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Abstract 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

IntroductionRecent resting-state electroencephalogram (EEG) studies have consistently reported an association between aberrant functional brain networks (FBNs) and treatment-resistant traits in patients with major depressive disorder (MDD). However, little is known about the changes in FBNs in response to external stimuli in these patients. This study investigates whether changes in the salience network (SN) could predict responsiveness to pharmacological treatment in resting-state and external stimuli conditions.MethodsThirty-one drug-naïve patients with MDD (aged 46.61 ± 10.05, female 28) and twenty-one healthy controls (aged 43.86 ± 14.14, female 19) participated in the study. After 8 weeks of pharmacological treatment, the patients were divided into non-remitted MDD (nrMDD, n = 14) and remitted-MDD (rMDD, n = 17) groups. EEG data under three conditions (resting-state, standard, and deviant) were analyzed. The SN was constructed with three cortical regions as nodes and weighted phase-lag index as edges, across alpha, low-beta, high-beta, and gamma bands. A repeated measures analysis of the variance model was used to examine the group-by-condition interaction. Machine learning-based classification analyses were also conducted between the nrMDD and rMDD groups.ResultsA notable group-by-condition interaction was observed in the high-beta band between nrMDD and rMDD. Specifically, patients with nrMDD exhibited hypoconnectivity between the dorsal anterior cingulate cortex and right insula (p = 0.030). The classification analysis yielded a maximum classification accuracy of 80.65%.ConclusionOur study suggests that abnormal condition-dependent changes in the SN could serve as potential predictors of pharmacological treatment efficacy in patients with MDD.

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.

Anhedonia is a transdiagnostic clinical syndrome associated with significant clinical impairment. In spite of this, a clear network-level characterization of anhedonia does not yet exist. The present study addressed this gap in the literature by taking a graph theoretical approach to characterizing state-based (i.e., reward anticipation, rest) network dynamics in a transdiagnostic sample of adults with clinically significant anhedonia (n = 77). Analyses focused on three canonical brain networks: the Salience Network (SN), the Default Mode Network (DMN) and the Central Executive Network (CEN), with hypotheses focusing on the role of saliency-mapping in anhedonia. Contrary to hypotheses, no significant relation was found between the SN and anhedonia symptom severity. Exploratory results revealed a significant association between anhedonia severity and DMN reorganization from rest to reward anticipation. Specifically, greater anhedonia severity was associated with less reward-related reorganization. This finding suggests that anhedonia severity may be associated with DMN hyposensitivity, such that individuals with more severe anhedonia may have a difficult time disengaging from their internal world in the context of potentially rewarding experiences. Although preliminary, this finding challenges the centrality of the SN in anhedonia severity and suggests the importance of the DMN. Clinical implications and future directions are explored.

Objective: Olfactory dysfunction indicates a higher risk of developing dementia. However, the potential structural and functional changes are still largely unknown. Methods: A total of 236 participants were enrolled, including 45 Alzheimer's disease (AD) individuals and 191dementia-free individuals. Detailed study methods, comprising neuropsychological assessment and olfactory identification test (University of Pennsylvania smell identification test, UPSIT), as well as structural and functional magnetic resonance imaging (MRI) were applied in this research. The dementia-free individuals were divided into two sub-groups based on olfactory score: dementia-free with olfactory dysfunction (DF-OD) sub-group and dementia-free without olfactory dysfunction (DF-NOD) sub-group. The results were analyzed for subsequent intergroup comparisons and correlations. The cognitive assessment was conducted again three years later. Results: (i) At dementia-free stage, there was a positive correlation between olfactory score and cognitive function. (ii) In dementia-free group, the volume of crucial brain structures involved in olfactory recognition and processing (such as amygdala, entorhinal cortex and basal forebrain volumes) are positively associated with olfactory score. (iii) Compared to the DF-NOD group, the DF-OD group showed a significant reduction in olfactory network (ON) function. (iv) Compared to DF-NOD group, there were significant functional connectivity (FC) decline between PCun_L(R)_4_1 in the precuneus of posterior default mode network (pDMN) and the salience network (SN) in DF-OD group, and the FC values decreased with falling olfactory scores. Moreover, in DF-OD group, the noteworthy reduction in FC were observed between PCun_L(R)_4_1 and amygdala, which was a crucial component of ON. (v) The AD conversion rate of DF-OD was 29.41%, while the DF-NOD group was 12.50%. The structural and functional changes in the precuneus were also observed in AD and were more severe. Conclusions: In addition to the olfactory circuit, the precuneus is a critical structure in the odor identification process, whose abnormal function underlies the olfactory identification impairment of dementia-free individuals.

Abstract Background Alexithymia, a personality trait characterized by difficulties in identifying and expressing their emotions despite having a range of emotional experiences, can impact individuals’ stress coping mechanisms. While many studies have investigated brain functions associated with specific tasks in relation to emotion processing, research focusing on resting-state brain functions has been limited. Thus, the aim of this study was to investigate the relationship between alexithymia and brain function by analyzing arterial spin labeling (ASL) data obtained during the resting state. Methods A brain structural and functional imaging study was conducted on 42 healthy adult men and women using ASL and the 20-item Toronto Alexithymia Scale (TAS-20) questionnaire survey. Cerebral blood flow and functional connectivity values were calculated for regions of interest in the default mode network, saliency network, and central executive network from the ASL data. Correlation analysis was performed with TAS20 scores, and partial correlation analysis was conducted to control for anxiety and depression. Results The functional connectivity analysis revealed a negative correlation between the functional connectivity of the right insular cortex and left anterior cingulate cortex and the total score of TAS, as well as difficulty identifying feelings and difficulty describing feeling subscores, indicating that the higher the scores, the weaker the functional connectivity between these regions (T = -3.830, p = 0.0013, R = -0.5180). This correlation remained significant even after controlling for anxiety and depression using partial correlation analysis. Conclusion The present study revealed differences in the activity of the Saliency Network at rest as measured by ASL, which were independent of anxiety and depression, and varied depending on the severity of alexithymia. This functional change may underlie the neural basis of decreased emotional processing observed in alexithymia. These findings may contribute to the elucidation of the neural mechanisms of alexithymia, which can lead to social impairments, and suggest the usefulness of ASL measurement as a biomarker of alexithymia.

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.

Abstract Background Patients with remitted major depressive disorder (rMDD) show abnormal functional connectivity of the central executive network (CEN), salience networks (SN) and default mode network (DMN). It is unclear how these change during remission, or whether changes are related to function. Methods Three spatial networks in 17 patients with rMDD were compared between baseline and the six-month follow-up, and to 22 healthy controls. Correlations between these changes and psychosocial functioning were also assessed. Results In the CEN, patients at baseline had abnormal functional connectivity in the right anterior cingulate, right dorsolateral prefrontal cortex (DLPFC) and inferior parietal lobule (IPL) compare with HCs. There were functional connection differences in the right DLPFC and left IPL at baseline during follow-up. Abnormal connectivity in the right DLPFC and medial prefrontal cortex (mPFC) were found at follow-up. In the SN, patients at baseline had abnormal functional connectivity in the insula, left anterior cingulate, left IPL, and right precuneus; compared with baseline, patients had higher connectivity in the right DLPFC at follow-up. In the DMN, patients at baseline had abnormal functional connectivity in the right mPFC. Resting-state functional connectivity of the IPL and DLPFC in the CEN correlated with psychosocial functioning. Conclusions At six-month follow-up, the CEN still showed abnormal functional connectivity in those with rMDD, while anomalies in the SN and DMN has disappeared. Resting-state functional connectivity of the CEN during early rMDD is associated with psychosocial function. Clinical trials Registration Pharmacotherapy and Psychotherapy for MDD after Remission on Psychology and Neuroimaging. https://www.clinicaltrials.gov/ , registration number: NCT01831440 (15/4/2013).

Abstract Background Despite impulse control and emotion regulation being altered in borderline personality disorder (BPD), the specific mechanism of these clinical features remains unclear. This study investigated the functional connectivity (FC) abnormalities within- and between- default mode network (DMN), salience network (SN), and central executive network (CEN) in BPD, and examined the association between aberrant FC and clinical features. We aimed to explore whether the abnormal large-scale networks underlie the pathophysiology of impulsivity and emotion dysregulation in BPD. Methods Forty-one young, drug-naïve patients with BPD (24.98 ± 3.12 years, 20 males) and 42 healthy controls (HCs; 24.74 ± 1.29 years, 17 males) were included in resting-state functional magnetic resonance imaging analyses. Independent component analysis was performed to extract subnetworks of the DMN, CEN, and SN. Additionally, partial correlation was performed to explore the association between brain imaging variables and clinical features in BPD. Results Compared with HCs, BPD showed significant decreased intra-network FC of right medial prefrontal cortex in the anterior DMN and of right angular gyrus in the right CEN. Intra-network FC of right angular gyrus in the anterior DMN was significantly negatively correlated with attention impulsivity in BPD. The patients also showed decreased inter-network FC between the posterior DMN and left CEN, which was significantly negatively correlated with emotion dysregulation. Conclusion These findings suggest that impaired intra-network FC may underlie the neurophysiological mechanism of impulsivity, and abnormal inter-network FC may elucidate the neurophysiological mechanism of emotion dysregulation in BPD.

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.

Parkinson’s disease (PD) is a neurodegenerative disease with cognitive as well as motor impairments. While much is known about the brain networks leading to motor impairments in PD, less is known about the brain networks contributing to cognitive impairments. Here, we leveraged resting-state functional magnetic resonance imaging (rs-fMRI) data from the Parkinson’s Progression Marker Initiative (PPMI) to examine network dysfunction in PD patients with cognitive impairment. We focus on canonical cortical networks linked to cognition, including the salience network (SAL), frontoparietal network (FPN), and default mode network (DMN), as well as a subcortical basal ganglia network (BGN). We used the Montreal Cognitive Assessment (MoCA) as a continuous index of coarse cognitive function in PD. In 82 PD patients, we found that lower MoCA scores were linked with lower intra-network connectivity of the FPN. We also found that lower MoCA scores were linked with lower inter-network connectivity between the SAL and the BGN, the SAL and the DMN, as well as the FPN and the DMN. These data elucidate the relationship of cortical and subcortical functional connectivity with cognitive impairments in PD.

There exists a group of older individuals who appear to be resistant to age-related memory decline. These “SuperAgers” have been shown to demonstrate preservation of cortical thickness and functional connectivity strength across the cortex which positively correlates with memory performance. Over the last decade, roughly 30 articles have been published regarding SuperAgers; however, to our knowledge, no replications of these studies have been published. The current study sought to conceptually replicate Zhang and colleagues’ (2020) findings that SuperAgers demonstrate stronger intrinsic functional connectivity within the default mode (DMN) and salience networks (SN), and that connectivity strength within these networks correlates with memory performance. We identified 20 SuperAgers and 20 matched Normal Agers in the control cohort of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. We compared the functional connectivity strength of the DMN and SN between these groups, and used the Rey Auditory Verbal Learning Test (RAVLT) to evaluate correlations between functional connectivity and memory performance. Our results did not replicate Zhang and colleagues’ (2020) results, as we found negligible differences between SuperAgers and Normal Agers in the DMN and SN, and no significant correlations between functional connectivity and memory performance after accounting for multiple comparisons. More replications are needed to confirm existing work. In addition, more research with larger SuperAger samples and more consistent definitions of SuperAging is needed, so that we can better understand this remarkable group of older adults.

We consider the disorders of arousal and sleep-related hypermotor epilepsy as genetic twin-conditions, one without, one with epilepsy. They share an augmented arousal-activity during NREM sleep with sleep-wake dissociations, culminating in sleep terrors and sleep-related hypermotor seizures with similar symptoms. The known mutations underlying the two spectra are different, but there are multifold population-genetic-, family- and even individual (the two conditions occurring in the same person) overlaps supporting common genetic roots. In the episodes of disorders of arousal, the anterior cingulate, anterior insular and pre-frontal cortices (shown to be involved in fear- and emotion processing) are activated within a sleeping brain. These regions overlap with the seizure-onset zones of successfully operated sleep-related hypermotor seizures, and notably, belong to the salience network being consistent with its hubs. The arousal-relatedness and the similar fearful confusion occurring in sleep terrors and hypermotor seizures, make them alike acute stress-responses emerging from sleep; triggered by false alarms. The activation of the anterior cingulate, prefrontal and insular regions in the episodes of both conditions, can easily mobilize the hypothalamo-pituitary-adrenal axis (preparing fight-flight responses in wakefulness); through its direct pathways to and from the salience network. This hypothesis has never been studied.

Abstract Background Neuroanatomical alterations have been associated with cognitive deficits in mild traumatic brain injury (MTBI). However, most studies have focused on the abnormal gray matter volume in widespread brain regions using a cross-sectional design in MTBI. This study investigated the neuroanatomical restoration of key regions in salience network and the outcomes in MTBI. Methods Thirty-six MTBI patients with posttraumatic headache (PTH) and 34 matched healthy controls were enrolled in this study. All participants underwent magnetic resonance imaging scans and were assessed with clinical measures during the acute and subacute phases. Surface-based morphometry was conducted to get cortical thickness (CT) and cortical surface area (CSA) of neuroanatomical regions which were defined by the Desikan atlas. Then mixed analysis of variance models were performed to examine CT and CSA restoration in patients from acute to subacute phase related to controls. Finally, mediation effects models were built to explore the relationships between neuroanatomical restoration and symptomatic improvement in patients. Results MTBI patients with PTH showed reduced headache impact and improved cognitive function from the acute to subacute phase. Moreover, patients experienced restoration of CT of the left caudal anterior cingulate cortex (ACC) and left insula and cortical surface area of the right superior frontal gyrus from acute to subacute phase. Further mediation analysis found that CT restoration of the ACC and insula mediated the relationship between reduced headache impact and improved cognitive function in patients. Conclusions These results showed that neuroanatomical restoration of key regions in salience network correlated reduced headache impact with cognitive function improvement in MTBI with PTH, which further substantiated the vital role of salience network and provided an alternative clinical target for cognitive improvement in MTBI patients with PTH. Graphical Abstract

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.

ObjectiveTo investigate brain structural and functional characteristics of three brain functional networks including default mode network (DMN), central executive network (CEN), and salience network (SN) in persistent negative symptoms (PNS) patients.MethodsWe performed an activation likelihood estimation (ALE) meta-analysis of functional connectivity (FC) studies and voxel-based morphometry (VBM) studies to detect specific structural and functional alterations of brain networks between PNS patients and healthy controls.ResultsSeventeen VBM studies and twenty FC studies were included. In the DMN, PNS patients showed decreased gray matter in the bilateral medial frontal gyrus and left anterior cingulate gyrus and a significant reduction of FC in the right precuneus. Also, PNS patients had a decrease of gray matter in the left inferior parietal lobules and medial frontal gyrus, and a significant reduction of FC in the bilateral superior frontal gyrus in the CEN. In comparison with healthy controls, PNS patients exhibited reduced gray matter in the bilateral insula, anterior cingulate gyrus, left precentral gyrus and right claustrum and lower FC in these brain areas in the SN, including the left insula, claustrum, inferior frontal gyrus and extra-nuclear.ConclusionThis meta-analysis reveals brain structural and functional imaging alterations in the three networks and the interaction among these networks in PNS patients, which provides neuroscientific evidence for more personalized treatment.Systematic Review RegistrationThe PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number: CRD42022335962).

BackgroundIncreased mindfulness is associated with reduced alcohol consumption in patients with alcohol use disorder (AUD) after residential treatment. However, the underlying neurobiological mechanism of mindfulness in AUD is unclear. Therefore, we investigate the structural and functional alterations of the thalamocortical system with a focus on the mediodorsal thalamic nucleus (MD-TN), the default mode and the salience network (DMN/SN) which has previously been associated with mindfulness in healthy subjects. We hypothesized lower mindfulness and reduced structural and functional connectivity (FC) of the thalamocortical system, particularly in the DMN/SN in AUD. We assumed that identified neurobiological alterations in AUD are associated with impairments of mindfulness.MethodsForty-five abstinent patients with AUD during residential treatment and 20 healthy controls (HC) were recruited. Structural and resting-state functional MRI-scans were acquired. We analysed levels of mindfulness, thalamic volumes and network centrality degree of the MD-TN using multivariate statistics. Using seed-based whole brain analyses we investigated functional connectivity (FC) of the MD-TN. We performed exploratory correlational analyses of structural and functional DMN/SN measurements with levels of mindfulness.ResultsIn AUD we found significantly lower levels of mindfulness, lower bilateral thalamic and left MD-TN volumes, reduced FC between MD-TN and anterior cingulum/insula and lower network centrality degree of the left MD-TN as compared to HC. In AUD, lower mindfulness was associated with various reductions of structural and functional aspects of the MD-TN.ConclusionOur results suggest that structural and functional alterations of a network including the MD-TN and the DMN/SN underlies disturbed mindfulness in AUD.

Tinnitus is defined as the conscious awareness of a sound without an identifiable external sound source, and tinnitus disorder as tinnitus with associated suffering. Chronic tinnitus has been anatomically and phenomenologically separated into three pathways: a lateral “sound” pathway, a medial “suffering” pathway, and a descending noise-canceling pathway. Here, the triple network model is proposed as a unifying framework common to neuropsychiatric disorders. It proposes that abnormal interactions among three cardinal networks—the self-representational default mode network, the behavioral relevance-encoding salience network and the goal-oriented central executive network—underlie brain disorders. Tinnitus commonly leads to negative cognitive, emotional, and autonomic responses, phenomenologically expressed as tinnitus-related suffering, processed by the medial pathway. This anatomically overlaps with the salience network, encoding the behavioral relevance of the sound stimulus. Chronic tinnitus can also become associated with the self-representing default mode network and becomes an intrinsic part of the self-percept. This is likely an energy-saving evolutionary adaptation, by detaching tinnitus from sympathetic energy-consuming activity. Eventually, this can lead to functional disability by interfering with the central executive network. In conclusion, these three pathways can be extended to a triple network model explaining all tinnitus-associated comorbidities. This model paves the way for the development of individualized treatment modalities.

Abstract Introduction Several functional neuroimaging studies on healthy controls and patients with migraine with aura have shown that the activation of functional networks during visual stimulation is not restricted to the striate system, but also includes several extrastriate networks. Methods Before and after 4 min of visual stimulation with a checkerboard pattern, we collected functional MRI in 21 migraine with aura (MwA) patients and 18 healthy subjects (HS). For each recording session, we identified independent resting-state networks in each group and correlated network connection strength changes with clinical disease features. Results Before visual stimulation, we found reduced connectivity between the default mode network and the left dorsal attention system (DAS) in MwA patients compared to HS. In HS, visual stimulation increases functional connectivity between the independent components of the bilateral DAS and the executive control network (ECN). In MwA, visual stimulation significantly improved functional connectivity between the independent component pairs salience network and DAS, and between DAS and ECN. The ECN Z-scores after visual stimulation were negatively related to the monthly frequency of aura. Conclusions In individuals with MwA, 4 min of visual stimulation had stronger cognitive impact than in healthy people. A higher frequency of aura may lead to a diminished ability to obtain cognitive resources to cope with transitory but important events like aura-related focal neurological symptoms.

Conscientiousness, and related constructs impulsivity and self-control, have been related to structural and functional properties of regions in the prefrontal cortex (PFC) and anterior insula. Network-based conceptions of brain function suggest that these regions belong to a single large-scale network, labeled the salience/ventral attention network (SVAN). The current study tested associations between conscientiousness and resting-state functional connectivity in this network using two community samples (N's = 244 and 239) and data from the Human Connectome Project (N = 1000). Individualized parcellation was used to improve functional localization accuracy and facilitate replication. Functional connectivity was measured using an index of network efficiency, a graph theoretical measure quantifying the capacity for parallel information transfer within a network. Efficiency of a set of parcels in the SVAN was significantly associated with conscientiousness in all samples. Findings are consistent with a theory of conscientiousness as a function of variation in neural networks underlying effective prioritization of goals.

Core regions of the salience network (SN), including the anterior insula (aINS) and dorsal anterior cingulate cortex (dACC), coordinate rapid adaptive changes in attentional and autonomic processes in response to negative emotional events. In doing so, the SN incorporates bottom-up signals from subcortical brain regions, such as the amygdala and periaqueductal gray (PAG). However, the precise influence of these subcortical regions is not well understood. Using ultra-high field 7-Tesla functional magnetic resonance imaging, this study investigated the bottom-up interactions of the amygdala and PAG with the SN during negative emotional salience processing. Thirty-seven healthy participants completed an emotional oddball paradigm designed to elicit a salient negative emotional response via the presentation of random, task-irrelevant negative emotional images. Negative emotional processing was associated with prominent activation in the SN, spanning the amygdala, PAG, aINS, and dACC. Consistent with previous research, analysis using dynamic causal modelling revealed an excitatory influence from the amygdala to the aINS, dACC, and PAG. In contrast, the PAG showed an inhibitory influence on amygdala, aINS and dACC activity. Our findings suggest that the amygdala may amplify the processing of negative emotional stimuli in the SN to enable upstream access to attentional resources. In comparison, the inhibitory influence of the PAG possibly reflects its involvement in modulating sympathetic-parasympathetic autonomic arousal mediated by the SN. This PAG-mediated effect may be driven by amygdala input and facilitate bottom-up processing of negative emotional stimuli. Overall, our results show that the amygdala and PAG modulate divergent functions of the SN during negative emotional processing.

L’objectif principal de ce projet était d’appliquer les connaissances en neuroéducation sur les deux réseaux cérébraux, le réseau de saillance (SN) et le réseau de mode par défaut (DMN) et leur importance dans le processus d’apprentissage pour activer et maintenir l’attention et la motivation des étudiants. Suite à l'explication de comment notre cerveau fonctionne lors de l'apprentissage d'une langue seconde, les commentaires que j’ai reçus de la part des étudiants suggèrent qu'ils sont effectivement motivés à participer à mes cours. Cependant, comme il n’y a pas de rétroaction concernant l’attention, je ne peux pas en tirer des conclusions quantitatives. Une grande limite de ce projet est le questionnaire, qui était trop ouvert et n’abordait pas l’aspect de l’attention. Une autre limite de ce projet est que je ne peux pas comparer la motivation et l’attention au début et à la fin du projet. En conséquence, je ne peux pas dire si la forte motivation est effectivement due à mes méthodes d’enseignement ou à l'explication de comment le cerveau fonctionne. Enfin, le temps du projet était trop court pour tirer des conclusions significatives sur le succès des techniques d’enseignement, c’est pourquoi j’ai l’intention de poursuivre ce projet jusqu’à la fin de cette année scolaire et de répéter le questionnaire avec des questions plus précises les années à venir.

Abstract There are many neuroimaging studies of mild behavioral impairment (MBI), but the results have been somewhat inconsistent. Moreover, it remains unclear whether MBI is a risk factor or prodromal symptom of dementia. Therefore, a systematic review was conducted to summarize the results of neuroimaging studies of MBI and consider whether MBI is a prodromal symptom of dementia in terms of its neural correlates. A systematic review supported by a JSPS Grant‐in‐Aid for Scientific Research (C) was conducted using MBI neuroimaging studies identified using PubMed, PsycINFO, CINAHL, and Google Scholar on November 1, 2022. The inclusion criteria were (i) neuroimaging study; (ii) research on human subjects; (iii) papers written in English; and (iv) not a case study, review, book, comments, or abstract only. Joanna Briggs Institute critical appraisal checklists were used to assess the quality of selected studies, and 23 structural and functional imaging studies were ultimately included in the systematic review. The structural studies suggested an association of MBI with atrophy in the hippocampus, parahippocampal gyrus, entorhinal cortex, and temporal lobe, whereas the functional studies indicated involvement of an altered default mode network, frontoparietal control network, and salience network in MBI. A limitation in many studies was the use of region‐of‐interest analysis. The brain areas detected as neural correlates of MBI are considered to be alterations in the early stage of each dementia. Therefore, MBI may emerge against a background of pathological changes in dementia.

Non-invasive brain stimulation is designed to target accessible brain regions that underlie many psychiatric disorders. One such method, transcranial magnetic stimulation (TMS), is commonly used in patients with treatment-resistant depression (TRD). However, for non-responders, the choice of an alternative therapy is unclear and often decided empirically without detailed knowledge of precise circuit dysfunction. This is also true of invasive therapies, such as deep brain stimulation (DBS), in which responses in TRD patients are linked to circuit activity that varies in each individual. If the functional networks affected by these approaches were better understood, a theoretical basis for selection of interventions could be developed to guide psychiatric treatment pathways. The mechanistic understanding of TMS is that it promotes long-term potentiation of cortical targets, such as dorsolateral prefrontal cortex (DLPFC), which are attenuated in depression. DLPFC is highly interconnected with other networks related to mood and cognition, thus TMS likely alters activity remote from DLPFC, such as in the central executive, salience and default mode networks. When deeper structures such as subcallosal cingulate cortex (SCC) are targeted using DBS for TRD, response efficacy has depended on proximity to white matter pathways that similarly engage emotion regulation and reward. Many have begun to question whether these networks, targeted by different modalities, overlap or are, in fact, the same. A major goal of current functional and structural imaging in patients with TRD is to elucidate neuromodulatory effects on the aforementioned networks so that treatment of intractable psychiatric conditions may become more predictable and targeted using the optimal technique with fewer iterations. Here, we describe several therapeutic approaches to TRD and review clinical studies of functional imaging and tractography that identify the diverse loci of modulation. We discuss differentiating factors associated with responders and non-responders to these stimulation modalities, with a focus on mechanisms of action for non-invasive and intracranial stimulation modalities. We advance the hypothesis that non-invasive and invasive neuromodulation approaches for TRD are likely impacting shared networks and critical nodes important for alleviating symptoms associated with this disorder. We close by describing a therapeutic framework that leverages personalized connectome-guided target identification for a stepwise neuromodulation paradigm.

Abstract Background Pituitary adenoma (PA) may compress the optic apparatus, resulting in impaired vision. Some patients can experience improved vision rapidly after surgery. During the early period after surgery, however, the change in neurofunction in the extravisual cortex and higher cognitive cortex has yet to be explored. Objective Our study focused on the changes in the extravisual resting-state networks in patients with PA after vision restoration. Methods We recruited 14 patients with PA who experienced visual improvement after surgery. The functional connectivity (FC) of 6 seeds [auditory cortex (A1), Broca’s area, posterior cingulate cortex (PCC) for the default mode network (DMN), right caudal anterior cingulate cortex for the salience network (SN) and left dorsolateral prefrontal cortex for the executive control network (ECN)] were evaluated. A paired t test was conducted to identify the differences between two groups of patients. Results Compared with their preoperative counterparts, patients with PA with improved vision exhibited decreased FC with the right A1 in the left insula lobule, right middle temporal gyrus and left postcentral gyrus and increased FC in the right paracentral lobule; decreased FC with the Broca in the left middle temporal gyrus and increased FC in the left insula lobule and right thalamus; decreased FC with the DMN in the right declive and right precuneus; increased FC in right Brodmann area 17, the left cuneus and the right posterior cingulate; decreased FC with the ECN in the right posterior cingulate, right angular and right precuneus; decreased FC with the SN in the right middle temporal gyrus, right hippocampus, and right precuneus; and increased FC in the right fusiform gyrus, the left lingual gyrus and right Brodmann area 19. Conclusions Vision restoration may cause a response of cross-modal plasticity and multisensory systems related to A1 and the Broca. The DMN and SN may be involved in top-down control of the subareas within the visual cortex. The precuneus may be involved in the DMN, ECN and SN simultaneously.

Group forming behaviors are common in many species to overcome environmental challenges. In humans, bonding, trust, group norms, and a shared past increase consolidation of social groups. Being a part of a social group increases resilience to mental stress; conversely, its loss increases vulnerability to depression. However, our knowledge on how social group support affects brain functions is limited. This study observed that default mode network (DMN) activity reduced with the loss of social group support from real-life friends in a challenging social competition. The loss of support induced anterior temporoparietal activity followed by anterior insula and the dorsal attentional network activity. Being a part of a social group and having support provides an environment for high cognitive functioning of the DMN, while the loss of group support acts as a threat signal and activates the anterior temporoparietal junction (TPJ) and insula regions of salience and attentional networks for individual survival.

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.

BackgroundThis study aimed to investigate the relationships between regional neural activity and multiple related indicators in patients with major depressive disorder (MDD).MethodsForty-two patients and 42 healthy controls (HCs) were enrolled. Pearson/Spearman correlation analyses were applied to examine the associations between abnormal regional homogeneity (ReHo) and different indicators in the patients.ResultsCompared with HCs, patients with MDD had increased ReHo in the left inferior temporal gyrus (ITG) and decreased ReHo values in the left putamen, anterior cingulate cortex (ACC), and precentral gyrus. The ReHo of the left putamen was positively correlated with the PR interval, Repeatable Battery for the Assessment of Neuropsychological Status 4A, and Discriminant analysis (D), and negatively correlated with Ae (block) and Ae (total) in the patients. The ReHo value of the left ACC was positively correlated with the severity of depression, Stroop Color Word Test of C − 2B + 100 in reaction time, and negatively correlated with Ce (Missay) and Perseverative Responses in the patients. The ReHo of the left ITG was positively correlated with the Neuroticism scores and negatively correlated with the Lie scores in the patients.ConclusionThese results suggested that the decreased ReHo of the salience network might be the underpinning of cognitive impairments in patients with MDD.

Enhanced emotional empathy, the ability to share others’ affective experiences, can be a feature of Alzheimer’s disease (AD), but whether emotional empathy increases in the preclinical phase of the disease is unknown. We measured emotional empathy over time (range = 0 – 7.3 years, mean = 2.4 years) in 86 older adults during a period in which they were cognitively healthy, functionally normal, and free of dementia symptoms. For each participant, we computed longitudinal trajectories for empathic concern (i.e., an other-oriented form of emotional empathy that promotes prosocial actions) and emotional contagion (i.e., a self-focused form of emotional empathy often accompanied by feelings of distress) from informant ratings of participants’ empathy on the Interpersonal Reactivity Index. Amyloid-β (Aβ) positron emission tomography (PET) scans were used to classify participants as either Aβ positive (Aβ+, n = 23) or negative (Aβ-, n = 63) based on Aβ-PET cortical binding. Participants also underwent structural and task-free functional magnetic resonance imaging approximately two years on average after their last empathy assessment, at which time most participants remained cognitively healthy. Results indicated that empathic concern, but not emotional contagion, increased more over time in Aβ+ participants than in Aβ- participants despite no initial group difference at the first measurement. Higher connectivity between certain salience network node-pairs (i.e., pregenual anterior cingulate cortex and periaqueductal gray) predicted longitudinal increases in empathic concern in the Aβ+ group but not in the Aβ- group. The Aβ+ participants also had higher overall salience network connectivity than Aβ- participants despite no differences in gray matter volume. These results suggest gains in empathic concern may be a very early feature of AD pathophysiology that relates to hyperconnectivity in the salience network, a system that supports emotion generation and interoception. A better understanding of emotional empathy trajectories in the early stages of AD pathophysiology will broaden the lens on preclinical AD changes and help clinicians to identify older adults who should be screened for AD biomarkers.

Abstract Background Medication-overuse headache (MOH) is a relatively frequently occurring secondary headache caused by overuse of analgesics and/or acute migraine medications. It is believed that MOH is associated with dependence behaviors and substance addiction, in which the salience network (SN) and the habenula may play an important role. This study aims to investigate the resting-state (RS) functional connectivity between the habenula and the SN in patients with MOH complicating chronic migraine (CM) compared with those with episodic migraine (EM) and healthy controls (HC). Methods RS-fMRI and 3-dimensional T1-weighted images of 17 patients with MOH + CM, 18 patients with EM and 30 matched healthy HC were obtained. The RS-fMRI data were analyzed using the independent component analysis (ICA) method to investigate the group differences of functional connectivity between the habenula and the SN in three groups. Correlation analysis was performed thereafter with all clinical variables by Pearson correlation. Results Increased functional connectivity between bilateral habenula and SN was detected in patients with MOH + CM compared with patients with EM and HC respectively. Correlation analysis showed significant correlation between medication overuse duration and habenula-SN connectivity in MOH + CM patients. Conclusions The current study supported MOH to be lying within a spectrum of dependence and addiction disorder. The enhanced functional connectivity of the habenula with SN may correlate to the development or chronification of MOH. Furthermore, the habenula may be an indicator or treatment target for MOH for its integrative role involved in multiple aspects of MOH.

Background: Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation whose potential as a cognitive therapy is hindered by our limited understanding of how participant and experimental factors influence its effects. Using functional MRI to study brain networks, we have previously shown in healthy controls that the physiological effects of tDCS are strongly influenced by brain state. We have additionally shown, in both healthy and traumatic brain injury (TBI) populations, that the behavioral effects of tDCS are positively correlated with white matter (WM) structure. Objectives: In this study we investigate how these two factors, WM structure and brain state, interact to shape the effect of tDCS on brain network activity. Methods: We applied anodal, cathodal and sham tDCS to the right inferior frontal gyrus (rIFG) of healthy (n = 22) and TBI participants (n = 34). We used the Choice Reaction Task (CRT) performance to manipulate brain state during tDCS. We acquired simultaneous fMRI to assess activity of cognitive brain networks and used Fractional Anisotropy (FA) as a measure of WM structure. Results: We find that the effects of tDCS on brain network activity in TBI participants are highly dependent on brain state, replicating findings from our previous healthy control study in a separate, patient cohort. We then show that WM structure further modulates the brain-state dependent effects of tDCS on brain network activity. These effects are not unidirectional - in the absence of task with anodal and cathodal tDCS, FA is positively correlated with brain activity in several regions of the default mode network. Conversely, with cathodal tDCS during CRT performance, FA is negatively correlated with brain activity in a salience network region. Conclusions: Our results show that experimental and participant factors interact to have unexpected effects on brain network activity, and that these effects are not fully predictable by studying the factors in isolation.

Understanding the neural basis for individual differences in the skin conductance response (SCR) during discriminative fear conditioning may inform on our understanding of autonomic regulation in fear-related psychopathology. Previous region-of-interest (ROI) analyses have implicated the amygdala in regulating conditioned SCR, but whole brain analyses are lacking. This study examined correlations between individual differences in SCR during discriminative fear conditioning to social stimuli and neural activity throughout the brain, by using data from a large functional magnetic resonance imaging study of twins (N = 285 individuals). Results show that conditioned SCR correlates with activity in the dorsal anterior cingulate cortex/anterior midcingulate cortex, anterior insula, bilateral temporoparietal junction, right frontal operculum, bilateral dorsal premotor cortex, right superior parietal lobe, and midbrain. A ROI analysis additionally showed a positive correlation between amygdala activity and conditioned SCR in line with previous reports. We suggest that the observed whole brain correlates of SCR belong to a large-scale midcingulo-insular network related to salience detection and autonomic-interoceptive processing. Altered activity within this network may underlie individual differences in conditioned SCR and autonomic aspects of psychopathology.

Tinnitus can be defined as the conscious perception of phantom sounds in the absence of corresponding external auditory signals. Tinnitus can develop in the setting of sudden sensorineural hearing loss (SSNHL), but the underlying mechanism is largely unknown. Using electroencephalography, we investigated differences in afferent node capacity between 15 SSNHL patients without tinnitus (NT) and 30 SSNHL patients with tinnitus (T). Where the T group showed increased afferent node capacity in regions constituting a “triple brain network” [default mode network (DMN), central executive network (CEN), and salience network (SN)], the NT group showed increased information flow in regions implicated in temporal auditory processing and noise-canceling pathways. Our results demonstrate that when all components of the triple network are activated due to sudden-onset auditory deprivation, tinnitus ensues. By contrast, auditory processing-associated and tinnitus-suppressing networks are highly activated in the NT group, to overcome the activation of the triple network and effectively suppress the generation of tinnitus.

Cognitive complaints of attention/concentration problems are highly frequent in older adults with subjective cognitive decline (SCD). Functional connectivity in the cingulo-opercular network (CON-FC) supports cognitive control, tonic alertness, and visual processing speed. Thus, those complaints in SCD may reflect a decrease in CON-FC. Frontal white-matter tracts such as the forceps minor exhibit age- and SCD-related alterations and, therefore, might influence the CON-FC decrease in SCD. Here, we aimed to determine whether SCD predicts an impairment in CON-FC and whether neurite density in the forceps minor modulates that effect. To do so, we integrated cross-sectional and longitudinal analyses of multimodal data in a latent growth curve modeling approach. Sixty-nine healthy older adults (13 males; 68.33 ± 7.95 years old) underwent resting-state functional and diffusion-weighted magnetic resonance imaging, and the degree of SCD was assessed at baseline with the memory functioning questionnaire (greater score indicating more SCD). Forty-nine of the participants were further enrolled in two follow-ups, each about 18 months apart. Baseline SCD did not predict CON-FC after three years or its rate of change (p-values > 0.092). Notably, however, the forceps minor neurite density did modulate the relation between SCD and CON-FC (intercept; b = 0.21, 95% confidence interval, CI, [0.03, 0.39], p = 0.021), so that SCD predicted a greater CON-FC decrease in older adults with relatively lower neurite density in the forceps minor. The neurite density of the forceps minor, in turn, negatively correlated with age. These results suggest that CON-FC alterations in SCD are dependent upon the forceps minor neurite density. Accordingly, these results imply modifiable age-related factors that could help delay or mitigate both age and SCD-related effects on brain connectivity.

Prominent theories propose that interoception modulates our behavioral and emotional responses involving decision-making and emotion regulation. Are the regions implicated in interoception also spatially related to and possibly nested within the networks of decision making and emotion regulation? Addressing this question, we performed three meta-analyses of functional magnetic resonance imaging studies to identify the regions that are commonly activated by the three domains using activation likelihood estimation (ALE). Additionally, we assessed the coactivation pattern of identified common regions using meta-analytic connectivity modeling (MACM). The results showed major overlaps of interoception with both decision making and emotion regulation in specifically the right dorsal anterior insula. The pairwise contrast analyses confirmed this finding and revealed conjunction-based activities in decision making and emotion regulation in the dorsal anterior cingulate cortex (dACC). MACM based on the identified insula revealed a widespread convergent coactivation pattern with the left anterior insula, dACC, and bilateral thalamus which, together, constitute the salience network. Among these co-activated regions, bilateral insula and the dACC were shared among all three domains. These results suggest that the regions mediating interoception including intero-exteroceptive integration and salience attribution are contained and thus spatially nested within the more extensive networks recruited during decision making and emotion regulation.

BackgroundNumerous resting-state studies on attention deficit hyperactivity disorder (ADHD) have reported aberrant functional connectivity (FC) between the default-mode network (DMN) and the ventral attention/salience network (VA/SN). This finding has commonly been interpreted as an index of poorer DMN regulation associated with symptoms of mind wandering in ADHD literature. However, a competing perspective suggests that dysfunctional organization of the DMN and VA/SN may additionally index increased sensitivity to the external environment. The goal of the current study was to test this latter perspective in relation to auditory distraction by investigating whether ADHD-adults exhibit aberrant FC between DMN, VA/SN, and auditory networks.MethodsTwelve minutes of resting-state fMRI data was collected from two adult groups: ADHD (n = 17) and controls (n = 17); from which the FC between predefined regions comprising the DMN, VA/SN, and auditory networks were analyzed.ResultsA weaker anticorrelation between the VA/SN and DMN was observed in ADHD. DMN and VA/SN hubs also exhibited aberrant FC with the auditory network in ADHD. Additionally, participants who displayed a stronger anticorrelation between the VA/SN and auditory network at rest, also performed better on a cognitively demanding behavioral task that involved ignoring a distracting auditory stimulus.ConclusionResults are consistent with the hypothesis that auditory distraction in ADHD is linked to aberrant interactions between DMN, VA/SN, and auditory systems. Our findings support models that implicate dysfunctional organization of the DMN and VA/SN in the disorder and encourage more research into sensory interactions with these major networks.

Methylphenidate is a widely used first-line treatment for attention deficit/hyperactivity disorder (ADHD), but the underlying circuit mechanisms are poorly understood. Here we investigate whether a single dose of osmotic release oral system methylphenidate can remediate attention deficits and aberrancies in functional circuit dynamics in cognitive control networks, which have been implicated in ADHD. In a randomized placebo-controlled double-blind crossover design, 27 children with ADHD were scanned twice with resting-state functional MRI and sustained attention was examined using a continuous performance task under methylphenidate and placebo conditions; 49 matched typically-developing (TD) children were scanned once for comparison. Dynamic time-varying cross-network interactions between the salience (SN), frontoparietal (FPN), and default mode (DMN) networks were examined in children with ADHD under both administration conditions and compared with TD children. Methylphenidate improved sustained attention on a continuous performance task in children with ADHD, when compared to the placebo condition. Children with ADHD under placebo showed aberrancies in dynamic time-varying cross-network interactions between the SN, FPN and DMN, which were remediated by methylphenidate. Multivariate classification analysis confirmed that methylphenidate remediates aberrant dynamic brain network interactions. Furthermore, dynamic time-varying network interactions under placebo conditions predicted individual differences in methylphenidate-induced improvements in sustained attention in children with ADHD. These findings suggest that a single dose of methylphenidate can remediate deficits in sustained attention and aberrant brain circuit dynamics in cognitive control circuits in children with ADHD. Findings identify a novel brain circuit mechanism underlying a first-line pharmacological treatment for ADHD, and may inform clinically useful biomarkers for evaluating treatment outcomes.

Abstract Background The salience network (SN) is a transitory mediator between active and passive states of mind. Multiple cortical areas, including the opercular, insular, and cingulate cortices have been linked in this processing, though knowledge of network connectivity has been devoid of structural specificity. Objective The current study sought to create an anatomically specific connectivity model of the neural substrates involved in the salience network. Methods A literature search of PubMed and BrainMap Sleuth was conducted for resting‐state and task‐based fMRI studies relevant to the salience network according to PRISMA guidelines. Publicly available meta‐analytic software was utilized to extract relevant fMRI data for the creation of an activation likelihood estimation (ALE) map and relevant parcellations from the human connectome project overlapping with the ALE data were identified for inclusion in our SN model. DSI‐based fiber tractography was then performed on publicaly available data from healthy subjects to determine the structural connections between cortical parcellations comprising the network. Results Nine cortical regions were found to comprise the salience network: areas AVI (anterior ventral insula), MI (middle insula), FOP4 (frontal operculum 4), FOP5 (frontal operculum 5), a24pr (anterior 24 prime), a32pr (anterior 32 prime), p32pr (posterior 32 prime), and SCEF (supplementary and cingulate eye field), and 46. The frontal aslant tract was found to connect the opercular‐insular cluster to the middle cingulate clusters of the network, while mostly short U‐fibers connected adjacent nodes of the network. Conclusion Here we provide an anatomically specific connectivity model of the neural substrates involved in the salience network. These results may serve as an empiric basis for clinical translation in this region and for future study which seeks to expand our understanding of how specific neural substrates are involved in salience processing and guide subsequent human behavior.

Growing evidence supports a role of the neuropeptide oxytocin in promoting social cognition and prosocial behavior, possibly via modulation of the salience of social information. The effect of intranasal oxytocin administration on the salience network, however, is not well understood, including in the aging brain. To address this research gap, 42 young (22.52 ± 3.02 years; 24 in the oxytocin group) and 43 older (71.12 ± 5.25 years; 21 in the oxytocin group) participants were randomized to either self-administer intranasal oxytocin or placebo prior to resting-state functional imaging. The salience network was identified using independent component analysis (ICA). Independent t-tests showed that individuals in the oxytocin compared to the placebo group had lower within-network resting-state functional connectivity, both for left amygdala (MNI coordinates: x = -18, y = 0, z = -15; corrected p < 0.05) within a more ventral salience network and for right insula (MNI coordinates: x = 39, y = 6, z = -6; corrected p < 0.05) within a more dorsal salience network. Age moderation analysis furthermore demonstrated that the oxytocin-reduced functional connectivity between the ventral salience network and the left amygdala was only present in older participants. These findings suggest a modulatory role of exogenous oxytocin on resting-state functional connectivity within the salience network and support age-differential effects of acute intranasal oxytocin administration on this network.

The data show an association between measured and predicted changes in cognitive performance in older adults who are cognitively normal. Changes in cognitive performance over two years were assessed using the Cognitive Composite Score. The prediction of change in cognitive function was based on changes in pairwise functional connectivity between 80 gray matter regions examined by resting-state functional magnetic resonance imaging. A feature extraction process based on the Variable Importance Testing Approach (VITA) identified changes in 11 pairs of functional connections associated with the default mode network as features related to changes in cognitive performance. Linear and elastic net regression models were applied to these 11 features to predict changes in cognitive performance over two years. A relationship between the 11 features and the geriatric depression score was also shown. The dataset supplements the research findings in the ''Changes in pairwise functional connectivity associated with changes in cognitive performance in cognitively normal older individuals: a two-year observational study'' published in Oishi et al. (2022). The raw rs-fMRI correlation matrix and associated clinical data can be accessed upon request from the BIOCARD website (www.biocard-se.org) and can be reused for predictive model building.

Human neuroimaging has demonstrated the existence of large-scale functional networks in the cerebral cortex consisting of topographically distant brain regions with functionally correlated activity. The salience network (SN), which is involved in detecting salient stimuli and mediating inter-network communication, is a crucial functional network that is disrupted in addiction. Individuals with addiction display dysfunctional structural and functional connectivity of the SN. Furthermore, while there is a growing body of evidence regarding the SN, addiction, and the relationship between the two, there are still many unknowns, and there are fundamental limitations to human neuroimaging studies. At the same time, advances in molecular and systems neuroscience techniques allow researchers to manipulate neural circuits in nonhuman animals with increasing precision. Here, we describe attempts to translate human functional networks to nonhuman animals to uncover circuit-level mechanisms. To do this, we review the structural and functional connections of the salience network and its homology across species. We then describe the existing literature in which circuit-specific perturbation of the SN sheds light on how functional cortical networks operate, both within and outside the context of addiction. Finally, we highlight key outstanding opportunities for mechanistic studies of the SN.

Background: An estimated 99 in 100,000 people experience a traumatic brain injury (TBI), with 85% being mild (mTBI) in nature. The Post-Concussion Symptom Scale (PCSS), is a reliable and valid measure of post-mTBI symptoms; however, diagnostic specificity is challenging due to high symptom rates in the general population. Understanding the neurobiological characteristics that distinguish high and low PCSS raters may provide further clarification on this phenomenon. Aim: To explore the neurobiological characteristics of post-concussion symptoms through the association between PCSS scores, brain network connectivity (using quantitative electroencephalography; qEEG) and cognition in undergraduates. Hypotheses: high PCSS scorers will have (1) more network dysregulation and (2) more cognitive dysfunction compared to the low PCSS scorers. Methods: A sample of 40 undergraduates were divided into high and low PCSS scorers. Brain connectivity was measured using qEEG, and cognition was measured via neuropsychological measures of sustained attention, inhibition, immediate attention, working memory, processing speed and inhibition/switching. Results: Contrary to expectations, greater frontoparietal network dysregulation was seen in the low PCSS score group (p = 0.003). No significant difference in cognitive dysfunction was detected between high and low PCSS scorers. Post-hoc analysis in participants who had experienced mTBI revealed greater network dysregulation in those reporting a more recent mTBI. Conclusions: Measuring post-concussion symptoms alone is not necessarily informative about changes in underlying neural mechanisms. In an exploratory subset analysis, brain network dysregulation appears to be greater in the early post-injury phase compared to later. Further analysis of underlying PCSS constructs and how to measure these in a non-athlete population and clinical samples is warranted.

Cognitive impairments are commonly observed in patients with multiple sclerosis and are associated with lower levels of quality of life. No consensus has been reached on how to tackle effectively cognitive decline in this clinical population non-pharmacologically. This exploratory case-control study aims to investigate the effectiveness of a hypothesis-based cognitive training designed to target multiple domains by promoting the synchronous co-activation of different brain areas and thereby improve cognition and induce changes in functional connectivity in patients with relapsing-remitting multiple sclerosis. Forty-five patients (36 females and 9 males, mean age 44.62 ± 8.80 years) with clinically stable relapsing-remitting multiple sclerosis were assigned to either a standard cognitive training or to control groups (sham training and non-active control). The standard training included twenty sessions of computerized exercises involving various cognitive functions supported by distinct brain networks. The sham training was a modified version of the standard training that comprised the same exercises and number of sessions but with increased processing speed load. The non-active control group received no cognitive training. All patients underwent comprehensive neuropsychological and magnetic resonance imaging assessments at baseline and after 5 weeks. Cognitive and resting-state magnetic resonance imaging data were analyzed using repeated measures models. At reassessment, the standard training group showed significant cognitive improvements compared to both control groups in memory tasks not specifically targeted by the training: the Buschke Selective Reminding Test and the Semantic Fluency test. The standard training group showed reductions in functional connectivity of the salience network, in the anterior cingulate cortex, associated with improvements on the Buschke Selective Reminding Test. No changes were observed in the sham training group. These findings suggest that multi-domain training that stimulates multiple brain areas synchronously may improve cognition in people with relapsing-remitting multiple sclerosis if sufficient time to process training material is allowed. The associated reduction in functional connectivity of the salience network suggests that training-induced neuroplastic functional reorganization may be the mechanism supporting performance gains. This study was approved by the Regional Ethics Committee of Yorkshire and Humber (approval No. 12/YH/0474) on November 20, 2013.

Alcohol use disorder (AUD) continues to be challenging to treat despite the best available interventions, with two-thirds of individuals going on to relapse by 1 year after treatment. Recent advances in the brain-based conceptual framework of addiction have allowed the field to pivot into a neuromodulation approach to intervention for these devastative disorders. Small trials of repetitive transcranial magnetic stimulation (rTMS) have used protocols developed for other psychiatric conditions and applied them to those with addiction with modest efficacy. Recent evidence suggests that a TMS approach focused on modulating the salience network (SN), a circuit at the crossroads of large-scale networks associated with AUD, may be a fruitful therapeutic strategy. The anterior insula or dorsal anterior cingulate cortex may be particularly effective stimulation sites given emerging evidence of their roles in processes associated with relapse.

ObjectMajor depressive disorder (MDD) has been demonstrated to be associated with abnormalities in neural networks. However, few studies examined information flow in the salience network (SN). This study examined abnormalities in the causal connectivity between the SN and whole brain in drug-naive first-episode patients with MDD in the resting state.MethodsBased on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria, 23 drug-naive first-episode MDD patients and 20 matched healthy individuals were recruited and underwent a resting-state magnetic resonance scan. The acquired functional image data were preprocessed using resting-state functional magnetic resonance imaging (rs-fMRI) data analysis toolkit plus (RESTplus). Then, using the data processing & analysis for brain imaging (DPABI) software and a coefficient-based general component analysis method with the right anterior insula (rAI) as the region of interest (ROI), the causal connectivity of the SN with the whole brain and its correlation with cognitive and mental performance were examined in the resting state.Results(1) The MDD group showed a significantly higher Hamilton Depression Rating Scale total score and significantly higher scores for anxiety, cognitive disturbance, and block factors compared with normal controls. (2) Compared with control: from whole brain to the rAI, the MDD group showed a lower causal connectivity in the left inferior frontal gyrus; from the rAI to the whole brain, the MDD group showed a lower causal connectivity in the right cingulate gyrus, the right precuneus, and extending to paracentral lobule but higher causal connectivity in the left inferior and middle frontal gyrus. (3) In the MDD group, from rAI to the whole brain, the causal connectivity values for the right cingulate gyrus/precuneus were negatively correlated with the score of Stroop Color-Word Test A, B, and C as well as interference times.ConclusionOur results indicated disrupted causal connectivity among the default mode network (DMN), the central executive network (CEN), and SN in drug-naive first-episode MDD patients. Especially, our results suggest a unique role for rAI in the ordered or hierarchical information processing, presumed to include bottom-up and top-down reciprocal influences among the three networks in MDD.

Abstract Background There are gaps in our neurobiological understanding of functional movement disorder (FMD). Objectives We investigated gray matter volumetric profiles in FMD, and related findings to resting‐state functional connectivity (rsFC) profiles using Human Connectome Project data. Methods Volumetric differences between 53 FMD patients and 50 controls were examined, as well as relationships between individual differences in FMD symptom severity and volumetric profiles. Atrophy network mapping was also used to probe whether FMD‐related structural alterations preferentially impacted brain areas with dense rsFC. Results Compared to controls without neurological comorbidities (albeit with mild depression and anxiety as a group), the FMD cohort did not show any volumetric differences. Across patients with FMD, individual differences in symptom severity negatively correlated with right supramarginal and bilateral superior temporal gyri volumes. These findings remained significant adjusting for FMD subtype or antidepressant use, but did not remain statistically significant adjusting for depression and anxiety scores. Symptom severity‐related structural alterations mapped onto regions with dense rsFC—identifying several disease epicenters in default mode, ventral attention, and salience networks. Conclusions This study supports that FMD is a multinetwork disorder with an important role for the temporoparietal junction and its related connectivity in the pathophysiology of this condition. More research is needed to explore the intersection of functional neurological symptoms and mood.

Neuroimaging techniques have advanced our knowledge about neurobiological mechanisms of reward and emotion processing. It remains unclear whether reward and emotion-related processing share the same neural connection topology and how intrinsic brain functional connectivity organization changes to support emotion- and reward-related prioritized effects in decision-making. The present study addressed these challenges using a large-scale neural network analysis approach. We applied this approach to two independent functional magnetic resonance imaging datasets, where participants performed a reward value or emotion associative matching task with tight control over experimental conditions. The results revealed that interaction between the Default Mode Network, Frontoparietal, Dorsal Attention, and Salience networks engaged distinct topological structures to support the effects of reward, positive and negative emotion processing. Detailed insights into the properties of these connections are important for understanding in detail how the brain responds in the presence of emotion and reward related stimuli. We discuss the linking of reward- and emotion-related processing to emotional regulation, an important aspect of regulation of human behavior in relation to mental health.

BackgroundThe central executive network (CEN), salience network (SN), and default mode network (DMN) are the three most studied depression-related brain networks. Many studies have shown that they are related to depression symptoms and treatment effects. However, few studies have related these three networks and their activity frequency bands to depressive symptoms and treatment efficacy.MethodsSixty-six medication-free patients with major depressive disorder (MDD) were enrolled. Magnetoencephalography (MEG) was administered at baseline to calculate imaging indicators such as the power and functional connectivity (FC) of each brain network. The Hamilton Rating Score for Depression (HRSD-17) was assessed at baseline and weekly for 4 weeks. Pearson correlation and receiver operating characteristic curves (ROC) analyses were used to explore the relationship between brain imaging indicators and antidepressant efficacy.ResultsThe difference between therapeutically effective and ineffective groups was mainly manifested in the beta power of the SN. The FC of beta waves between the three networks was related to antidepressant efficacy, with ROC analysis results of AUC = 0.794, P = 0.004, sensitivity = 76.7%, and specificity = 81.8%.LimitationsThe sample size was small and a healthy control group was not available.ConclusionsThe interaction between the three networks is related to antidepressant efficacy and the relief of depressive symptoms.

According to the inhibition deficit hypothesis, the ability to inhibit unwanted or irrelevant thoughts and behaviors decreases with age, which can have a significant impact on cognitive and emotional processing. However, studies examining inhibition and age have shown mixed results, with some studies finding a decrease in inhibitory control as individuals age, while others have found no relationship. The goal of this proof-of-concept study was to examine the underlying neural mechanisms that may explain why some older adults are better than others at inhibitory control by investigating the relationship between resting-state functional connectivity (rsFC) of the salience network, a network critical for detecting and focusing attention toward relevant stimuli while ignoring irrelevant information in the environment, and a behavioral measure of inhibitory control (Stroop Task interference score) in a sample of 65 healthy older individuals (ages 65+). Results revealed no direct effect of age on Stroop performance; however, there was an indirect effect of age on Stroop performance through rsFC. These results suggest that rsFC of the salience network may be an important factor to consider when it comes to understanding individual differences in inhibitory control behavior among older adults.