Cognition and Ventral Attention Network Connectivity: Associations With Treatment Response in Posttraumatic Stress Disorder.

OBJECTIVE: Posttraumatic stress disorder (PTSD) is a highly heterogeneous disorder, which makes it difficult to link clinical phenotypes with biomarkers to improve treatment outcomes. Findings from previous studies suggest that cognitive measures such as verbal memory or attention paired with within-ventral attention network (VAN) or salience network resting-state functional connectivity may predict treatment response among individuals with PTSD. METHODS: In a sample comprising 20 individuals with PTSD and 10 healthy control group individuals, the investigators subtyped individuals by using both discriminant function analysis and standardized norms for a single measure of memory and neuropsychological batteries of memory, attention, and executive functioning; attempted to replicate previous findings of lower within-VAN connectivity among individuals with cognitive impairment; and explored whether within-VAN connectivity paired with cognitive impairment predicted treatment outcomes. RESULTS: PTSD patients with cognitive impairment (defined by using a discriminant function analysis with verbal memory performance) had greater within-VAN resting-state functional connectivity compared with control group individuals and cognitively intact PTSD patients at a level that fell short of statistical significance (F=3.41; df=2, 21; ηp2=0.237). The interaction between verbal memory performance and within-VAN connectivity also predicted treatment-related change in PTSD symptoms at a level that also fell short of statistical significance (ß=-0.442). CONCLUSIONS: These findings somewhat support the clinical utility of identifying cognitive phenotypes within PTSD (by using discriminant function analysis and verbal memory performance) to predict treatment outcomes.

Deficient salience and default mode functional integration in high worry-proneness subject: a connectome-wide association study.

Worry has been conceptualized as a relatively uncontrollable chain of thought that increases the risk of mental problems, such as anxiety disorders. Here, we examined the link between individual variation in the functional connectome and worry proneness, which remains unclear. A total of 32 high worry-proneness (HWP) subjects and 25 low worry-proneness (LWP) subjects were recruited. We conducted multivariate distance-based matrix regression to identify phenotypic relationships in high-dimensional brain resting-state functional connectivity data from HWP subjects. Multiple hub regions, including key brain nodes of the salience network (SN) and default mode network (DMN), were identified in HWP subjects. Follow-up analyses revealed that a high worry-proneness score was dominated by functional connectivity between the SN and the DMN. Moreover, HWP subjects showed hypoconnectivity between the cerebellum and the SN and DMN compared with LWP subjects. This cross-sectional study could not fully measure the causal relationships between changes in functional networks and worry proneness in healthy subjects. Functional changes in the cerebellum-cortical region might affect the modulation of external stimuli processing. Together, our results provide new insight into the role of key networks, including the SN, DMN and cerebellum, in understanding the potential mechanism underlying the high worry dimension in healthy subjects.

Comparative study on structural and functional brain differences in mild cognitive impairment patients with tinnitus.

Objective: Tinnitus may be associated with various brain changes. However, the degenerative changes in patients with tinnitus have not been extensively investigated. We aimed to evaluate degenerative, structural, and functional brain changes in patients with mild cognitive impairment (MCI) who also suffer from tinnitus. Materials and methods: This study included participants aged 60 to 80 years with MCI and a hearing level better than 40 dB. The participants were classified into two groups: MCI with tinnitus (MCI-T) and MCI without tinnitus (MCI-NT). All patients underwent Tinnitus Handicap Inventory (THI), 3 T brain MRI, F18-florapronol PET, and F18-FDG PET. Results: The MCI-T group exhibited higher ß-amyloid deposition in the superior temporal gyrus, temporal pole, and middle temporal gyrus compared to the MCI-NT group (p < 0.05 for all). Additionally, the MCI-T group showed increased metabolism in the inferior frontal gyrus, insula, and anterior cingulate cortex (ACC) (p < 0.005 for all). The THI score was strongly correlated with increased volume in the insula, ACC, superior frontal gyrus, supplementary motor area, white matter near the hippocampus, and precentral gyrus (p < 0.05 for all). Moreover, the MCI-T group demonstrated higher metabolic activity in the default mode network (DMN) and lower activity in the executive control network (ECN) (p < 0.05 for all). In the MCI-T group, the posterior DMN was positively correlated with the visual network and negatively with the ECN, whereas in the MCI-NT group, it correlated positively with the ECN. Conclusion: The MCI-T group exhibited greater ß-amyloid accumulation in the auditory cortex and more extensive changes across various brain networks compared with the MCI-NT group, potentially leading to diverse clinical symptoms such as dementia with semantic deficits or depression. Tinnitus in MCI patients may serve as a biomarker for degenerative changes in the temporal lobe and alterations in brain network dynamics.

Toward actionable neural markers of depression risk?

The search for neural markers of depression remains challenging. Despite progress, neuroimaging results have generally not yielded actionable findings that could transform how we understand and treat this disorder. However, in a recent study, Lynch and colleagues identified enlargement of the frontrostriatal salience network as a reproducible, trait-like marker of depression.

Telehealth-delivered cognitive behavioral therapy - a potential solution to improve sleep quality and normalize the salience network in fibromyalgia: a pilot randomized trial.

Our study investigated the associations between the clinical benefits of telehealth-delivered cognitive behavioral therapy for insomnia (tele-CBT-I) and the salience network in fibromyalgia (FM). Thirty-five FM patients with comorbid insomnia were recruited and assigned into two groups: the tele-CBT-I group (n = 17) or the treatment-as-usual (TAU) group (n = 18). At baseline and post-treatment, clinical status was assessed using standardized scales, including the Insomnia Severity Index (ISI), Brief Pain Inventory, Numeric Pain Rating scale, Beck Depression Intervention version II, Beck Anxiety Intervention, Situational Fatigue Scale, and Fibromyalgia Impact Questionnaires. Resting-state functional magnetic resonance imaging was collected. We compared within- and between-group differences in clinical changes and functional connectivity (FC) of the salience network. A factor analysis of significant FCs was performed. Correlation analyses between clinical symptoms and salience FCs were conducted. The tele-CBT-I group showed sleep quality improvements after treatment that were greater than those in the TAU group (p-value = 0.038). After treatment, tele-CBT-I decreased FCs of cortical regions and increased FCs of subcortical regions compared to the TAU group. Additionally, factor analysis grouped the significant FCs into cortical factors and subcortical factors. The cortical factor value, representing the involvement of specific cortical regions of the salience network by the factor analysis, was significantly associated with ISI scores in the tele-CBT-I group (p-value = 0.0002). In conclusion, tele-CBT-I might be an adjuvant approach to improve sleep quality and normalize cortical and subcortical functions of the salience network in FM patients with comorbid insomnia.

The Brain Salience Network at the Intersection of Pain and Substance use Disorders: Insights from Functional Neuroimaging Research.

Purpose of Review: The brain's salience network (SN), primarily comprising the anterior insula and anterior cingulate cortex, plays a key role in detecting salient stimuli and processing physical and socioemotional pain (e.g., social rejection). Mounting evidence underscores an altered SN in the etiology and maintenance of substance use disorders (SUDs). This paper aims to synthesize recent functional neuroimaging research emphasizing the SN's involvement in SUDs and physical/socioemotional pain and explore the therapeutic prospects of targeting the SN for SUD treatment. Recent Findings: The SN is repeatedly activated during the experience of both physical and socioemotional pain. Altered activation within the SN is associated with both SUDs and chronic pain conditions, characterized by aberrant activity and connectivity patterns as well as structural changes. Among individuals with SUDs, functional and structural alterations in the SN have been linked to abnormal salience attribution (e.g., heightened responsiveness to drug-related cues), impaired cognitive control (e.g., impulsivity), and compromised decision-making processes. The high prevalence of physical and socioemotional pain in the SUD population may further exacerbate SN alterations, thus contributing to hindered recovery progress and treatment failure. Interventions targeting the restoration of SN functioning, such as real-time functional MRI feedback, neuromodulation, and psychotherapeutic approaches, hold promise as innovative SUD treatments. Summary: The review highlights the significance of alterations in the structure and function of the SN as potential mechanisms underlying the co-occurrence of SUDs and physical/socioemotional pain. Future work that integrates neuroimaging with other research methodologies will provide novel insights into the mechanistic role of the SN in SUDs and inform the development of next-generation treatment modalities.

Similarities and differences in dynamic properties of brain networks between internet gaming disorder and tobacco use disorder.

BACKGROUND: Internet gaming disorder (IGD) and tobacco use disorder (TUD) are two major addiction disorders that result in substantial financial loss. Identifying the similarities and differences between these two disorders is important to understand substance addiction and behavioral addiction. The current study was designed to compare these two disorders utilizing dynamic analysis. METHOD: Resting-state data were collected from 35 individuals with IGD, 35 individuals with TUD and 35 healthy controls (HCs). Dynamic coactivation pattern analysis was employed to decipher their dynamic patterns. RESULTS: IGD participants showed decreased coactivation patterns within the default mode network (DMN) and between the DMN and the salience network (SN). The SN showed reduced coactivation patterns with the executive control network (ECN) and DMN, and the ECN showed decreased coactivation patterns with the DMN. In the TUD group, the DMN exhibited decreased coactivation patterns with the SN, the SN exhibited reduced coactivation patterns with the DMN and ECN, and the ECN showed decreased coactivation patterns with the DMN and within the ECN. Furthermore, the triple network model was fitted to the dynamic properties of the two addiction disorders. Decoding analysis results indicated that addiction-related memory and memory retrieval displayed similar dysfunctions in both addictions. CONCLUSION: The dynamic characteristics of IGD and TUD suggest that there are similarities in the dynamic features between the SN and DMN and differences in the dynamic features between the DMN and ECN. Our results revealed that the two addiction disorders have dissociable brain mechanisms, indicating that future studies should consider these two addiction disorders as having two separate mechanisms to achieve precise treatment for their individualized targets.

Functional Network Connectivity for Components of Depression-Related Psychological Fragility.

Psychological resilience (PR) is known to be inversely associated with depression. While there is a growing body of research examining how depression alters activity across multiple functional neural networks, how differences in PR affect these networks is largely unexplored. This study examines the relationship between PR and functional connectivity in the alpha and beta bands within (and between) eighteen established cortical nodes in the default mode network, the central executive network, and the salience network. Resting-state EEG data from 99 adult participants (32 depressed, 67 non-depressed) were used to measure the correlation between the five factors of PR sourced from the Connor-Davidson Resilience Scale and eLORETA-based measures of coherence and phase synchronisation. Distinct functional connectivity patterns were seen across each resilience factor, with a notable absence of overlapping positive results across the depressed and non-depressed samples. These results indicate that depression may modulate how resilience is expressed in terms of fundamental neural activity.

Amygdala fMRI-A Critical Appraisal of the Extant Literature.

Even before the advent of fMRI, the amygdala occupied a central space in the affective neurosciences. Yet this amygdala-centred view on emotion processing gained even wider acceptance after the inception of fMRI in the early 1990s, a landmark that triggered a goldrush of fMRI studies targeting the amygdala in vivo. Initially, this amygdala fMRI research was mostly confined to task-activation studies measuring the magnitude of the amygdala's response to emotional stimuli. Later, interest began to shift more towards the study of the amygdala's resting-state functional connectivity and task-based psychophysiological interactions. Later still, the test-retest reliability of amygdala fMRI came under closer scrutiny, while at the same time, amygdala-based real-time fMRI neurofeedback gained widespread popularity. Each of these major subdomains of amygdala fMRI research has left its marks on the field of affective neuroscience at large. The purpose of this review is to provide a critical assessment of this literature. By integrating the insights garnered by these research branches, we aim to answer the question: What part (if any) can amygdala fMRI still play within the current landscape of affective neuroscience? Our findings show that serious questions can be raised with regard to both the reliability and validity of amygdala fMRI. These conclusions force us to cast doubt on the continued viability of amygdala fMRI as a core pilar of the affective neurosciences.

Wanting to matter and learning to care: A neurodevelopmental window of opportunity for (Pro) social learning?

Wanting to matter-to feel socially recognized, appreciated, and capable of actions that benefit others-represents a fundamental motivation in human development. The motivational salience of mattering appears to increase in adolescence. Evidence suggests this is related to pubertal increases in the incentive salience for gaining social value and personal agency. This can provide a useful heuristic for understanding motivational proclivities (i.e. wanting to matter) that influence action-outcome learning as young adolescents are exploring and learning how to navigate increasingly complex social and relational environments. Adolescence also brings new capacities, motives, and opportunities for learning to care about and contribute to the benefit of others. Together, these create a window of opportunity: a sensitive period for learning to gain salient feelings of mattering through caring prosocial actions and valued societal contributions. Successfully discovering ways of mattering by doing things that matter to others may contribute to formative socio-emotional learning about self/other. Advances in understanding these social and relational learning processes and their neurodevelopmental underpinnings can inform strategies to improve developmental trajectories of social competence and wellbeing among adolescents growing up in a rapidly changing and increasingly techno-centric world.

Salience network resting state functional connectivity during airway inflammation in asthma: A feature of mental health resilience?

BACKGROUND: Inflammation is an established contributor to the pathophysiology of depression and the prevalence of depression in those with chronic inflammatory disease is two- to four-fold higher than the general population. Yet little is known about the neurobiological changes that confer depression or resilience to depression, that occur when episodes of heightened inflammation are frequent or span many years. METHODS: We used an innovative combination of longitudinal resting state functional magnetic resonance imaging coupled to segmental bronchial provocation with allergen (SBP-Ag) to assess changes in resting state functional connectivity (rsFC) of the salience network (SN) caused by an acute inflammatory exacerbation in twenty-six adults (15 female) with asthma and varying levels of depressive symptoms. Eosinophils measured in bronchoalveolar lavage fluid and blood provided an index of allergic inflammation and the Beck Depression Inventory provided an index of depressive symptoms. RESULTS: We found that in those with the highest symptoms of depression at baseline, SN rsFC declined most from pre- to post-SBP-Ag in the context of a robust eosinophilic response to challenge, but in those with low depressive symptoms SN rsFC was maintained or increased, even in those with the most pronounced SBP-Ag response. CONCLUSIONS: Thus, the maintenance of SN rsFC during inflammation may be a biomarker of resilience to depression, perhaps via more effective orchestration of large-scale brain network dynamics by the SN. These findings advance our understanding of the functional role of the SN during inflammation and inform treatment recommendations for those with comorbid inflammatory disease and depression.

Effect of Antiseizure Medication on the Salience Network in Patients with Epilepsy with Generalized Tonic-Clonic Seizures Alone.

This study aimed to investigate the effects of antiepileptic drugs on salience network regions in patients with epilepsy with generalized tonic-clonic seizures alone (EGTCSa). A retrospective observational case-control study was performed on 40 patients diagnosed with epilepsy with EGTCSa and 40 healthy age-matched controls. In LORETA, a voxel-by-voxel analysis between regions from the salience network was performed for both hemispheres, specifically between the anterior cingulate (BA 32 and BA 24) and the sublobar insula (BA 13). Subsequently, a Wilcoxon rank-sum test (the Mann-Whitney U test) was conducted for the equality of medians in the transformation matrix. A comparison was then made between each region of interest as defined by the salience network and the controls. Marked differences were found in the brain regions assessed in patients with EGTCSa treated with valproic acid and carbamazepine compared to the control group; few differences in patients treated with levetiracetam; and no difference was found in the group without treatment compared with those in the control group. These results suggest that ASMs can influence cognitive processes, which provide novel insights toward understanding the neural mechanisms underlying the effects of ASMs administration.

Predicting Clinical Improvement in Early Psychosis Using Circuit-Based Resting-State Functional Magnetic Resonance Imaging.

BACKGROUND AND HYPOTHESIS: Identifying biomarkers that predict treatment response in early psychosis (EP) is a priority for psychiatry research. Previous work suggests that resting-state connectivity biomarkers may have promise as predictive measures, although prior results vary considerably in direction and magnitude. Here, we evaluated the relationship between intrinsic functional connectivity of the attention, default mode, and salience resting-state networks and 12-month clinical improvement in EP. STUDY DESIGN: Fifty-eight individuals with EP (less than 2 years from illness onset, 35 males, average age 20 years) had baseline and follow-up clinical data and were included in the final sample. Of these, 30 EPs showed greater than 20% improvement in Brief Psychiatric Rating Scale (BPRS) total score at follow-up and were classified as "Improvers." STUDY RESULTS: The overall logistic regression predicting Improver status was significant (χ2 = 23.66, Nagelkerke's R2 = 0.45, P < .001, with 85% concordance). Significant individual predictors of Improver status included higher default mode within-network connectivity, higher attention-default mode between-network connectivity, and higher attention-salience between-network connectivity. Including baseline BPRS as a predictor increased model significance and concordance to 92%, and the model was not significantly influenced by the dose of antipsychotic medication (chlorpromazine equivalents). Linear regression models predicting percent change in BPRS were also significant. CONCLUSIONS: Overall, these results suggest that resting-state functional magnetic resonance imaging connectivity may serve as a useful biomarker of clinical outcomes in recent-onset psychosis.

Frontoparietal and salience network synchronizations during nonsymbolic magnitude processing predict brain age and mathematical performance in youth.

The development and refinement of functional brain circuits crucial to human cognition is a continuous process that spans from childhood to adulthood. Research increasingly focuses on mapping these evolving configurations, with the aim to identify markers for functional impairments and atypical development. Among human cognitive systems, nonsymbolic magnitude representations serve as a foundational building block for future success in mathematical learning and achievement for individuals. Using task-based frontoparietal (FPN) and salience network (SN) features during nonsymbolic magnitude processing alongside machine learning algorithms, we developed a framework to construct brain age prediction models for participants aged 7-30. Our study revealed differential developmental profiles in the synchronization within and between FPN and SN networks. Specifically, we observed a linear increase in FPN connectivity, concomitant with a decline in SN connectivity across the age span. A nonlinear U-shaped trajectory in the connectivity between the FPN and SN was discerned, revealing reduced FPN-SN synchronization among adolescents compared to both pediatric and adult cohorts. Leveraging the Gradient Boosting machine learning algorithm and nested fivefold stratified cross-validation with independent training datasets, we demonstrated that functional connectivity measures of the FPN and SN nodes predict chronological age, with a correlation coefficient of .727 and a mean absolute error of 2.944 between actual and predicted ages. Notably, connectivity within the FPN emerged as the most contributing feature for age prediction. Critically, a more matured brain age estimate is associated with better arithmetic performance. Our findings shed light on the intricate developmental changes occurring in the neural networks supporting magnitude representations. We emphasize brain age estimation as a potent tool for understanding cognitive development and its relationship to mathematical abilities across the critical developmental period of youth. PRACTITIONER POINTS: This study investigated the prolonged changes in the brain's architecture across childhood, adolescence, and adulthood, with a focus on task-state frontoparietal and salience networks. Distinct developmental pathways were identified: frontoparietal synchronization strengthens consistently throughout development, while salience network connectivity diminishes with age. Furthermore, adolescents show a unique dip in connectivity between these networks. Leveraging advanced machine learning methods, we accurately predicted individuals' ages based on these brain circuits, with a more mature estimated brain age correlating with better math skills.

A connectome-based model of delusion in schizophrenia using functional connectivity under working memory task.

Delusion is an important feature of schizophrenia, which may stem from cognitive biases. Working memory (WM) is the core foundation of cognition, closely related to delusion. However, the knowledge of neural mechanisms underlying the relationship between WM and delusion in schizophrenia is poorly investigated. Two hundred and thirty patients with schizophrenia (dataset 1: n = 130; dataset 2: n = 100) were enrolled and scanned for an N-back WM task. We constructed the WM-related whole-brain functional connectome and conducted Connectome-based Predictive Modelling (CPM) to detect the delusion-related networks and built the correlation model in dataset 1. The correlation between identified networks and delusion severity was tested in a separate, heterogeneous sample of dataset 2 that mainly includes early-onset schizophrenia. The identified delusion-related network has a strong correlation with delusion severity measured by the NO.20 item of SAPS in dataset 1 (r = 0.433, p = 2.7 × 10-7, permutation-p = 0.035), and can be validated in the same dataset by using another delusion measurement, that is, the P1 item of PANSS (r = 0.362, p = 0.0005). It can be validated in another independent dataset 2 (NO.20 item of SAPS for r = 0.31, p = 0.0024, P1 item of PANSS for r = 0.27, p = 0.0074). The delusion-related network comprises the connections between the default mode network (DMN), cingulo-opercular network (CON), salience network (SN), subcortical, sensory-somatomotor network (SMN), and visual networks. We successfully established correlation models of individualized delusion based on the WM-related functional connectome and showed a strong correlation between delusion severity and connections within the DMN, CON, SMN, and subcortical network.

From brain connectivity to cognitive function: Dissecting the salience network in pediatric BECTS-ESES.

BACKGROUND: Benign childhood epilepsy with centrotemporal spikes (BECTS), a common pediatric epilepsy, may lead to cognitive decline when compounded by Electrical Status Epilepticus during Sleep (ESES). Emerging evidence suggests that disruptions in the Salience Network (SN) contribute significantly to the cognitive deficits observed in BECTS-ESES. Our study rigorously investigates the dynamic functional connectivity (dFC) within the SN and its correlation with cognitive impairments in BECTS-ESES, employing advanced neuroimaging and neuropsychological assessments. METHODS: In this research, 45 patients diagnosed with BECTS-ESES and 55 age-matched healthy controls (HCs) participated. We utilized resting-state functional magnetic resonance imaging (fMRI) and Independent Component Analysis (ICA) to identify three fundamental SN nodes: the right Anterior Insula (rAI), left Anterior Insula (lAI), and the Anterior Cingulate Cortex (ACC). A two-sample t-test facilitated the comparison of dFC between these pivotal regions and other brain areas. RESULTS: Significantly, the BECTS-ESES group demonstrated increased dFC, particularly between the ACC and the right Middle Occipital Gyrus, and from the rAI to the right Superior Parietal Gyrus and Cerebellum, and from the lAI to the left Postcentral Gyrus. Such dFC augmentations provide neural insights potentially explaining the neuropsychological deficits in BECTS-ESES children. Employing comprehensive neuropsychological evaluations, we mapped these dFC disruptions to specific cognitive impairments encompassing memory, executive functioning, language, and attention. Through multiple regression analysis and path analysis, a preliminary but compelling association was discovered linking dFC disturbances directly to cognitive impairments. These findings underscore the critical role of SN disruptions in BECTS-ESES cognitive dysfunctions. LIMITATION: Our cross-sectional design and analytic methods preclude definitive mediation models and causal inferences, leaving the precise nature of dFC's mediating role and its direct impact by BECTS-ESES partially unresolved. Future longitudinal and confirmatory studies are needed to comprehensively delineate these associations. CONCLUSION: Our study heralds dFC within the SN as a vital biomarker for cognitive impairment in pediatric epilepsy, advocating for targeted cognitive-specific interventions in managing BECTS-ESES. The preliminary nature of our findings invites further studies to substantiate these associations, offering profound implications for the prognosis and therapeutic strategies in BECTS-ESES, thereby underlining the importance of this research in the field of pediatric neurology and epilepsy management.

Brain circuits in autonomous sensory meridian response and related phenomena.

Autonomous sensory meridian response (ASMR) is characterized by a tingling sensation with a feeling of relaxation and a state of flow. We explore the neural underpinnings and comorbidities of ASMR and related phenomena with altered sensory processing. These phenomena include sensory processing sensitivity (SPS), synaesthesia, Alice in Wonderland syndrome and misophonia. The objective of this article is to uncover the shared neural substrates and distinctive features of ASMR and its counterparts. ASMR, SPS and misophonia exhibit common activations in the brain regions associated with social cognition, emotion regulation and empathy. Nevertheless, ASMR responders display reduced connectivity in the salience network (SN), while individuals with SPS exhibit increased connectivity in the SN. Furthermore, ASMR induces relaxation and temporarily reduces symptoms of depression, in contrast to SPS and misophonia, which are linked to depression. These observations lead us to propose that ASMR is a distinct phenomenon owing to its attention dispatch mechanism and its connection with emotion regulation. We suggest that increased activations in the insula, along with reduction in connectivity within the salience and default mode networks in ASMR responders, may account for their experiences of relaxation and flow states. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

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

BACKGROUND: Mindfulness 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. METHODS: The 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. RESULTS: 177 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). CONCLUSIONS: Increased 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 REGISTRATION: Name of Registry; MIND-CM study; Registration Number ClinicalTrials.gov identifier: NCT0367168; Registration Date: 14/09/2018.

The mediating role of trait impulsivity in the relation between cue-induced craving and functional connectivity within the salience network among abstinent patients with methamphetamine use disorder.

Given the widespread use and relapse of methamphetamine (METH), it has caused serious public health burdens globally. However, the neurobiological basis of METH addiction remains poorly understood. Therefore, this study aimed to use magnetic resonance imaging (MRI) to investigate changes in brain networks and their connection to impulsivity and drug craving in abstinent individuals with METH use disorder (MUDs). A total of 110 MUDs and 55 age- and gender-matched healthy controls (HCs) underwent resting-state functional MRI and T1-weighted imaging scans, and completed impulsivity and cue-induced craving measurements. We applied independent component analysis to construct functional brain networks and multivariate analysis of covariance to investigate group differences in network connectivity. Mediation analyses were conducted to explore the relationships among brain-network functional connectivity (FC), impulsivity, and drug craving in the patients. MUDs showed increased connectivity in the salience network (SN) and decreased connectivity in the default mode network compared to HCs. Impulsivity was positively correlated with FC within the SN and played a completely mediating role between METH craving and FC within the SN in MUDs. These findings suggest alterations in functional brain networks underlying METH dependence, with SN potentially acting as a core neural substrate for impulse control disorders.

Depressed patients with childhood maltreatment display altered intra- and inter-network resting state functional connectivity.

BACKGROUND: Childhood maltreatment (CM) is a major risk factor for the development of major depressive disorder (MDD). To gain more knowledge on how adverse childhood experiences influence the development of brain architecture, we studied functional connectivity (FC) alterations of neural networks of depressed patients with, or without the history of CM. METHODS: Depressed patients with severe childhood maltreatment (n = 18), MDD patients without maltreatment (n = 19), and matched healthy controls (n = 20) were examined with resting state functional MRI. History of maltreatment was assessed with the 28-item Childhood Trauma Questionnaire. Intra- and inter-network FC alterations were evaluated using FMRIB Software Library and CONN toolbox. RESULTS: We found numerous intra- and inter-network FC alterations between the maltreated and the non-maltreated patients. Intra-network FC differences were found in the default mode, visual and auditory networks, and cerebellum. Network modelling revealed several inter-network FC alterations connecting the default mode network with the executive control, salience and cerebellar networks. Increased inter-network FC was found in maltreated patients between the sensory-motor and visual, cerebellar, default mode and salience networks. LIMITATIONS: Relatively small sample size, cross-sectional design, and retrospective self-report questionnaire to assess adverse childhood experiences. CONCLUSIONS: Our findings confirm that severely maltreated depressed patients display numerous alterations of intra- and inter-network FC strengths, not only in their fronto-limbic circuits, but also in sensory-motor, visual, auditory, and cerebellar networks. These functional alterations may explain that maltreated individuals typically display altered perception and are prone to develop functional neurological symptom disorder (conversion disorder) in adulthood.