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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.

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]

Thalamic abnormalities in schizophrenia are recognized, alongside cognitive deficits. However, the current findings about these abnormalities during the prodromal period remain relatively few and inconsistent. This study applied multimodal methods to explore the alterations in thalamic function and structure and their relationship with cognitive function in first-episode schizophrenia (FES) patients and ultra-high-risk (UHR) individuals, aiming to affirm the thalamus's role in schizophrenia development and cognitive deficits. 75 FES patients, 60 UHR individuals, and 60 healthy controls (HC) were recruited. Among the three groups, gray matter volume (GMV) and functional connectivity (FC) were evaluated to reflect the structural and functional abnormalities in the thalamus. Pearson correlation was used to calculate the association between these abnormalities and cognitive impairments. No significant difference in GMV of the thalamus was found among the abovementioned three groups. Compared with HC individuals, FES patients had decreased thalamocortical FC mostly in the thalamocortical triple network, including the default mode network (DMN), salience network (SN), and executive control network (ECN). UHR individuals had similar but milder dysconnectivity as the FES group. Furthermore, FC between the left thalamus and right putamen was significantly correlated with execution speed and attention in the FES group. Our findings revealed decreased thalamocortical FC associated with cognitive deficits in FES and UHR subjects. This improves our understanding of the functional alterations in thalamus in prodromal stage of schizophrenia and the related factors of the cognitive impairment of the disease. ClinicalTrials.gov NCT03965598 ; https://clinicaltrials.gov/ct2/show/NCT03965598. [ABSTRACT FROM AUTHOR]

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

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]

Autonomous sensory meridian response (ASMR) is characterized by a tingling sensation with a feeling of relaxation and a state of flow. We explore the neural underpinnings and comorbidities of ASMR and related phenomena with altered sensory processing. These phenomena include sensory processing sensitivity (SPS), synaesthesia, Alice in Wonderland syndrome and misophonia. The objective of this article is to uncover the shared neural substrates and distinctive features of ASMR and its counterparts. ASMR, SPS and misophonia exhibit common activations in the brain regions associated with social cognition, emotion regulation and empathy. Nevertheless, ASMR responders display reduced connectivity in the salience network (SN), while individuals with SPS exhibit increased connectivity in the SN. Furthermore, ASMR induces relaxation and temporarily reduces symptoms of depression, in contrast to SPS and misophonia, which are linked to depression. These observations lead us to propose that ASMR is a distinct phenomenon owing to its attention dispatch mechanism and its connection with emotion regulation. We suggest that increased activations in the insula, along with reduction in connectivity within the salience and default mode networks in ASMR responders, may account for their experiences of relaxation and flow states. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'. [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: Recently, subjective cognitive decline (SCD) was proposed as an early risk factor for future Alzheimer's disease (AD). Objective: In this study, we investigated whether accelerated long-term forgetting (ALF), assessed with extended testing intervals than those adopted in clinical practice, might be a cognitive feature of SCD. Using an explorative MRI analysis of the SCD sample, we attempted to investigate the areas most likely involved in the ALF pattern. Methods: We recruited 31 individuals with SCD from our memory clinic and subdivided them based on their rate of memory complaints into mild SCDs (n = 18) and severe SCDs (n = 13). A long-term forgetting procedure, involving the recall of verbal and visuo-spatial material at four testing delays (i.e., immediate, 30 min, 24 h, and 7 days post-encoding) was used to compare the two sub-groups of SCDs with a healthy control group (HC; n = 16). Results: No significant between-group difference was found on the standard neuropsychological tests, nor in the immediate and 30 min recall of the experimental procedure. By contrast, on the verbal test severe SCDs forgot significantly more than HCs in the prolonged intervals (i.e., 24 h and 7 days), with the greatest decline between 30 min and 24 h. Finally, in the whole SCD sample, we found significant associations between functional connectivity values within some cortical networks involved in memory (default mode network, salience network, and fronto-parietal network) and verbal long-term measures. Conclusions: Our preliminary findings suggest that long-term forgetting procedures could be a sensitive neuropsychological tool for detecting memory concerns in SCDs, contributing to early AD detection. [ABSTRACT FROM AUTHOR]

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

Both ruminative thought processes and adverse childhood experiences (ACEs) are well-established risk factors for the emergence and maintenance of depression. However, the neurobiological mechanisms underlying these associations remain poorly understood. We examined resting-state functional magnetic resonance imaging data (3 T Tim Trio MR scanner; Siemens, Erlangen) of 44 individuals diagnosed with an acute depressive episode. Specifically, we focused on investigating functional brain activity and connectivity within and between three large-scale neural networks associated with processes affected in depression: the default mode network (DMN), the salience network (SN), and the central executive network (CEN). Correlational and regression-based analyses were performed. Our regions of interest analyses revealed that region-specific spontaneous neural activity in the anterior DMN was associated with self-reported trait rumination, specifically, the pregenual anterior cingulate cortex (pgACC). Furthermore, using a liberal statistical threshold, we found that spontaneous neural activity of the ventromedial prefrontal cortex and the pgACC were associated with depression symptom severity. Neither spontaneous neural activity in the SN and CEN nor functional connectivity within and across the investigated networks was associated with depression severity or rumination. Furthermore, there was no association between ACEs and brain activity and connectivity. Lack of a formal control group or low-risk group for comparison. Overall, our results indicate network-specific changes in spontaneous brain activity, that are linked to both depression severity and rumination. Findings underscore the crucial role of the pgACC in depression and contribute to a dimensional and symptom-based understanding of depression-related network imbalances. • Rumination and adverse childhood experiences are risk factors for depression. • Spontaneous neural activity in the pgACC at rest was associated with trait rumination. • Spontaneous neural activity in the pgACC and vmPFC at rest was associated with depression severity. • We found no associations between self-report measures and FC across regions of interest. • We found no associations between adverse childhood experiences and brain activity/connectivity. [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]

Serotonergic psychedelics, such as psilocybin, alter perceptual and cognitive systems that are functionally integrated with the amygdala. These changes can alter cognition and emotions that are hypothesized to contribute to their therapeutic utility. However, the neural mechanisms of cognitive and subcortical systems altered by psychedelics are not well understood. We used resting-state functional magnetic resonance images collected during a randomized, double-blind, placebo-controlled clinical trial of 24 healthy adults under 0.2 mg/kg psilocybin to estimate the directed (i.e., effective) changes between the amygdala and 3 large-scale resting-state networks involved in cognition. These networks are the default mode network, the salience network, and the central executive network. We found a pattern of decreased top-down effective connectivity from these resting-state networks to the amygdala. Effective connectivity decreased within the default mode network and salience network but increased within the central executive network. These changes in effective connectivity were statistically associated with behavioral measures of altered cognition and emotion under the influence of psilocybin. Our findings suggest that temporary amygdala signal attenuation is associated with mechanistic changes to resting-state network connectivity. These changes are significant for altered cognition and perception and suggest targets for research investigating the efficacy of psychedelic therapy for internalizing psychiatric disorders. More broadly, our study suggests the value of quantifying the brain's hierarchical organization using effective connectivity to identify important mechanisms for basic cognitive function and how they are integrated to give rise to subjective experiences. [ABSTRACT FROM AUTHOR]

Emotion and executive control are often conceptualized as two distinct modes of human brain functioning. Little, however, is known about how the dynamic organization of large-scale functional brain networks that support flexible emotion processing and executive control, especially their interactions. The amygdala and prefrontal systems have long been thought to play crucial roles in these processes. Recent advances in human neuroimaging studies have begun to delineate functional organization principles among the large-scale brain networks underlying emotion, executive control, and their interactions. Here, we propose a dynamic brain network model to account for interactive competition between emotion and executive control by reviewing recent resting-state and task-related neuroimaging studies using network-based approaches. In this model, dynamic interactions among the executive control network, the salience network, the default mode network, and sensorimotor networks enable dynamic processes of emotion and support flexible executive control of multiple processes; neural oscillations across multiple frequency bands and the locus coeruleus−norepinephrine pathway serve as communicational mechanisms underlying dynamic synergy among large-scale functional brain networks. This model has important implications for understanding how the dynamic organization of complex brain systems and networks empowers flexible cognitive and affective functions. [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]

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.

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

Chronic insomnia disorder (CID) is commonly associated with mood disorders. The cingulate gyrus (CG) plays a critical role in the pathophysiology of CID and anxiety. However, the specific characteristics of altered brain networks in the CG in CID with anxiety remain unclear. This study aimed to investigate the characteristics of CG functional connectivity (FC) in CID with and without anxiety. Methods: Resting-state functional magnetic resonance imaging was conducted on 92 CID and 36 healthy controls (HC). CID was divided into CID with anxiety (CID-A, N = 37) and CID without anxiety (CID-NA, N = 55) groups based on anxiety scores. Using the Human Brainnetome Atlas, the subregion CG FC network was constructed. Compared with HC, CID showed significantly decreased CG FC with the precuneus, middle frontal gyrus (MFG), and hippocampus, while showing significantly increased CG FC with the middle temporal gyrus (MTG)/superior temporal gyrus (STG). In contrast, CID-A showed significantly decreased CG FC with the salience network (insular, putamen) and default mode network (MTG/STG and inferior parietal lobule), while showing significantly increased CG FC with the thalamus and MFG compared to CID-NA. Further, CID-A and CID-NA could be classified with 84.21 % accuracy by using the CG FCs as features. Among these features, the CG FC with MFG, thalamus, and putamen had the highest contribution weights. This study revealed specific changes in the brain network of the CG subregion in CID-A. Understanding these CG FC alterations can help identify potential biomarkers specific to CID-A, which may be valuable for early detection and differentiation from other CID subtypes. • To explore the cingulate gyrus (CG) subregions FC alteration in CID with anxiety (CID-A). • CID-A shown specific CG FC with default mode network and salience network. • Machine learning with CG FC features classifies CID-A accurately at 84.21 %. • The CG subregional FC alterations may contribute to potential biomarkers for CID-A. [ABSTRACT FROM AUTHOR]

The purpose of this study was to clarify the relationships between glycemia and function of the autonomic nervous system (ANS), assessed via resting-state functional connectivity (FC) and heart-rate variability (HRV). Data for this study were extracted from the Leipzig Study for Mind-Body-Emotion Interactions, including 146 healthy adults (114 young, 32 older). Variables of interest were glycated hemoglobin (HbA1c), resting-state FC in the salience aspect of the central-autonomic (S-CAN) and salience network (SN) and HRV (RMSSD and high-frequency HRV (HF-HRV)). HbA1c was inversely correlated with FC in the S-CAN but not SN. HbA1c was inversely correlated with HRV. Both RMSSD and log(HF-HRV) were correlated with FC in the S-CAN and SN. Age- (not sex-related) differences were observed in the Hb1Ac-FC associations (stronger in older adults) while sex- (not age-related) differences were observed in the HRV-FC (stronger in females). These findings extend the diabetes literature to healthy adults in relating glycemia and brain function. The age- and sex-related differences in these relationships highlight the need to account for the potential effects of age and sex in future investigations. • Glycated hemoglobin inversely related with functional connectivity (FC) in controls. • High heart rate variability (RMSSD) was associated with high FC. • Age- but not sex-related differences found in the association between Hb1Ac and FC. • Sex- but not age-related differences found in the association between HRV and FC. [ABSTRACT FROM AUTHOR]

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

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]

How do people identify new and better lifegoals for themselves? The goal breakthrough model (GBM) purports to answer this question. The GBM draws from creative process theories of preparation, incubation, illumination, and elaboration to explain how people "cross the Rubicon" to new purposes, in response to felt dissatisfaction. Neuroscience research supporting the GBM is reviewed, highlighting brain‐sequences linking Default Mode Network activity, Cognitive Control Network activity, and Salience Network activity. This understanding of the neural basis of creative goal‐functioning informs an elaborated version of the GBM, one that is less linear and more dynamic than its predecessor model. Overall, the GBM proposes a novel explanation for how people can actively prompt their nonconscious minds to provide new and better behavioral alternatives to consider. [ABSTRACT FROM AUTHOR]

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

For at least 150,000 years, the human body has been culturally modified by the wearing of personal ornaments and probably by painting with red pigment. The present study used functional magnetic resonance imaging to explore the brain networks involved in attributing social status from face decorations. Results showed the fusiform gyrus, orbitofrontal cortex, and salience network were involved in social encoding, categorization, and evaluation. The hippocampus and parahippocampus were activated due to the memory and associative skills required for the task, while the inferior frontal gyrus likely interpreted face ornaments as symbols. Resting-state functional connectivity analysis clarified the interaction between these regions. The study highlights the importance of these neural interactions in the symbolic interpretation of social markers on the human face, which were likely active in early Homo species and intensified with Homo sapiens populations as more complex technologies were developed to culturalize the human face. [ABSTRACT FROM AUTHOR]

Background: Insomnia is a common sleep disorder with significant negative impacts on emotional states; however, the underlying mechanism of insomnia with comorbid emotional dysregulation remains largely unknown. The salience network (SN) plays an important role in both sleep and emotional regulation. The study aimed to explore the specific alterations in functional connectivity (FC) within the SN in insomnia patients. Methods: A total of 30 eligible patients with insomnia disorder (ID group) and 30 healthy controls (HC group) underwent resting-state functional magnetic resonance imaging (fMRI) scanning and psychometric assessments. Differences in FC within the SN were examined using seed-based region-to-region connectivity analysis. Results: Compared with healthy controls, patients with insomnia showed increased FC within the SN, mainly between the anterior cingulate cortex (ACC) and right superior frontal gyrus (SFG), the right SFG and right supramarginal gyrus (SMG), and between the right insular (INS) and left SMG (P<0.05). Additionally, significant correlations were observed between increased FC and the Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), and Hamilton Anxiety Rating Scale (HAMA) scores (P<0.05, after Bonferroni correction). Conclusions: These results suggest that increased FC within the SN may be related to poor sleep quality and negative emotions, highlighting the importance of the SN in the pathophysiological mechanisms of insomnia with comorbid emotional dysregulation. [ABSTRACT FROM AUTHOR]

Psilocybin is a serotonergic psychedelic drug under assessment as a potential therapy for treatment-resistant and major depression. Heterogeneous treatment responses raise interest in predicting the outcome from baseline data. A machine learning pipeline was implemented to investigate baseline resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI) as a predictor of symptom severity in psilocybin monotherapy for treatment-resistant depression (16 patients administered two 5 mg capsules followed by 25 mg, separated by one week). Generalizability was tested in a sample of 22 patients who participated in a psilocybin vs. escitalopram trial for moderate-to-severe major depression (two separate doses of 25 mg of psilocybin 3 weeks apart plus 6 weeks of daily placebo vs. two separate doses of 1 mg of psilocybin 3 weeks apart plus 6 weeks of daily oral escitalopram). The analysis was repeated using both samples combined. Functional connectivity of visual, default mode and executive networks predicted early symptom improvement, while the salience network predicted responders up to 24 weeks after treatment (accuracy≈0.9). Generalization performance was borderline significant. Consistent results were obtained from the combined sample analysis. Fronto-occipital and fronto-temporal coupling predicted early and late symptom reduction, respectively. The number of participants and differences between the two datasets limit the generalizability of the findings, while the lack of a placebo arm limits their specificity. Baseline neurophysiological measurements can predict the outcome of psilocybin treatment for depression. Future research based on larger datasets should strive to assess the generalizability of these predictions. • Baseline connectivity predicted responders up to 24 weeks after psilocybin treatment. • Visual, default mode and executive networks predicted early improvement. • Salience network was relevant for the prediction of late responders to treatment. • Fronto-occipital and fronto-temporal coupling predicted early and late improvement. [ABSTRACT FROM AUTHOR]

• Differences in directed functional connectivity (FC) within and between triple networks were confirmed in pMCI and sMCI. • The changes in directional FC are associated with cognitive function. • Integrate pathological indicators, comprehensively analyze MCI changes. Mild cognitive impairment includes two distinct subtypes, namely progressive mild cognitive impairment and stable mild cognitive impairment. While alterations in extensive functional connectivity have been observed in both subtypes, limited attention has been given to directed functional connectivity. A triple network, composed of the central executive network, default mode network, and salience network, is considered to be the core cognitive network. We evaluated the alterations in directed functional connectivity within and between the triple network in progressive and stable mild cognitive impairment groups and investigated its role in predicting disease conversion. Resting-state functional magnetic resonance imaging was used to analyze directed functional connectivity within the triple networks. A correlation analysis was performed to investigate potential associations between altered directed functional connectivity within the triple networks and the neurocognitive performance of the participants. Our study revealed significant differences in directed functional connectivity within and between the triple network in the progressive and stable mild cognitive impairment groups. Altered directed functional connectivity within the triple network was involved in episodic memory and executive function. Thus, the directed functional connectivity of the triple network may be used as an imaging marker of mild cognitive impairment. [ABSTRACT FROM AUTHOR]

We characterized the neurocognitive profile of communed-based individuals and unaffected siblings of patients with psychosis from Brazil reporting psychotic experiences (PEs). We also analyzed associations between PEs and the intra and inter-functional connectivity (FC) in the Default Mode Network (DMN), the Fronto-Parietal Network (FPN) and the Salience Network (SN) measured by functional magnetic resonance imaging. The combined sample of communed-based individuals and unaffected siblings of patients with psychosis comprised 417 (neurocognition) and 85 (FC) volunteers who were divided as having low (<75th percentile) and high (≥75th percentile) PEs (positive, negative, and depressive dimensions) assessed by the Community Assessment of Psychic Experiences. The neurocognitive profile and the estimated current brief intellectual quotient (IQ) were assessed using the digit symbol (processing speed), arithmetic (working memory), block design (visual learning) and information (verbal learning) subtests of Wechsler Adult Intelligence Scale-third edition. Logistic regression models were performed for neurocognitive analysis. For neuroimaging, we used the CONN toolbox to assess FC between the specified regions, and ROI-to-ROI analysis. In the combined sample, high PEs (all dimensions) were related to lower processing speed performance. High negative PEs were related to poor visual learning performance and lower IQ, while high depressive PEs were associated with poor working memory performance. Those with high negative PEs presented FPN hypoconnectivity between the right and left lateral prefrontal cortex. There were no associations between PEs and the DMN and SN FC. Brazilian individuals with high PEs showed neurocognitive impairments like those living in wealthier countries. Hypoconnectivity in the FPN in a community sample with high PEs is coherent with the hypothesis of functional dysconnectivity in schizophrenia. [ABSTRACT FROM AUTHOR]

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]

The basal forebrain cholinergic neurons provide acetylcholine to the cortex via large projections. Recent molecular imaging work in humans indicates that the cortical cholinergic innervation is not uniformly distributed, but rather may disproportionately innervate cortical areas relevant to supervisory attention. In this study, we therefore reexamined the spatial relationship between acetylcholinergic modulation and attention in the human cortex using meta‐analytic strategies targeting both pharmacological and non‐pharmacological neuroimaging studies. We found that pharmaco‐modulation of acetylcholine evoked both increased activity in the anterior cingulate and decreased activity in the opercular and insular cortex. In large independent meta‐analyses of non‐pharmacological neuroimaging research, we demonstrate that during attentional engagement these cortical areas exhibit (1) task‐related co‐activation with the basal forebrain, (2) task‐related co‐activation with one another, and (3) spatial overlap with dense cholinergic innervations originating from the basal forebrain, as estimated by multimodal positron emission tomography and magnetic resonance imaging. Finally, we provide meta‐analytic evidence that pharmaco‐modulation of acetylcholine also induces a speeding of responses to targets with no apparent tradeoff in accuracy. In sum, we demonstrate in humans that acetylcholinergic modulation of midcingulo‐insular hubs of the ventral attention/salience network via basal forebrain afferents may coordinate selection of task relevant information, thereby facilitating cognition and behavior. [ABSTRACT FROM AUTHOR]

Patients with major depressive disorder (MDD) have abnormal functional interaction among large-scale brain networks, indicated by aberrant effective connectivity of the default mode network (DMN), salience network (SN), and dorsal attention network (DAN). However, it remains unclear whether antidepressants can normalize the altered effective connectivity in MDD. In this study, we collected resting-state functional magnetic resonance imaging data from 46 unmedicated patients with MDD at baseline and after 12 weeks of escitalopram treatment. We also collected data from 58 healthy controls (HCs) at the same time point with the same interval. Using spectral dynamic causal modeling and parametric empirical Bayes, we examined group differences, time effect and their interaction on the casual interactions among the regions of interest in the three networks. Compared with HCs, patients with MDD showed increased positive (excitatory) connections within the DMN, decreased positive connections within the SN and DAN, decreased absolute value of negative (inhibitory) connectivity from the SN and DAN to the DMN, and decreased positive connections between the DAN and the SN. Furthermore, we found that six connections related to the DAN showed decreased group differences in effective connectivity between MDD and HCs during follow-up compared to the baseline. Our findings suggest that escitalopram therapy can partly improve the disrupted effective connectivity among high-order brain functional networks in MDD. These findings deepened our understanding of the neural basis of antidepressants' effect on brain function in patients with MDD. • MDD showed abnormal effective connectivity among three key large-scale brain networks (DMN, SN and DAN). • Connections related to the DAN recovered after 12 weeks of escitalopram treatment in MDD patients. • Escitalopram therapy can normalize the disrupted effective connectivity among functional networks in MDD. [ABSTRACT FROM AUTHOR]

Ketamine administration leads to a psychotomimetic state when taken in large bolus doses, making it a valid model of psychosis. Therefore, understanding ketamine's effects on brain functioning is particularly relevant. This meta-analysis focused on neuroimaging studies that examined ketamine-induced brain activation at rest and during a task. Included are 10 resting-state studies and 23 task-based studies, 9 of which were measuring executive functions. Using a stringent statistical threshold (TFCE <0.05), the results showed increased activity at rest in the dorsal anterior cingulate cortex (ACC), and increased activation of the right Heschl's gyrus during executive tasks, following ketamine administration. Uncorrected results showed increased activation at rest in the right (anterior) insula and the right-fusiform gyrus, as well as increased activation during executive tasks in the rostral ACC. Rest-state studies highlighted alterations in core hubs of the salience network, while task-based studies suggested an impact on task-irrelevant brain regions. Increased activation in the rostral ACC may indicate a failure to deactivate the default mode network during executive tasks following ketamine administration. The results are coherent with alterations found in schizophrenia, which confer external validity to the ketamine model of psychosis. Studies investigating the neural mechanisms of ketamine's antidepressant action are warranted. [ABSTRACT FROM AUTHOR]

Conscientiousness is a personality trait that matures from early childhood to late adolescence, yet little is known about its underlying brain mechanisms during this period. To investigate this, our study examined the resting-state functional network connectivity (rsFNC) of 69 school-aged children (mean age = 10.12 years, range = 9–12) using a whole-brain region-of-interest (ROI) based analysis, based on functional magnetic resonance imaging (fMRI). The results indicated a positive association between conscientiousness and the rsFNC between the fronto-parietal network (FPN) and two brain networks: the somatosensory motor-hand network (SMHN) and the auditory network (AN). However, conscientiousness was negatively associated with the rsFNC between FPN and two other networks: the salience network (SN); the default mode network (DMN). Moreover, our results suggest that the FPN may play a hub role in the neural performance of children's conscientiousness. Intrinsic brain networks, particularly those involved in higher-order cognitive functions, impact children's conscientiousness. Therefore, FPN plays an important role in the development of children's personality, providing insight into the neural mechanisms underlying children's personality. [ABSTRACT FROM AUTHOR]

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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.