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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.

BACKGROUND: Fetal exposure to maternal mood dysregulation influences child cognitive and emotional development, which may have long-lasting implications for mental health. However, the neurobiological alterations associated with this dimension of adversity have yet to be explored. Here, we tested the hypothesis that fetal exposure to entropy, a novel index of dysregulated maternal mood, would predict the integrity of the salience network, which is involved in emotional processing. METHODS: A sample of 138 child-mother pairs (70 females) participated in this prospective longitudinal study. Maternal negative mood level and entropy (an index of variable and unpredictable mood) were assessed 5 times during pregnancy. Adolescents engaged in a functional magnetic resonance imaging task that was acquired between 2 resting-state scans. Changes in network integrity were analyzed using mixed-effect and latent growth curve models. The amplitude of low frequency fluctuations was analyzed to corroborate findings. RESULTS: Prenatal maternal mood entropy, but not mood level, was associated with salience network integrity. Both prenatal negative mood level and entropy were associated with the amplitude of low frequency fluctuations of the salience network. Latent class analysis yielded 2 profiles based on changes in network integrity across all functional magnetic resonance imaging sequences. The profile that exhibited little variation in network connectivity (i.e., inflexibility) consisted of adolescents who were exposed to higher negative maternal mood levels and more entropy. CONCLUSIONS: These findings suggest that fetal exposure to maternal mood dysregulation is associated with a weakened and inflexible salience network. More broadly, they identify maternal mood entropy as a novel marker of early adversity that exhibits long-lasting associations with offspring brain development.

Introduction: Recent 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. Methods: Thirty-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. Results: A notable group-by-condition interaction was observed in the highbeta 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%. Conclusion: Our study suggests that abnormal condition-dependent changes in the SN could serve as potential predictors of pharmacological treatment efficacy in patients with MDD. [ABSTRACT FROM AUTHOR]

The concept of the self is complex and there is no consensus on what the self is. However, there are emerging patterns in the literature that point to two different selves, the narrative and experiential self. The narrative self refers to a conceptual or representational knowledge of the self that extends across time and manifests in self-reflection and personality assessments. The experiential self refers to firstperson perception, moment-to-moment awareness, embodiment, and a sense of agency. These two selves are reliably linked to two distinct neural circuits, the default mode network (DMN) and the insula and salience network (SN). One of the consistent themes in the meditative and mindfulness literature is a change in the perspective of the self. In this paper, I will review how meditation alters those neural circuits providing a plausible mechanism that can explain the changes in the self. I also propose a rudimentary conceptual framework to account for some of the mixed results found throughout meditation literature. [ABSTRACT FROM AUTHOR]

Background: Although numerous studies have shown that bariatric surgery results in sustained weight loss and modifications in gut microbiota composition and cognitive function, the exact underlying mechanisms are unclear. This study aimed to investigate the effects of bariatric surgery on cognitive function through the microbiota-gut-brain axis (MGBA). Methods: Demographic data, serum samples, fecal samples, cognitive assessment scales, and resting-state functional connectivity magnetic resonance imaging (rs-fMRI) scans were obtained from 39 obese patients before and after (6 months) laparoscopic sleeve gastrectomy (LSG). PCA analysis, OPLS-DA analysis, and permutation tests were used to conduct fecal 16 S microbiota profiling, serum metabolomics, and neuroimaging analyses, and a bariatric surgery-specific rs-fMRI brain functional connectivity network was constructed. Spearman correlation analysis and Co-inertia analysis were employed to correlate significant alterations in cognitive assessment scales and resting-state functional connectivity difference networks with differential serum metabolites and 16 S microbiota data to identify key gut microbiota and serum metabolic factors. Results: LSG significantly reduced the weight of obese patients, with reductions of up to 28%. Furthermore, cognitive assessment scale measurements revealed that LSG enhanced cognitive functions, including memory (HVLT, p = 0.000) and executive function (SCWT, p = 0.008). Also, LSG significantly altered gut microbiota composition (p = 0.001), with increased microbial abundance and diversity (p < 0.05). Moreover, serum metabolite levels were significantly altered, revealing intergroup differences in 229 metabolites mapped to 72 metabolic pathways (p < 0.05, VIP > 1). Spearman correlation analysis among cognitive assessment scales, gut microbiota species, and serum metabolites revealed correlations with 68 gut microbiota species and 138 serum metabolites (p < 0.05). Furthermore, pairwise correlations were detected between gut microbiota and serum metabolites (p < 0.05). Functional neuroimaging analysis revealed that LSG increased functional connectivity in cognitive-related frontotemporal networks (FPN, p < 0.01). Additionally, normalization of the default mode network (DMN) and salience network (SN) connectivity was observed after LSG (p < 0.001). Further canonical correlation and correlation analysis suggested that the cognitive-related brain network changes induced by LSG were associated with key gut microbiota species (Akkermansia, Blautia, Collinsella, Phascolarctobacterium, and Ruminococcus, p < 0.05) and neuroactive metabolites (Glycine, L-Serine, DL-Dopa, SM (d18:1/24:1(15Z), p < 0.05). Conclusion: These findings indicate the pathophysiological role of the microbiota-gut-brain axis in enhancing cognitive function after bariatric surgery, and the study provides a basis for clinical dietary adjustments, probiotic supplementation, and guidance for bariatric surgery, but further research is still needed. Trial registration: Chinese Clinical Trial Registry, ChiCTR2100049403. Registered 02 August 2021, https://www.chictr.org.cn/. [ABSTRACT FROM AUTHOR]

Cortical cholinergic projections originate from subregions of the basal forebrain (BF). To examine its organization in humans, we computed multimodal gradients of BF connectivity by combining 7 T diffusion and resting state functional MRI. Moving from anteromedial to posterolateral BF, we observe reduced tethering between structural and functional connectivity gradients, with the lowest tethering in the nucleus basalis of Meynert. In the neocortex, this gradient is expressed by progressively reduced tethering from unimodal sensory to transmodal cortex, with the lowest tethering in the midcingulo-insular network, and is also spatially correlated with the molecular concentration of VAChT, measured by [18F]fluoroethoxy-benzovesamicol (FEOBV) PET. In mice, viral tracing of BF cholinergic projections and [18F]FEOBV PET confirm a gradient of axonal arborization. Altogether, our findings reveal that BF cholinergic neurons vary in their branch complexity, with certain subpopulations exhibiting greater modularity and others greater diffusivity in the functional integration with their cortical targets. The basal forebrain innervates the cortex with cholinergic projections via long-range branching projections. Using MRI and PET, the authors show that these projections exhibit gradients of increasing branch complexity traversing unimodal to transmodal cortex. [ABSTRACT FROM AUTHOR]

Background: Individuals using methamphetamine (METH) may experience psychosis, which usually requires aggressive treatment. Studies of the neural correlates of METH-associated psychosis (MAP) have focused predominantly on the default mode network (DMN) and cognitive control networks. We hypothesize that METH use alters global functional connections in resting-state brain networks and that certain cross-network connections could be associated with psychosis. Methods: We recruited 24 healthy controls (CRL) and 54 men with METH use disorder (MUD) who were then divided into 25 without psychosis (MNP) and 29 with MAP. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), evaluating (1) large-scale alterations in regional-wise resting-state functional connectivity (rsFC) across 11 brain networks and (2) associations between rsFC and psychotic symptom severity. Results: The MUD group exhibited greater rsFC between the salience network (SN)-DMN, and subcortical network (SCN)-DMN compared to the CRL group. The MAP group exhibited decreased rsFC in the sensory/somatomotor network (SMN)-dorsal attention network (DAN), SMN-ventral attention network (VAN), SMN-SN, and SMN-auditory network (AN), whereas the MNP group exhibited increased rsFC in the SMN-DMN and the frontoparietal network (FPN)-DMN compared to CRL. Additionally, the MAP group exhibited decreased rsFC strength between the SMN-DMN, SMN-AN, SMN-FPN, and DMN-VAN compared to the MNP group. Furthermore, across the entire MUD group, the PANSS-Positive subscale was negatively correlated with the DMN-FPN and FPN-SMN, while the PANSS-Negative subscale was negatively correlated with the DMN-AN and SMN-SMN. Conclusion: MUD is associated with altered global functional connectivity. In addition, the MAP group exhibits a different brain functional network compared to the MNP group. [ABSTRACT FROM AUTHOR]

Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), and pica, are psychobehavioral conditions characterized by abnormal eating behaviors and an excessive preoccupation with weight and body shape. This review examines changes in brain regions and functional connectivity in ED patients over the past decade (2013–2023) using resting-state functional magnetic resonance imaging (rs-fMRI). Key findings highlight alterations in brain networks such as the default mode network (DMN), central executive network (CEN), and emotion regulation network (ERN). In individuals with AN, there is reduced functional connectivity in areas associated with facial information processing and social cognition, alongside increased connectivity in regions linked to sensory stimulation, aesthetic judgment, and social anxiety. Conversely, BED patients show diminished connectivity in the dorsal anterior cingulate cortex within the salience network and increased connectivity in the posterior cingulate cortex and medial prefrontal cortex within the DMN. These findings suggest that rs-fMRI could serve as a valuable biomarker for assessing brain function and predicting treatment outcomes in EDs, paving the way for personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Objective: Research indicates that cognitive control is compromised in individuals with internet gaming disorder (IGD). However, the neural mechanisms behind it are still unclear. This study aims to investigate alterations in resting-state brain networks in adolescents with IGD and the potential neurobiological mechanisms underlying cognitive dysfunction. Materials and methods: A total of 44 adolescent IGD subjects (male/female: 38/ 6) and 50 healthy controls (male/female: 40/10) were enrolled. Participants underwent demographic assessments, Young's Internet Addiction Scale, Barratt Impulsiveness Scale 11 Chinese Revised Version, the Chinese Adolescents' Maladaptive Cognitions Scale, exploratory eye movement tests, and functional magnetic resonance imaging (fMRI). FMRI data were analyzed using the GIFT software for independent component analysis, focusing on functional connectivity within and between resting-state brain networks. Results: In comparison to the control group, impulsivity in adolescent IGD subjects showed a positive correlation with the severity of IGD (r=0.6350, p < 0.001), linked to impairments in the Executive Control Network (ECN) and a decrease in functional connectivity between the Salience Network (SN) and ECN (r=0.4307, p=0.0021; r=-0.5147, p=0.0034). Decreased resting state activity of the dorsal attention network (DAN) was associated with attentional dysregulation of IGD in adolescents (r=0.4071, p=0.0017), and ECN increased functional connectivity with DAN. The degree of IGD was positively correlated with enhanced functional connectivity between the ECN and DAN (r=0.4283, p=0.0037). Conclusions: This research demonstrates that changes in the ECN and DAN correlate with heightened impulsivity and attentional deficits in adolescents with IGD. The interaction between cognitive control disorders and resting-state brain networks in adolescent IGD is related. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the neural mechanisms that differentiate mind--body practices from aerobic physical activities and elucidate their effects on cognition and healthy aging. We examined functional brain connectivity in older adults (age > 60) without pre-existing uncontrolled chronic diseases, comparing Tai Chi with Water Aerobics practitioners. Methods: We conducted a cross-sectional, case--control fMRI study involving two strictly matched groups (n = 32) based on gender, age, education, and years of practice. Seed-to-voxel analysis was performed using the Salience, and Frontoparietal Networks as seed regions in Stroop Word-Color and N-Back tasks and Resting State. Results: During Resting State condition and using Salience network as a seed, Tai Chi group exhibited a stronger correlation between Anterior Cingulate Cortex and Insular Cortex areas (regions related to interoceptive awareness, cognitive control and motor organization of subjective aspects of experience). In N-Back task and using Salience network as seed, Tai Chi group showed increased correlation between Left Supramarginal Gyrus and various cerebellar regions (related to memory, attention, cognitive processing, sensorimotor control and cognitive flexibility). In Stroop task, using Salience network as seed, Tai Chi group showed enhanced correlation between Left Rostral Prefrontal Cortex and Right Occipital Pole, and Right Lateral Occipital Cortex (areas associated with sustained attention, prospective memory, mediate attention between external stimuli and internal intention). Additionally, in Stroop task, using Frontoparietal network as seed, Water Aerobics group exhibited a stronger correlation between Left Posterior Parietal Lobe (specialized in word meaning, representing motor actions, motor planning directed to objects, and general perception) and different cerebellar regions (linked to object mirroring). Conclusion: Our study provides evidence of differences in functional connectivity between older adults who have received training in a mind--body practice (Tai Chi) or in an aerobic physical activity (Water Aerobics) when performing attentional and working memory tasks, as well as during resting state. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Atypical social impairments (i.e., impaired social cognition and social communication) are vital manifestations of autism spectrum disorder (ASD) patients, and the incidence rate of ASD is significantly higher in males than in females. Characterizing the atypical brain patterns underlying social deficits of ASD is significant for understanding the pathogenesis. However, there are no robust imaging biomarkers that are specific to ASD, which may be due to neurobiological complexity and limitations of single‐modality research. To describe the multimodal brain patterns related to social deficits in ASD, we highlighted the potential functional role of white matter (WM) and incorporated WM functional activity and gray matter structure into multimodal fusion. Gray matter volume (GMV) and fractional amplitude of low‐frequency fluctuations of WM (WM‐fALFF) were combined by fusion analysis model adopting the social behavior. Our results revealed multimodal spatial patterns associated with Social Responsiveness Scale multiple scores in ASD. Specifically, GMV exhibited a consistent brain pattern, in which salience network and limbic system were commonly identified associated with all multiple social impairments. More divergent brain patterns in WM‐fALFF were explored, suggesting that WM functional activity is more sensitive to ASD's complex social impairments. Moreover, brain regions related to social impairment may be potentially interconnected across modalities. Cross‐site validation established the repeatability of our results. Our research findings contribute to understanding the neural mechanisms underlying social disorders in ASD and affirm the feasibility of identifying biomarkers from functional activity in WM. [ABSTRACT FROM AUTHOR]

The identification of a neurodegenerative disorders distributed pattern of atrophy-or atrophy signature-can lend insights into the cortical networks that degenerate in individuals with specific constellations of symptoms. In addition, this signature can be used as a biomarker to support early diagnoses and to potentially reveal pathological changes associated with said disorder. Here, we characterized the cortical atrophy signature of behavioural variant frontotemporal dementia (bvFTD). We used a data-driven approach to estimate cortical thickness using surface-based analyses in two independent, sporadic bvFTD samples (n = 30 and n = 71, total n = 101), using age- and gender-matched cognitively and behaviourally normal individuals. We found highly similar patterns of cortical atrophy across the two independent samples, supporting the reliability of our bvFTD signature. Next, we investigated whether our bvFTD signature targets specific large-scale cortical networks, as is the case for other neurodegenerative disorders. We specifically asked whether the bvFTD signature topographically overlaps with the salience network, as previous reports have suggested. We hypothesized that because phenotypic presentations of bvFTD are diverse, this would not be the case, and that the signature would cross canonical network boundaries. Consistent with our hypothesis, the bvFTD signature spanned rostral portions of multiple networks, including the default mode, limbic, frontoparietal control and salience networks. We then tested whether the signature comprised multiple anatomical subtypes, which themselves overlapped with specific networks. To explore this, we performed a hierarchical clustering analysis. This yielded three clusters, only one of which extensively overlapped with a canonical network (the limbic network). Taken together, these findings argue against the hypothesis that the salience network is preferentially affected in bvFTD, but rather suggest that-at least in patients who meet diagnostic criteria for the full-blown syndrome-neurodegeneration in bvFTD encompasses a distributed set of prefrontal, insular and anterior temporal nodes of multiple large-scale brain networks, in keeping with the phenotypic diversity of this disorder.

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

Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely utilized to investigate plasticity mechanisms and functional reorganization in multiple sclerosis (MS). Among many resting state (RS) networks, a significant role is played by the salience network (SN, ventral attention network). Previous reports have demonstrated the involvement of osteopontin (OPN) in the pathogenesis of MS, which acts as a proinflammatory cytokine ultimately leading to neurodegeneration. Concentration of serum OPN was related to MRI findings 10.22±2.84 years later in 44 patients with MS. Local and interhemispheric correlations (LCOR, IHC), ROI-to-ROI and seed-based connectivity analyses were performed using serum OPN levels as independent variable along with age and gender as nuisance variables. We found significant associations between OPN levels and local correlation in right and left clusters encompassing the central opercular- and insular cortices (p-FDR = 0.0018 and p-FDR = 0.0205, respectively). Moreover, a significant association was identified between OPN concentration and interhemispheric correlation between central opercular- and insular cortices (p-FDR = 0.00015). Significant positive associations were found between OPN concentration and functional connectivity (FC) within the SN (FC strength between the anterior insula ventral division and 3 other insular regions, F(2,13) = 7.84, p-FDR = 0.0117). Seed-based connectivity analysis using the seven nodes of the SN resulted in several positive and inverse associations with OPN level. Serum OPN level may predict FC alterations within the SN in 10 years. [ABSTRACT FROM AUTHOR]

To investigate changes in brain network organization and possible neurobehavioral similarities to attention-deficit hyperactivity disorder (ADHD), we measured changes in brain resting-state functional connectivity (rs-fMRI) and cognitive domains in patients with resistance to thyroid hormone β (RTHβ) and compared them with those in healthy control subjects. In this prospective case-control study, twenty-one participants with genetically confirmed RTHβ were matched with 21 healthy controls. The Adult ADHD Self-Report Scale (ASRS-v1.1) and ADHD Rating Scale-IV were used to assess self-reported symptoms of ADHD. A voxel-wise and atlas-based approach was used to identify changes in the brain networks. The RTHβ group reported behavioral symptoms similar to those of ADHD. We found evidence of weaker network integration of the lingual and fusiform gyri in the RTHβ group, which was mainly driven by weaker connectivity to the bilateral insula and supplementary motor cortex. Functional connectivity between regions of the default mode network (angular gyrus/middle temporal gyrus) and regions of the cognitive control network (bilateral middle frontal gyrus) was increased in RTHβ patients compared to healthy controls. Increased connectivity between regions of the default mode network and the dorsolateral prefrontal cortex is frequently reported in ADHD and is interpreted to be associated with deficits in attention. Our finding of weaker connectivity of the lingual gyrus to the bilateral insula (salience network) in RTHβ patients has also been reported previously in ADHD and may reflect decreased habituation to visual stimuli and increased distractibility. Overall, our observations support the notion of neuropsychological similarities between RTHβ and ADHD. [ABSTRACT FROM AUTHOR]

Background: The neuropathologic mechanism of primary insomnia (PI) of females remains unclear. This study aims to investigate the features of amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in females with PI using functional magnetic resonance imaging (fMRI), and then explore the abnormalities of functional connectivity (FC). Materials and methods: A total of 39 female PI patients and 31 female healthy controls (HC) were enrolled in the study. The sleep condition was assessed using the Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI), and their depressive symptom was evaluated using the Hamilton Depression Scale (HAMD-24). The rs-fMRI was once conducted for every subject. ReHo, ALFF, and ROI-based FC were used to analyze the changes of brain function. Results: ALFF values were increased in the Cerebelum_4_5_L, as well as decreased ALFF in the bilateral Frontal_Sup_Medial (SFGmed), Angular_L (ANG.L), Parietal_ Inf_R (IPL.R), SupraMarginal_R (SMG.R), and Postcentral_R (PoCG.R). ReHo values were increased in the Temporal_Pole_Mid_R (TPOsup.R), as well as decreased ReHo in the Insula_R (INS.R), Frontal_Inf_Oper_R (ORBinf.R), Putamen_R (PUT.R), Rolandic_Oper_R (ROL.R), bilateral Cingulum_Post (PCG), bilateral Frontal_Sup_ Medial (SFGmed), bilateral anterior cingulate and paracingulate gyri (ACG), and the bilateral precuneus (PCUN). Across the entire brain, there was a decline in the FC between Angular_R and Frontal_Sup_Medial_L. Conclusion: Alterations in brain regions of female patients with PI involved multiple functional networks, including the default mode network, the salience network, the central executive network, and the limbic network. Reduced coordination between functional networks may be an important mechanism for insomnia and may lead to reduced cognitive function and decision-making ability. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Attention lapses (ALs) are complete lapses of responsiveness in which performance is briefly but completely disrupted and during which, as opposed to microsleeps, the eyes remain open. Although the phenomenon of ALs has been investigated by behavioural and physiological means, the underlying cause of an AL has largely remained elusive. This study aimed to investigate the underlying physiological substrates of behaviourally identified endogenous ALs during a continuous visuomotor task, primarily to answer the question: Were the ALs during this task due to extreme mind‐wandering or mind‐blanks? The data from two studies were combined, resulting in data from 40 healthy non‐sleep‐deprived subjects (20M/20F; mean age 27.1 years, 20–45). Only 17 of the 40 subjects were used in the analysis due to a need for a minimum of two ALs per subject. Subjects performed a random 2‐D continuous visuomotor tracking task for 50 and 20 min in Studies 1 and 2, respectively. Tracking performance, eye‐video, and functional magnetic resonance imaging (fMRI) were recorded simultaneously. A human expert visually inspected the tracking performance and eye‐video recordings to identify and categorise lapses of responsiveness as microsleeps or ALs. Changes in neural activity during 85 ALs (17 subjects) relative to responsive tracking were estimated by whole‐brain voxel‐wise fMRI and by haemodynamic response (HR) analysis in regions of interest (ROIs) from seven key networks to reveal the neural signature of ALs. Changes in functional connectivity (FC) within and between the key ROIs were also estimated. Networks explored were the default mode network, dorsal attention network, frontoparietal network, sensorimotor network, salience network, visual network, and working memory network. Voxel‐wise analysis revealed a significant increase in blood‐oxygen‐level‐dependent activity in the overlapping dorsal anterior cingulate cortex and supplementary motor area region but no significant decreases in activity; the increased activity is considered to represent a recovery‐of‐responsiveness process following an AL. This increased activity was also seen in the HR of the corresponding ROI. Importantly, HR analysis revealed no trend of increased activity in the posterior cingulate of the default mode network, which has been repeatedly demonstrated to be a strong biomarker of mind‐wandering. FC analysis showed decoupling of external attention, which supports the involuntary nature of ALs, in addition to the neural recovery processes. Other findings were a decrease in HR in the frontoparietal network before the onset of ALs, and a decrease in FC between default mode network and working memory network. These findings converge to our conclusion that the ALs observed during our task were involuntary mind‐blanks. This is further supported behaviourally by the short duration of the ALs (mean 1.7 s), which is considered too brief to be instances of extreme mind‐wandering. This is the first study to demonstrate that at least the majority of complete losses of responsiveness on a continuous visuomotor task are, if not due to microsleeps, due to involuntary mind‐blanks. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Schizophrenia is accompanied by aberrant interactions of intrinsic brain networks. However, the modulatory effect of electroencephalography (EEG) rhythms on the functional connectivity (FC) in schizophrenia remains unclear. This study aims to provide new insight into network communication in schizophrenia by integrating FC and EEG rhythm information. After collecting simultaneous resting-state EEG-functional magnetic resonance imaging data, the effect of rhythm modulations on FC was explored using what we term "dynamic rhythm information." We also investigated the synergistic relationships among three networks under rhythm modulation conditions, where this relationship presents the coupling between two brain networks with other networks as the center by the rhythm modulation. This study found FC between the thalamus and cortical network regions was rhythm-specific. Further, the effects of the thalamus on the default mode network (DMN) and salience network (SN) were less similar under alpha rhythm modulation in schizophrenia patients than in controls (m e a n S c Z : m e a n H C = 0. 7 1 5 : 0. 7 7 7). However, the similarity between the effects of the central executive network (CEN) on the DMN and SN under gamma modulation was greater (m e a n S c Z : m e a n H C = 0. 6 9 5 : 0. 6 2 9), and the degree of coupling was negatively correlated with the duration of disease (r = − 0. 3 7 3 , p = 0. 0 0 3). Moreover, schizophrenia patients exhibited less coupling with the thalamus as the center and greater coupling with the CEN as the center. These results indicate that modulations in dynamic rhythms might contribute to the disordered functional interactions seen in schizophrenia. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Introduction: Although memory challenges in autistic individuals have been characterized recently, the functional connectivity of the hippocampus and ventral temporal lobe, two structures important for episodic and semantic memory functions, are poorly understood in autistic individuals. Moreover, agerelated differences in the functional connectivity associated with these two memory networks are unrevealed. Methods: The current study investigated age-related differences in intrinsic connectivity of the hippocampal and ventral temporal lobe (vTL) memory networks in well-matched ASD (n = 73; age range: 10.23-55.40 years old) and Non-ASD groups (n = 74; age range: 10.46-56.20 years old) from the open dataset ABIDE-I. Both theory-driven ROI-to-ROI approach and exploratory seed-based whole-brain approach were used. Results and discussion: Our findings revealed reduced connectivity in ASD compared to Non-ASD peers, as well as an age-related reduction in the connectivity of hippocampal and vTL networks with triple networks, namely, the default mode network (DMN), the central executive network (CEN), and the salience network (SN), potentially underpinning their challenges in memory, language, and social functions. However, we did not observe reliable differences in age-related effects between the ASD and Non-ASD groups. Our study underscores the importance of understanding memory network dysfunctions in ASD across the lifespan to inform educational and clinical practices. [ABSTRACT FROM AUTHOR]

Visual processing relies on the identification of both local and global features of visual stimuli. While well investigated at the behavioral level, the underlying brain mechanisms are less clear, especially in the context of aging. Using fMRI, we aimed to investigate the neural correlates underlying local and global processing in early and late adulthood. We recruited 77 healthy adults aged 19–77 who completed a visual search task based on 2-level hierarchical stimuli made of squares and/or circles. Participants were instructed to detect a target (a square) at either a local (small) or global (large) level of a hierarchical geometrical form, in the presence or absence of other hierarchical geometrical forms (distractors). At the behavioral level, we revealed high accuracy for all participants, but older participants were slower to detect local targets, specifically in presence of distractors. At the brain level, while both local and global processing were associated with occipital activation, local processing also recruited the anterior insula and dorsal anterior cingulate cortex, that are core regions of the salience network. However, while the presence of distractors in the local condition elicited specifically stronger activation within the right anterior insula for the young group, it was not observed for older participants. In addition, older participants showed less activation than younger participants in the occipital cortex, especially for the most complex conditions. Our findings suggest that the brain correlates underlying local and global processing change with aging, especially for complex visual patterns. These results are discussed in terms of top-down reduction effects from the salience network on primary visual areas, that may lead to specific difficulties to process local visual details in older adults. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

The agonist–antagonist myoneural interface (AMI) is an amputation surgery that preserves sensorimotor signaling mechanisms of the central-peripheral nervous systems. Our first neuroimaging study investigating AMI subjects conducted by Srinivasan et al. (2020) focused on task-based neural signatures, and showed evidence of proprioceptive feedback to the central nervous system. The study of resting state neural activity helps non-invasively characterize the neural patterns that prime task response. In this study on resting state functional magnetic resonance imaging in AMI subjects, we compared functional connectivity in patients with transtibial AMI (n = 12) and traditional (n = 7) amputations (TA). To test our hypothesis that we would find significant neurophysiological differences between AMI and TA subjects, we performed a whole-brain exploratory analysis to identify a seed region; namely, we conducted ANOVA, followed by t-test statistics to locate a seed in the salience network. Then, we implemented a seed-based connectivity analysis to gather cluster-level inferences contrasting our subject groups. We show evidence supporting our hypothesis that the AMI surgery induces functional network reorganization resulting in a neural configuration that significantly differs from the neural configuration after TA surgery. AMI subjects show significantly less coupling with regions functionally dedicated to selecting where to focus attention when it comes to salient stimuli. Our findings provide researchers and clinicians with a critical mechanistic understanding of the effect of AMI amputation on brain networks at rest, which has promising implications for improved neurorehabilitation and prosthetic control. [ABSTRACT FROM AUTHOR]

When a single choice impacts on life outcomes, faculties to make ethical judgments come into play. Here we studied decisions in a real-life setting involving life-and-death outcomes that affect others and the decision-maker as well. We chose a genuine situation where prior training and expertise play a role: firefighting in life-threatening situations. By studying the neural correlates of dilemmas involving life-saving decisions, using realistic firefighting situations, allowed us to go beyond previously used hypothetical dilemmas, while addressing the role of expertise and the use of coping strategies (n = 47). We asked the question whether the neural underpinnings of deontologically based decisions are affected by expertise. These realistic life-saving dilemmas activate the same core reward and affective processing network, in particular the ventromedial prefrontal cortex, nucleus accumbens and amygdala, irrespective of prior expertise, thereby supporting general domain theories of ethical decision-making. We found that brain activity in the hippocampus and insula parametrically increased as the risk increased. Connectivity analysis showed a larger directed influence of the insula on circuits related to action selection in non-experts, which were slower than experts in non rescuing decisions. Relative neural activity related to the decision to rescue or not, in the caudate nucleus, insula and anterior cingulate cortex was negatively associated with coping strategies, in experts (firefighters) suggesting practice-based learning. This shows an association between activity and expert-related usage of coping strategies. Expertise enables salience network activation as a function of behavioural coping dimensions, with a distinct connectivity profile when facing life-rescuing dilemmas. [ABSTRACT FROM AUTHOR]

Objective: Recent research has highlighted the insula as a critical hub in human brain networks and the most susceptible region to subjective cognitive decline (SCD). However, the changes in functional connectivity of insular subregions in SCD patients remain poorly understood. The present study aims to clarify the altered functional connectivity patterns within insular subregions in individuals with SCD using resting-state functional magnetic resonance imaging (rs-fMRI). Methods: In this study, we collected rs-fMRI data from 30 patients with SCD and 28 healthy controls (HCs). By defining three subregions of the insula, we mapped whole-brain resting-state functional connectivity (RSFC). We identified several distinct RSFC patterns of the insular subregions. Specifically, for positive connectivity, three cognitive-related RSFC patterns were identified within the insula, suggesting anterior-to-posterior functional subdivisions: (1) a dorsal anterior zone of the insula that shows RSFC with the executive control network (ECN); (2) a ventral anterior zone of the insula that shows functional connectivity with the salience network (SN); and (3) a posterior zone along the insula that shows functional connectivity with the sensorimotor network (SMN). Results: Compared to the controls, patients with SCD exhibited increased positive RSFC to the sub-region of the insula, demonstrating compensatory plasticity. Furthermore, these abnormal insular subregion RSFCs are closely correlated with cognitive performance in the SCD patients. Conclusion: Our findings suggest that different insular subregions exhibit distinct patterns of RSFC with various functional networks, which are affected differently in patients with SCD. [ABSTRACT FROM AUTHOR]

Background: Theoretical and empirical evidence indicates the critical role of the default mode network (DMN) in the pathophysiology of the bipolar disorder (BD). This study aims to identify the specific brain regions of the DMN that is impaired in patients with BD. Methods: A total of 56 patients with BD and 71 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Three commonly used functional indices, i.e., fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC), were utilized to identify the brain region showing abnormal spontaneous brain activity in patients with BD. Then, this region served as the seed region for resting-state functional connectivity (rsFC) analysis. Results: Compared to the HC group, the BD group showed reduced fALFF, ReHo, and DC values in the left precuneus. Moreover, patients exhibited decreased rsFCs within the left precuneus and between the left precuneus and the medial prefrontal cortex. Additionally, there was diminished negative connectivity between the left precuneus and the left putamen, extending to the left insula (putamen/insula). The abnormalities in DMN functional connectivity were confirmed through various analysis strategies. Conclusions: Our findings provide convergent evidence for the abnormalities in the DMN, particularly located in the left precuneus. Decreased functional connectivity within the DMN and the reduced anticorrelation between the DMN and the salience network are found in patients with BD. These findings suggest that the DMN is a key aspect for understanding the neural basis of BD, and the altered functional patterns of DMN may be a potential candidate biomarker for diagnosis of BD. [ABSTRACT FROM AUTHOR]

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.

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.

Introduction: Aberrant brain functional connectivity network is thought to be related to cognitive impairment in patients with type 2 diabetes mellitus (T2DM). This study aims to investigate the triple-network effective connectivity patterns in patients with T2DM within and between the default mode network (DMN), salience network (SN), and executive control network (ECN) and their associations with cognitive declines. Methods: In total, 92 patients with T2DM and 98 matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Spectral dynamic causal modeling (spDCM) was used for effective connectivity analysis within the triple network. The posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), lateral prefrontal cortex (LPFC), supramarginal gyrus (SMG), and anterior insula (AINS) were selected as the regions of interest. Group comparisons were performed for effective connectivity calculated using the fully connected model, and the relationships between effective connectivity alterations and cognitive impairment as well as clinical parameters were detected. Results: Compared to HCs, patients with T2DM exhibited increased or decreased effective connectivity patterns within the triple network. Furthermore, diabetes duration was significantly negatively correlated with increased effective connectivity from the r-LPFC to the mPFC, while body mass index (BMI) was significantly positively correlated with increased effective connectivity from the l-LPFC to the l-AINS (r = − 0.353, p = 0.001; r = 0.377, p = 0.004). Conclusion: These results indicate abnormal effective connectivity patterns within the triple network model in patients with T2DM and provide new insight into the neurological mechanisms of T2DM and related cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Converging evidence implicates disrupted brain connectivity in autism spectrum disorder (ASD); however, the mechanisms linking altered connectivity early in development to the emergence of ASD symptomatology remain poorly understood. Here we examined whether atypicalities in the Salience Network – an early-emerging neural network involved in orienting attention to the most salient aspects of one's internal and external environment – may predict the development of ASD symptoms such as reduced social attention and atypical sensory processing. Six-week-old infants at high likelihood of developing ASD based on family history exhibited stronger Salience Network connectivity with sensorimotor regions; infants at typical likelihood of developing ASD demonstrated stronger Salience Network connectivity with prefrontal regions involved in social attention. Infants with higher connectivity with sensorimotor regions had lower connectivity with prefrontal regions, suggesting a direct tradeoff between attention to basic sensory versus socially-relevant information. Early alterations in Salience Network connectivity predicted subsequent ASD symptomatology, providing a plausible mechanistic account for the unfolding of atypical developmental trajectories associated with vulnerability to ASD. Infants with heightened vs. lower likelihood of developing autism spectrum disorder exhibit different functional connectivity patterns in the salience network. These patterns predict sensory and social behaviors at 1 year of age. [ABSTRACT FROM AUTHOR]

Adolescent major depressive disorder (MDD) is associated with altered restingstate connectivity between the default mode network (DMN) and the salience network (SN), which are involved in self-referential processing and detecting and filtering salient stimuli, respectively. Using spectral dynamical causal modelling, we investigated the effective connectivity and input sensitivity between key nodes of these networks in 30 adolescents with MDD and 32 healthy controls while undergoing resting-state fMRI. We found that the DMN received weaker inhibition from the SN and that the medial prefrontal cortex and the anterior cingulate cortex showed reduced self-inhibition in MDD, making them more prone to external influences. Moreover, we found that selective serotonin reuptake inhibitor (SSRI) intake was associated with decreased and increased self-inhibition of the SN and DMN, respectively, in patients. Our findings suggest that adolescent MDD is characterized by a hierarchical imbalance between the DMN and the SN, which could affect the integration of emotional and self-related information. We propose that SSRIs may help restore network function by modulating excitatory/inhibitory balance in the DMN and the SN. Our study highlights the potential of prefrontal-amygdala interactions as a biomarker and a therapeutic target for adolescent depression. [ABSTRACT FROM AUTHOR]

The default mode network (DMN) is a large-scale brain network known to be suppressed during a wide range of cognitive tasks. However, our comprehension of its role in naturalistic and unconstrained behaviors has remained elusive because most research on the DMN has been conducted within the restrictive confines of MRI scanners. Here, we use multisite GCaMP (a genetically encoded calcium indicator) fiber photometry with simultaneous videography to probe DMN function in awake, freely exploring rats. We examined neural dynamics in three core DMN nodes--the retrosplenial cortex, cingulate cortex, and prelimbic cortex--as well as the anterior insula node of the salience network, and their association with the rats' spatial exploration behaviors. We found that DMN nodes displayed a hierarchical functional organization during spatial exploration, characterized by stronger coupling with each other than with the anterior insula. Crucially, these DMN nodes encoded the kinematics of spatial exploration, including linear and angular velocity. Additionally, we identified latent brain states that encoded distinct patterns of time-varying exploration behaviors and found that higher linear velocity was associated with enhanced DMN activity, heightened synchronization among DMN nodes, and increased anticorrelation between the DMN and anterior insula. Our findings highlight the involvement of the DMN in collectively and dynamically encoding spatial exploration in a real-world setting. Our findings challenge the notion that the DMN is primarily a "task-negative" network disengaged from the external world. By illuminating the DMN's role in naturalistic behaviors, our study underscores the importance of investigating brain network function in ecologically valid contexts. [ABSTRACT FROM AUTHOR]

A triple network model consisting of a default network, a salience network, and a central executive network has recently been used to understand connectivity patterns in cognitively normal versus dysfunctional brains. This study aimed to explore changes in the dynamic connectivity of triplet network in mild traumatic brain injury (mTBI) and its relationship to cognitive performance. In this work, we acquired resting-state functional magnetic resonance imaging (fMRI) data from 30 mTBI patients and 30 healthy controls (HCs). Independent component analysis, sliding time window correlation, and k-means clustering were applied to resting-state fMRI data. Further, we analyzed the relationship between changes in dynamic functional connectivity (FC) parameters and clinical variables in mTBI patients. The results showed that the dynamic functional connectivity of the brain triple network was clustered into five states. Compared with HC, mTBI patients spent longer in state 1, which is characterized by weakened dorsal default mode network (DMN) and anterior salience network (SN) connectivity, and state 3, which is characterized by a positive correlation between DMN and SN internal connectivity. Mild TBI patients had fewer metastases in different states than HC patients. In addition, the mean residence time in state 1 correlated with Montreal Cognitive Assessment scores in mTBI patients; the number of transitions between states correlated with Glasgow Coma Score in mTBI patients. Taken together, our findings suggest that the dynamic properties of FC in the triple network of mTBI patients are abnormal, and provide a new perspective on the pathophysiological mechanism of cognitive impairment from the perspective of dynamic FC. [ABSTRACT FROM AUTHOR]

Idiopathic generalized epilepsy (IGE) is characterized by cryptogenic etiology and the striatum and cerebellum are recognized as modulators of epileptic network. We collected simultaneous electroencephalogram and functional magnetic resonance imaging data from 145 patients with IGE, 34 of whom recorded interictal epileptic discharges (IEDs) during scanning. In states without IEDs, hierarchical connectivity was performed to search core cortical regions which might be potentially modulated by striatum and cerebellum. Node–node and edge–edge moderation models were constructed to depict direct and indirect moderation effects in states with and without IEDs. Patients showed increased hierarchical connectivity with sensorimotor cortices (SMC) and decreased connectivity with regions in the default mode network (DMN). In the state without IEDs, striatum, cerebellum, and thalamus were linked to weaken the interactions of regions in the salience network (SN) with DMN and SMC. In periods with IEDs, overall increased moderation effects on the interaction between regions in SN and DMN, and between regions in DMN and SMC were observed. The thalamus and striatum were implicated in weakening interactions between regions in SN and SMC. The striatum and cerebellum moderated the cortical interaction among DMN, SN, and SMC in alliance with the thalamus, contributing to the dysfunction in states with and without IEDs in IGE. The current work revealed state-specific modulation effects of striatum and cerebellum on thalamocortical circuits and uncovered the potential core cortical targets which might contribute to develop new clinical neuromodulation techniques. [ABSTRACT FROM AUTHOR]

Previous studies have shown an association between cigarette use and altered resting-state functional connectivity (rsFC) in many large-scale networks, sometimes complemented by measures of cortical atrophy. In this study, we aimed to further explore the neural differences between smokers and healthy non-smokers through the integration of functional and structural analyses. Imaging data of fifty-two smokers and forty-five non-smokers were analyzed through an independent component analysis for group differences in rsFC. Smokers showed lower rsFC within the dorsal attention network (DAN) in the left superior and middle frontal gyrus and left superior division of the lateral occipital cortex compared to non-smokers; moreover, cigarette use was found to be associated with reduced grey matter volume in the left superior and middle frontal gyrus and right orbitofrontal cortex, partly overlapping with functional findings. Within smokers, daily cigarette consumption was positively associated with increased rsFC within the cerebellar network and the default mode network and decreased rsFC within the visual network and the salience network, while carbon monoxide level showed a positive association with increased rsFC within the sensorimotor network. Our results suggest that smoking negatively impacts rsFC within the DAN and that changes within this network might serve as a circuit-based biomarker for structural deficits. [ABSTRACT FROM AUTHOR]

Highlights: What are the main findings? SN dysfunction is the common denominator of insomnia, schizophrenia (SCZ), and frontotemporal dementia behavioral variant (bvFTD). What is the implication of the main findings? The diagnosis of bvFTD is often missed or misdiagnosed in forensic institutions. To ensure adequate placement and treatment planning, courts and clinicians require education to differentiate bvFTD from SCZ. Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. Since the brain salience network is likely the common denominator for insomnia, neuropsychiatric and neurodegenerative disorders, here, we focus on the pathology of this neuronal assembly and its likely driver, the dysfunctional neuronal and mitochondrial membrane. We also discuss potential treatment strategies ranging from membrane lipid replacement to mitochondrial transplantation. The aims of this review are threefold: 1. Examining the causes of insomnia in forensic detainees with severe mental illness, as well as its role in predisposing them to neurodegenerative disorders. 2. Educating State hospital and prison clinicians on frontotemporal dementia behavioral variant, a condition increasingly diagnosed in older first offenders which is often missed due to the absence of memory impairment. 3. Introducing clinicians to natural compounds that are potentially beneficial for insomnia and severe mental illness. [ABSTRACT FROM AUTHOR]

Chronic pain is a source of substantial physical and psychological suffering, yet a clear understanding of the pathogenesis of chronic pain is lacking. Repeated studies have reported an altered behaviour of the salience network (SN) and default mode network (DMN) in people with chronic pain, and a majority of these studies report an altered behaviour of the dorsal ventromedial prefrontal cortex (vmPFC) within the anterior DMN. In this topical review, we therefore focus specifically on the role of the dorsal vmPFC in chronic pain to provide an updated perspective on the cortical mechanisms of chronic pain. We suggest that increased activity in the dorsal vmPFC may reflect maladaptive overthinking about the meaning of pain for oneself and one's actions. We also suggest that such overthinking, if negative, may increase the personal "threat" of a given context, as possibly reflected by increased activity in, and functional connectivity to, the anterior insular cortex within the SN. [ABSTRACT FROM AUTHOR]

Background: An imbalance between model-based and model-free decision-making systems is a common feature in addictive disorders. However, little is known about whether similar decision-making deficits appear in internet gaming disorder (IGD). This study compared neurocognitive features associated with model-based and model-free systems in IGD and alcohol use disorder (AUD). Method: Participants diagnosed with IGD (n 5 22) and AUD (n 5 22), and healthy controls (n 5 30) performed the two-stage task inside the functional magnetic resonance imaging (fMRI) scanner. We used computational modeling and hierarchical Bayesian analysis to provide a mechanistic account of their choice behavior. Then, we performed a model-based fMRI analysis and functional connectivity analysis to identify neural correlates of the decision-making processes in each group. Results: The computational modeling results showed similar levels of model-based behavior in the IGD and AUD groups. However, we observed distinct neural correlates of the model-based reward prediction error (RPE) between the two groups. The IGD group exhibited insula-specific activation associated with model-based RPE, while the AUD group showed prefrontal activation, particularly in the orbitofrontal cortex and superior frontal gyrus. Furthermore, individuals with IGD demonstrated hyper-connectivity between the insula and brain regions in the salience network in the context of model-based RPE. Discussion and Conclusions: The findings suggest potential differences in the neurobiological mechanisms underlying model-based behavior in IGD and AUD, albeit shared cognitive features observed in computational modeling analysis. As the first neuroimaging study to compare IGD and AUD in terms of the model-based system, this study provides novel insights into distinct decision-making processes in IGD. [ABSTRACT FROM AUTHOR]

Aesthetic experiences have the potential to promote learning and creativity by enhancing the ability to understand complexity and to integrate novel or disparate information. Offering a theoretical framework for understanding the cognitive benefits of aesthetic experiences, this paper argues they are the necessary outcome of human learning, in which natural objects or artworks are evaluated in a multi-dimensional preference space shaped by Bayesian prediction. In addition, it contends that the brain-states underlying aesthetic experiences harness configurations of the apex three transmodal neural systems--the default mode network, the central executive network, and the salience network--that may offer information-processing advantages by recruiting the brain's high-power communication hubs, thus enhancing potential for learning gain. [ABSTRACT FROM AUTHOR]

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic condition with core symptoms of fatigue and cognitive dysfunction, suggesting a key role for the central nervous system in the pathophysiology of this disease. Several studies have reported altered functional connectivity (FC) related to motor and cognitive deficits in ME/CFS patients. In this study, we compared functional connectivity differences between 31 ME/CFS and 15 healthy controls (HCs) using 7 Tesla MRI. Functional scans were acquired during a cognitive Stroop color-word task, and blood oxygen level-dependent (BOLD) time series were computed for 27 regions of interest (ROIs) in the cerebellum, brainstem, and salience and default mode networks. A region-based comparison detected reduced FC between the pontine nucleus and cerebellum vermis IX (p = 0.027) for ME/CFS patients compared to HCs. Our ROI-to-voxel analysis found significant impairment of FC within the ponto-cerebellar regions in ME/CFS. Correlation analyses of connectivity with clinical scores in ME/CFS patients detected associations between FC and 'duration of illness' and 'memory scores' in salience network hubs and cerebellum vermis and between FC and 'respiratory rate' within the medulla and the default mode network FC. This novel investigation is the first to report the extensive involvement of aberrant ponto-cerebellar connections consistent with ME/CFS symptomatology. This highlights the involvement of the brainstem and the cerebellum in the pathomechanism of ME/CFS. [ABSTRACT FROM AUTHOR]

Background: Transcranial pulse stimulation (TPS) is a novel noninvasive ultrasonic brain stimulation that can increase cortical and corticospinal excitability, induce neuroplasticity, and increase functional connectivity within the brain. Several trials have confirmed its potential in treating Alzheimer's disease (AD). Objective: To investigate the effect and safety of TPS on AD. Design: A systematic review. Methods: PubMed, Embase via Ovid, Web of Science, Cochrane Library, CNKI (China National Knowledge Infrastructure), VIP (China Science and Technology Journal Database), and WanFang were searched from inception to April 1, 2023. Study selection, data extraction, and quality evaluation of the studies were conducted by two reviewers independently, with any controversy resolved by consensus. The Methodological Index for Nonrandomized Studies was used to assess the risk of bias. Results: Five studies were included in this review, with a total of 99 patients with AD. For cognitive performance, TPS significantly improved the scores of the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) test battery, Alzheimer's Disease Assessment Scale (cognitive), Montreal Cognitive Assessment, and Mini‐Mental Status Examination. For depressive symptoms, TPS significantly reduced the scores of the Alzheimer's Disease Assessment Scale (affective), Geriatric Depression Score, and Beck Depression Inventory. By functional magnetic resonance imaging, studies have shown that TPS improved cognitive performance in AD patients by increasing functional connectivity in the hippocampus, parahippocampal cortex, precuneus, and parietal cortex, and activating cortical activity in the bilateral hippocampus. TPS alleviated depressive symptoms in AD patients by decreasing functional connectivity between the ventromedial network (left frontal orbital cortex) and the salience network (right anterior insula). Adverse events in this review, including headache, worsening mood, jaw pain, nausea, and drowsiness, were reversible and lasted no longer than 1 day. No serious adverse events or complications were observed. Conclusions: TPS is promising in improving cognitive performance and reducing depressive symptoms in patients with AD. TPS may be a safe adjunct therapy in the treatment of AD. However, these findings lacked a sham control and were limited by the small sample size of the included studies. Further research may be needed to better explore the potential of TPS. Patient and Public Involvement: Patients and the public were not involved in this study. [ABSTRACT FROM AUTHOR]

The effects of age and gender on large-scale resting-state networks (RSNs) reflecting within- and between-network connectivity in the healthy brain remain unclear. This study investigated how age and gender influence the brain network roles and topological properties underlying the ageing process. Ten RSNs were constructed based on 998 participants from the REST-meta-MDD cohort. Multivariate linear regression analysis was used to examine the independent and interactive influences of age and gender on large-scale RSNs and their topological properties. A support vector regression model integrating whole-brain network features was used to predict brain age across the lifespan and cognitive decline in an Alzheimer's disease spectrum (ADS) sample. Differential effects of age and gender on brain network roles were demonstrated across the lifespan. Specifically, cingulo-opercular, auditory, and visual (VIS) networks showed more incohesive features reflected by decreased intra-network connectivity with ageing. Further, females displayed distinctive brain network trajectory patterns in middle-early age, showing enhanced network connectivity within the fronto-parietal network (FPN) and salience network (SAN) and weakened network connectivity between the FPN-somatomotor, FPN-VIS, and SAN-VIS networks. Age — but not gender — induced widespread decrease in topological properties of brain networks. Importantly, these differential network features predicted brain age and cognitive impairment in the ADS sample. By showing that age and gender exert specific dispersion of dynamic network roles and trajectories across the lifespan, this study has expanded our understanding of age- and gender-related brain changes with ageing. Moreover, the findings may be useful for detecting early-stage dementia. [ABSTRACT FROM AUTHOR]

Successful recovery from stress is integral for adaptive responding to the environment. At a cellular level, this involves (slow genomic) actions of cortisol, which alter or reverse rapid effects of noradrenaline and cortisol associated with acute stress. At the network scale, stress recovery is less well understood but assumed to involve changes within salience-, executive control-, and default mode networks. To date, few studies have investigated this phase and directly tested these assumptions. Here, we present results from a double-blind, placebo-controlled, between-group paradigm (N  = 165 healthy males) administering 10 mg oral yohimbine and/or 10 mg oral hydrocortisone two hours prior to resting state scanning. We found no changes in within-network connectivity of the three networks, both after single and combined drug administration. We further report the results of Bayesian parameter inference to provide evidence for the null hypothesis. Our results contrast with previous findings, which may be attributable to systematic differences between paradigms, highlighting the need to isolate paradigm-specific effects from those related to stress. [ABSTRACT FROM AUTHOR]

Background: Alterations in resting state functional connectivity (rs-FC) in Crohn's Disease (CD) have been documented in default mode network (DMN) and frontal parietal network (FPN) areas, visual, cerebellar, salience and attention restingstate-networks (RSNs), constituting a CD specific neural phenotype. To date, most studies are in patients in remission, with limited studies in active disease. Methods: Twenty five active CD cases and 25 age-, BMI- and gender-matched healthy controls (HC) were recruited to a resting-state-functional Magnetic Resonance Imaging (rs-fMRI) study. Active disease was defined as C-reactive protein>5 mg/dL, faecal calprotectin>250 µg/g, or through ileocolonoscopy or MRE. rs-fMRI data were analysed using independent component analysis (ICA) and dual regression. Differences in RSNs between HCs and active CD were assessed, and rs-FC was associated with disease duration and abdominal pain. Results: Increased connectivity in the FPN (fusiform gyrus, thalamus, caudate, posterior cingulate cortex, postcentral gyrus) and visual RSN (orbital frontal cortex) were observed in CD versus HC. Decreased activity was observed in the salience network (cerebellum, postcentral gyrus), DMN (parahippocampal gyrus, cerebellum), and cerebellar network (occipital fusiform gyrus, cerebellum) in CD versus HCs. Greater abdominal pain scores were associated with lower connectivity in the precuneus (visual network) and parietal operculum (salience network), and higher connectivity in the cerebellum (frontal network). Greater disease duration was associated with greater connectivity in the middle temporal gyrus and planum temporale (visual network). Conclusion: Alterations in rs-FC in active CD in RSNs implicated in cognition, attention, emotion, and pain may represent neural correlates of chronic systemic inflammation, abdominal pain, disease duration, and severity. [ABSTRACT FROM AUTHOR]

Focused attention meditation (FAM) training has been shown to improve attention, but the neural basis of FAM on attention has not been thoroughly understood. Here, we aim to investigate the neural effect of a 2-month FAM training on novice meditators in a visual oddball task (a frequently adopted task to evaluate attention), evaluated with both ASL and BOLD fMRI. Using ASL, activation was increased in the middle cingulate (part of the salience network, SN) and temporoparietal (part of the frontoparietal network, FPN) regions; the FAM practice time was negatively associated with the longitudinal changes in activation in the medial prefrontal (part of the default mode network, DMN) and middle frontal (part of the FPN) regions. Using BOLD, the FAM practice time was positively associated with the longitudinal changes of activation in the inferior parietal (part of the dorsal attention network, DAN), dorsolateral prefrontal (part of the FPN), and precentral (part of the DAN) regions. The effect sizes for the activation changes and their association with practice time using ASL are significantly larger than those using BOLD. Our study suggests that FAM training may improve attention via modulation of the DMN, DAN, SN, and FPN, and ASL may be a sensitive tool to study the FAM effect on attention. [ABSTRACT FROM AUTHOR]