomarkers for ADHD, while L-cystine may be involved in the pathophysiology of network dysconnectivity. Future studies on the molecular mechanism of the cystine-glutamate system in brain network connectivity are warranted.