Salience Network Research Articles

Pilot trial testing the effects of exercise on chemotherapy-induced peripheral neurotoxicity (CIPN) and the interoceptive brain system.

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a prevalent, dose-limiting, tough-to-treat toxicity involving numbness, tingling, and pain in the extremities with enigmatic pathophysiology. This randomized controlled pilot study explored the feasibility and preliminary efficacy of exercise during chemotherapy on CIPN and the role of the interoceptive brain system, which processes bodily sensations. Nineteen patients (65 ± 11 years old, 52% women; cancer type: breast, gastrointestinal, multiple myeloma) starting neurotoxic chemotherapy were randomized to 12 weeks of exercise (home-based, individually tailored, moderate intensity, progressive walking, and resistance training) or active control (nutrition education). At pre-, mid-, and post-intervention, we assessed CIPN symptoms (primary clinical outcome: CIPN-20), CIPN signs (tactile sensitivity using monofilaments), and physical function (leg strength). At pre- and post-intervention, we used task-free ("resting") fMRI to assess functional connectivity in the interoceptive brain system, involving the salience and default mode networks. The study was feasible (74-89% complete data across measures) and acceptable (95% retention). We observed moderate/large beneficial effects of exercise on CIPN symptoms (CIPN-20, 0-100 scale: - 7.9 ± 5.7, effect size [ES] = - 0.9 at mid-intervention; - 4.8 ± 7.3, ES = - 0.5 at post-intervention), CIPN signs (ES = - 1.0 and - 0.1), and physical function (ES = 0.4 and 0.3). Patients with worse CIPN after neurotoxic chemotherapy had lower functional connectivity within the default mode network (R2 = 40-60%) and higher functional connectivity within the salience network (R2 = 20-40%). Exercise tended to increase hypoconnectivity and decrease hyperconnectivity seen in CIPN (R2 = 12%). Exercise during neurotoxic chemotherapy is feasible and may attenuate CIPN symptoms and signs, perhaps via changes in interoceptive brain circuitry. Future work should test for replication with larger samples. Registered Jan 2017 on ClinicalTrials.gov as NCT03021174.

Resting-state alterations in emotion salience and default-mode network connectivity in atypical trajectories of psychotic-like experiences.

Social cognition is commonly altered in people with psychosis. Two main brain networks have been implicated: the default-mode network (DMN), which is associated with socio-cognitive processing, and the salience network (SN) associated with socio-affective processing. Disturbances to the resting-state functional connectivity of these networks have been identified in schizophrenia and high-risk individuals, but there have been no studies in adolescents displaying distinct trajectories of subclinical psychotic-like experiences (PLEs). To address this, the present study measured SN and DMN resting-state connectivity in a unique longitudinally followed sample of youth (n = 92) presenting with typical and atypical 4-year PLE trajectories. Compared to the typically developing low PLE control group, the atypical increasing PLE trajectory displayed reduced connectivity between the SN and DMN, increased connectivity between left and right insula, and widespread dysconnectivity from the insula and amygdala. These alterations are similar to those reported in schizophrenia and clinical high-risk samples, suggesting that early detection may be useful for mapping the developmental trajectories of psychotic disorders.

Unearthing the hidden links: Investigating the functional connectivity between amygdala subregions and brain networks in bipolar disorder through resting-state fMRI

IntroductionBipolar disorder is a multifaceted psychiatric condition characterized by fluctuating activity levels and dysfunctional mood states, oscillating between manic and depressive episodes. These mood disturbances are accompanied by persistent functional and cognitive impairments, even during periods of euthymia. Prior studies have underscored the critical role of amygdala activity in the pathophysiology of bipolar disorder. This research aims to utilize resting-state functional Magnetic Resonance Imaging (rs-fMRI) to explore the functional modifications in the six sub-regions that compose the amygdala of individuals diagnosed with bipolar disorder. MethodThe study encompassed 80 participants, bifurcated into two groups: 40 individuals with bipolar disorder and 40 healthy controls. Each group comprised an equal gender distribution of 20 females and 20 males, ranging in age from 21 to 50 years. Using rs-fMRI, we examined the functional connectivity within six amygdala sub-regions across eight regional functional networks. ResultsComparative analysis between the control group and the bipolar patients revealed that all six amygdala sub-regions demonstrated connectivity with the eight functional brain networks. Notable similarities and disparities were observed in the connectivity patterns between the bipolar group and controls, particularly within the amygdala's sub-regions and other brain networks. The most significant functional connectivity alterations were found with the salience network and the default mode network. Additionally, alterations in the functional connectivity between the amygdala, sensory-motor, and visual networks were noted in bipolar patients. ConclusionThe study's findings highlight the distinct patterns of resting-state functional connectivity of the amygdala and various brain networks in differentiating bipolar patients from healthy controls. These variations suggest the existence of multiple pathophysiological mechanisms contributing to emotional dysregulation in bipolar disorder.

From gut to brain: unveiling probiotic effects through a neuroimaging perspective-A systematic review of randomized controlled trials.

The gut-brain axis, a bidirectional communication network between the gastrointestinal system and the brain, significantly influences mental health and behavior. Probiotics, live microorganisms conferring health benefits, have garnered attention for their potential to modulate this axis. However, their effects on brain function through gut microbiota modulation remain controversial. This systematic review examines the effects of probiotics on brain activity and functioning, focusing on randomized controlled trials using both resting-state and task-based functional magnetic resonance imaging (fMRI) methodologies. Studies investigating probiotic effects on brain activity in healthy individuals and clinical populations (i.e., major depressive disorder and irritable bowel syndrome) were identified. In healthy individuals, task-based fMRI studies indicated that probiotics modulate brain activity related to emotional regulation and cognitive processing, particularly in high-order areas such as the amygdala, precuneus, and orbitofrontal cortex. Resting-state fMRI studies revealed changes in connectivity patterns, such as increased activation in the Salience Network and reduced activity in the Default Mode Network. In clinical populations, task-based fMRI studies showed that probiotics could normalize brain function in patients with major depressive disorder and irritable bowel syndrome. Resting-state fMRI studies further suggested improved connectivity in mood-regulating networks, specifically in the subcallosal cortex, amygdala and hippocampus. Despite promising findings, methodological variability and limited sample sizes emphasize the need for rigorous, longitudinal research to clarify the beneficial effects of probiotics on the gut-brain axis and mental health.

Biological markers of brain network connectivity and pain sensitivity distinguish low coping from high coping Veterans with persistent post-traumatic headache.

Headache is the most common type of pain following mild traumatic brain injury. Roughly half of those with persistent post-traumatic headache (PPTH) also report neck pain which is associated with greater severity and functional impact of headache. This observational cohort study aimed to identify biological phenotypes to help inform mechanism-based approaches in the management of PPTH with and without concomitant neck pain. Thirty-three military Veterans (mean (SD) = 37±16 years, 29 males) with PPTH completed a clinical assessment, quantitative sensory testing, and magnetic resonance imaging of the brain and cervical spine. Multidimensional phenotyping was performed using a Random Forest analysis and Partitioning Around Medoids (PAM) clustering of input features from three biologic domains: 1) resting state functional connectivity (rsFC) of the periaqueductal gray (PAG), 2) quality and size of cervical muscles, and 3) mechanical pain sensitivity and central modulation of pain. Two subgroups were distinguished by biological features that included forehead pressure pain threshold and rsFC between the PAG and selected nodes within the default mode, salience, and sensorimotor networks. Compared to the High Pain Coping group, the Low Pain Coping group exhibited higher pain-related anxiety (p=0.009), higher pain catastrophizing (p=0.004), lower pain self-efficacy (p=0.010), and greater headache-related disability (p=0.012). Findings suggest that greater functional connectivity of pain modulation networks involving the PAG combined with impairments in craniofacial pain sensitivity, but not cervical muscle health, distinguish a clinically important subgroup of individuals with PPTH who are less able to cope with pain and more severely impacted by headache.

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

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

Delay discounting and nucleus accumbens functional connectivity are related to weight status in adolescents from the ABCD study.

Despite the growing epidemic of paediatric obesity, questions remain regarding potential neural mechanisms for individual risk. Delay discounting is a cognitive process of comparison of valuation between immediate and delayed reward, which has been inconsistently linked to weight status. Moreover, central to the brain's reward system is the nucleus accumbens, a region structurally and functionally altered in obesity. This study aimed to examine the relationships between two continuous metrics of weight status, performance on a monetary delay-discounting task and nucleus accumbens functional connectivity in 10-12-year-olds from the Adolescent Brain and Cognitive Development (ABCD) Study. Using multilevel longitudinal linear modelling, we found greater discounting was associated with higher BMI Z-scores (BMIz) and waist-to-height ratio Z-scores (WHtRz) (N = 3819). Moreover, we observed functional connectivity of the nucleus accumbens to the cingulo-opercular, dorsal attention, fronto-parietal, salience and ventral attention networks were predictive of BMIz (N = 1817). Nucleus accumbens functional connectivity was not found to mediate the association between delay-discounting behaviour and BMIz. Delay discounting and nucleus accumbens functional connectivity are independently related to weight status in a large sample of early adolescents. A better understanding of the relationship between reward and overeating behaviours may better inform obesity interventions.

B - 65 Adolescent Cortico-Limbic Connectivity Mediates Associations between Internalizing Symptomology and Subsequent Neurocognitive Performance

Abstract Objective During development, internalizing symptoms negatively impact broad neurocognitive functioning. Hypoconnectivity between the Cingulo-Opercular network (CON) and limbic regions has been implicated in various psychiatric disorders. Here we attempt to investigate whether CON-limbic connectivity longitudinally mediates associations between internalizing behaviors and cognitive outcomes during adolescence. Method Internalizing symptoms were measured in 2668 youth (47% female) enrolled in the Adolescent Brain Cognitive Development study using the Child Behavior Checklist. Zero-order correlations were tested between baseline (ages 9–11) internalizing symptoms (anxiety, depression, somatic complaints) and performance on NIH Toolbox® neurocognitive measures at 4-year follow-up (ages 13–15). Significantly predicted tasks were included in a structural equation model (SEM), which tested whether a latent factor representing 2-year follow-up resting-state fMRI connectivity between the CON and limbic regions (i.e., bilateral hippocampus and amygdala) mediated associations between baseline internalizing symptoms and 4-year cognitive outcomes. Results Four neurocognitive tasks (Flanker, Picture Sequence, List Sorting, Pattern Comparison) regressed significantly onto at least one internalizing symptom. An SEM which tested the mediatory effects of CON-limbic connectivity on these associations fit the data well (CFI = 0.997; SRMR = 0.007; RMSEA =0.015 [0,0.027]). Increased anxiety and somatic symptoms significantly predicted reduced CON-limbic connectivity, while depression did not. Associations between anxiety and somatic symptoms and List Sorting performance were suppressed, indicating full mediation by CON-limbic connectivity on working memory. Connectivity also partially mediated a negative association between anxiety and Flanker performance. Conclusions Our findings point to CON-limbic hypoconnectivity as a potential mechanism underlying associations between late childhood internalizing symptoms and poorer executive functioning (most notably working memory) during early adolescence.

Cognitive benefits of higher cardiorespiratory fitness in preadolescent children are associated with increased connectivity within the cingulo-opercular network

Higher cardiorespiratory fitness has been associated with improved cognitive control in preadolescent children, with various studies highlighting related brain health benefits. This cross-sectional study aimed to provide novel insights into the fitness-cognition relationship by investigating task-related changes in effective connectivity within two brain networks involved in cognitive control: the cingulo-opercular and fronto-parietal networks. Twenty-four higher-fit and twenty-four lower-fit preadolescent children completed a modified flanker task that modulated inhibitory control demand while their EEG and task performance were concurrently recorded. Effective connectivity for correct trials in the theta band was estimated using directed transfer function. The results indicate that children with higher fitness levels demonstrated greater connectivity in specific directions within the cingulo-opercular network (average effect size, d = 0.72). Brain-behavior correlations demonstrated a positive association between the majority of these connections and general task accuracy, which was also higher in higher fit children (average correlation coefficient, ρ = 0.34). The findings further support a positive relationship between fitness and cognitive performance in children. EEG findings offer novel insights into the potential brain mechanisms underlying the fitness-cognition relationship. The study suggests that increased task-related connectivity within the cingulo-opercular network may mediate the cognitive benefits associated with higher fitness levels in preadolescent children.

The Contribution of Cognitive Control Networks in Word Selection Processing in Parkinson's Disease: Novel Insights from a Functional Connectivity Study.

Parkinson's disease (PD) patients are impaired in word production when the word has to be selected among competing alternatives requiring higher attentional resources. In PD, word selection processes are correlated with the structural integrity of the inferior frontal gyrus, which is critical for response selection, and the uncinate fasciculus, which is necessary for processing lexical information. In early PD, we investigated the role of the main cognitive large-scale networks, namely the salience network (SN), the central executive networks (CENs), and the default mode network (DMN), in word selection. Eighteen PD patients and sixteen healthy controls were required to derive nouns from verbs or generate verbs from nouns. Participants also underwent a resting-state functional MRI. Functional connectivity (FC) was examined using independent component analysis. Functional seeds for the SN, CENs, and DMN were defined as spheres, centered at the local activation maximum. Correlations were calculated between the FC of each functional seed and word production. A significant association between SN connectivity and task performance and, with less evidence, between CEN connectivity and the task requiring selection among a larger number of competitors, emerged in the PD group. These findings suggest the involvement of the SN and CEN in word selection in early PD, supporting the hypothesis of impaired executive control.

Functional Connectivity Profiles of Ten Sub-Regions within the Premotor and Supplementary Motor Areas: Insights into Neurophysiological Integration.

Objectives: This study aimed to comprehensively investigate the functional connectivity of ten sub-regions within the premotor and supplementary motor areas (Right and Left Premotor 6d1, 6d2, 6d3, and Right and Left pre-Supplementary Motor (presma) and SMA). Using advanced magnetic resonance imaging (MRI), the objective was to understand the neurophysiological integrative characteristics of these regions by examining their connectivity with eight distinct functional brain networks. While previous studies have largely treated these areas as homogeneous entities, there is a significant gap in our understanding of the specific roles and connectivity profiles of their distinct sub-regions. The goal was to uncover the roles of these regions beyond conventional motor functions, contributing to a more holistic understanding of brain functioning. Methods: The study involved 198 healthy volunteers, with the primary methodology being functional connectivity analysis using advanced MRI techniques. Ten sub-regions within the premotor and supplementary motor areas served as seed regions, and their connectivity with eight distinct brain regional functional networks, including the Sensorimotor, Dorsal Attention, Language, Frontoparietal, Default Mode, Cerebellar, Visual, and Salience networks, was investigated. This approach allowed for the exploration of synchronized activity between these critical brain areas, shedding light on their integrated functioning and relationships with other brain networks. Results: The study revealed a nuanced landscape of functional connectivity for the premotor and supplementary motor areas with the main functional brain networks. Despite their high functional connectedness within the motor network, these regions displayed diverse functional integrations with other networks. There was moderate connectivity with the Sensorimotor and Dorsal Attention networks, highlighting their roles in motor execution and attentional processes. However, connectivity with the Language, Frontoparietal, Default Mode, Cerebellar, Visual, and Salience networks was generally low, indicating a primary focus on motor-related tasks. Conclusions: This study emphasized the multifaceted roles of the sub-regions of the premotor and supplementary motor areas. Beyond their crucial involvement in motor functions, these regions exhibited varied functional integrations with different brain networks. The observed disparities, especially in the Sensorimotor and Dorsal Attention networks, indicated a nuanced and specialized involvement of these regions in diverse cognitive functions. By delineating the specific connectivity profiles of these sub-regions, this study addresses the existing knowledge gap and suggests unique and distinct roles for each brain area in sophisticated cognitive tasks beyond their conventional motor functions. The results suggested unique and distinct roles for each brain area in sophisticated cognitive tasks beyond their conventional motor functions. This study underscores the importance of considering the broader neurophysiological landscape to comprehend the intricate roles of these brain areas, contributing to ongoing efforts in unravelling the complexities of brain function.

Resting-state brain networks alterations in adolescents with Internet Gaming Disorder associate with cognitive control impairments.

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. 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. 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). 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.

Size and Topography of the Brain’s Functional Networks with Psychotic Experiences, Schizophrenia, and Bipolar Disorder

BackgroundExisting functional connectivity studies of psychosis use population-averaged functional network maps, despite highly variable topographies of these networks across the brain surface. We aimed to define the functional network areas and topographies in the general population and the changes associated with psychotic experiences (PEs) and disorders. MethodsMaps of 8 functional networks were generated using an individual-specific template-matching procedure for each participant from the Human Connectome Project Young Adult cohort (n = 1003) and from a matched case cohort (schizophrenia [SCZ], n = 27; bipolar disorder, n = 35) scanned identically with the same Connectom scanner. In the Human Connectome Project Young Adult cohort, PEs were estimated based on scores from the Achenbach Self-Report Scale. The relationship of symptoms to the probability of network representation at each cortical vertex was assessed using logistic regression. ResultsIn Human Connectome Project Young Adult participants, PE severity on the Achenbach thought problems scale was predicted by increased language network (LAN) and dorsal attention network (DAN) areas and decreased cingulo-opercular network area (r < 0.12). Significant effects were found in SCZ, with a larger DAN and LAN and a smaller frontoparietal network. Network pattern analysis in SCZ showed an increased probability of LAN in the posterior region of the left superior temporal gyrus and of the visual network in the left insula. Regression analyses in SCZ found that mood dysregulation was related to increased DAN surface area. ConclusionsThose with PEs and SCZ showed abnormal functional network cortical topographies, particularly involving DAN and LAN. Network findings may predict psychosis progression and guide earlier intervention.

Does practice make perfect? Functional connectivity of the salience network and somatosensory network predicts response to mind-body treatments for fibromyalgia.

Mind-body treatments can improve coping mechanisms to deal with pain, improve the quality of life of patients with fibromyalgia syndrome (FMS), and reduce perceived pain in some cases. However, responses to these treatments are highly variable, the mechanisms underpinning them remain unclear, and reliable predictors of treatment response are lacking. We employed resting-state blood oxygen level-dependent (rsBOLD) functional magnetic resonance imaging (fMRI) to examine changes in brain functional connectivity (FC) following mind-body treatment that may relate to and predict pain relief. We recruited patients with FMS who underwent either mindfulness-based stress reduction (MBSR; n = 18) or a psychoeducational program (FibroQoL; n = 22) and a treatment-as-usual FMS group (TAU; n = 18). We collected rsBOLD data, alongside subjective pain, anxiety, depression, and catastrophizing measures prior to and following treatments. We examined behavioral changes and FC changes in the salience network (SN) and sensorimotor network (SMN) and performed regression analyses to identify predictors for treatment response. The MBSR and FibroQoL groups experienced significant reductions in pain catastrophizing. After treatment, the FC of the sensorimotor cortex with the rest of the SMN became significantly reduced in the MBSR group compared to the TAU group. The FC between the SN and the SMN at baseline was negatively correlated with pain reductions following MBSR but positively correlated with pain reductions in the FibroQoL group. These results yielded large to very large effect sizes. Following MBSR, only for those patients with lower baseline SMN-SN FC, minutes of mindfulness practice were positively associated with clinical improvement (small to medium effect size). Different mind-body treatments are underpinned by discrete brain networks. Measures of the functional interplay between SN and SMN have the potential as predictors of mind-body treatment response in patients with FMS.

Enhanced diversity on connector hubs following sleep deprivation: Evidence from diffusion and functional magnetic resonance imaging

Sleep deprivation has been demonstrated to exert widespread and intricate impacts on the brain network. The human brain network is a modular network composed of interconnected nodes. This network consists of provincial hubs and connector hubs, with provincial hubs having diverse connectivities within their own modules, while connector hubs distribute their connectivities across different modules. The latter is crucial for integrating information from various modules and ensuring the normal functioning of the modular brain. However, there has been a lack of systematic investigation into the impact of sleep deprivation on brain connector hubs. In this study, we utilized functional connectivity from resting-state functional magnetic resonance imaging, as well as structural connectivity from diffusion-weighted imaging, to systematically explore the variation of connector hub properties in the cerebral cortex after one night of sleep deprivation. The normalized participation coefficients (PCnorm) were utilized to identify connector hubs. In both the functional and structural networks, connector hubs exhibited a significant increase in average PCnorm, indicating the diversity enhancement of the connector hub following sleep deprivation. This enhancement is associated with increased network cost, reduced modularity, and decreased small-worldness, but enhanced global efficiency. This may potentially signify a compensatory mechanism within the brain following sleep deprivation. The significantly affected connector hubs were primarily observed in both the Control Network and Salience Network. We believe that the observed results reflect the increasing demand on the brain to invest more effort at preventing performance deterioration after sleep loss, in exchange for increased communication efficiency, especially involving systems responsible for neural resource allocation and cognitive control. These results have been replicated in an independent dataset. In conclusion, this study has enhanced our understanding of the compensatory mechanism in the brain response to sleep deprivation. This compensation is characterized by an enhancement in the connector hubs responsible for inter-modular communication, especially those related to neural resource and cognitive control. As a result, this compensation comes with a higher network cost but leads to an improvement in global communication efficiency, akin to a more random-like network manner.

Frontostriatal salience network expansion in individuals in depression

Decades of neuroimaging studies have shown modest differences in brain structure and connectivity in depression, hindering mechanistic insights or the identification of risk factors for disease onset1. Furthermore, whereas depression is episodic, few longitudinal neuroimaging studies exist, limiting understanding of mechanisms that drive mood-state transitions. The emerging field of precision functional mapping has used densely sampled longitudinal neuroimaging data to show behaviourally meaningful differences in brain network topography and connectivity between and in healthy individuals2–4, but this approach has not been applied in depression. Here, using precision functional mapping and several samples of deeply sampled individuals, we found that the frontostriatal salience network is expanded nearly twofold in the cortex of most individuals with depression. This effect was replicable in several samples and caused primarily by network border shifts, with three distinct modes of encroachment occurring in different individuals. Salience network expansion was stable over time, unaffected by mood state and detectable in children before the onset of depression later in adolescence. Longitudinal analyses of individuals scanned up to 62 times over 1.5 years identified connectivity changes in frontostriatal circuits that tracked fluctuations in specific symptoms and predicted future anhedonia symptoms. Together, these findings identify a trait-like brain network topology that may confer risk for depression and mood-state-dependent connectivity changes in frontostriatal circuits that predict the emergence and remission of depressive symptoms over time.

Whole-brain mechanism of neurofeedback therapy: predictive modeling of neurofeedback outcomes on repetitive negative thinking in depression

Real-time fMRI neurofeedback (rtfMRI-NF) has emerged as a promising intervention for psychiatric disorders, yet its clinical efficacy remains underexplored due to an incomplete mechanistic understanding. This study aimed to delineate the whole-brain mechanisms underpinning the effects of rtfMRI-NF on repetitive negative thinking in depression. In a double-blind randomized controlled trial, forty-three depressed individuals underwent NF training targeting the functional connectivity (FC) between the posterior cingulate cortex and the right temporoparietal junction, linked to rumination severity. Participants were randomly assigned to active or sham groups, with the sham group receiving synthesized feedback mimicking real NF signal patterns. The active group demonstrated a significant reduction in brooding rumination scores (d = −1.52, p < 0.001), whereas the sham group did not (d = −0.23, p = 0.503). While the target FC did not show discernible training effects or group differences, connectome-based predictive modeling (CPM) analysis revealed that the interaction between brain activity during regulation and brain response to the feedback signal was the critical factor in explaining treatment outcomes. The model incorporating this interaction successfully predicted rumination changes across both groups. The FCs significantly contributing to the prediction were distributed across brain regions, notably the frontal control, salience network, and subcortical reward processing areas. These results underscore the importance of considering the interplay between brain regulation activities and brain response to the feedback signal in understanding the therapeutic mechanisms of rtfMRI-NF. The study affirms rtfMRI-NF’s potential as a therapeutic intervention for repetitive negative thinking and highlights the need for a nuanced understanding of the whole-brain mechanisms contributing to its efficacy.

Eight brain structures mediate the age-related alterations of the working memory: forward and backward digit span tasks.

Working memory (WM) as one of the executive functions is an essential neurocognitive ability for daily life. Findings have suggested that aging is often associated with working memory and neural decline, but the brain structures and resting-state brain networks that mediate age-related differences in WM remain unclear. A sample consisting of 252 healthy participants in the age range of 20 to 70years was used. Several cognitive tasks, including the n-back task and the forward and backward digit span tests were used. Also, resting-state functional imaging, as well as structural imaging using a 3T MRI scanner, were performed, resulting in 85 gray matter volumes and five resting-state networks, namely the anterior and posterior default mode, the right and left executive control, and the salience networks. Also, mediation analyses were used to investigate the role of gray matter volumes and resting-state networks in the relationship between age and WM. Behaviorally, aging was associated with decreased performance in the digit span task. Also, aging was associated with a decreased gray matter volume in 80 brain regions, and with a decreased activity in the anterior default mode network, executive control, and salience networks. Importantly, the path analysis showed that the GMV of the medial orbitofrontal, precentral, parieto-occipital, amygdala, middle occipital, posterior cingulate, and thalamus areas mediated the age-related differences in the forward digit span task, and the GMV of superior temporal gyrus mediated the age-related differences in the backward digit span task. This study identified the brain structures mediating the relationship between age and working memory, and we hope that our research provides an opportunity for early detection of individuals at risk of age-related memory decline.

Provincial and connector qualities of somatosensory brain network hubs in bipolar disorder.

Brain network hubs are highly connected brain regions serving as important relay stations for information integration. Recent studies have linked mental disorders to impaired hub function. Provincial hubs mainly integrate information within their own brain network, while connector hubs share information between different brain networks. This study used a novel time-varying analysis to investigate whether hubs aberrantly follow the trajectory of other brain networks than their own. The aim was to characterize brain hub functioning in clinically remitted bipolar patients. We analyzed resting-state functional magnetic resonance imaging data from 96 euthymic individuals with bipolar disorder and 61 healthy control individuals. We characterized different hub qualities within the somatomotor network. We found that the somatomotor network comprised mainly provincial hubs in healthy controls. Conversely, in bipolar disorder patients, hubs in the primary somatosensory cortex displayed weaker provincial and stronger connector hub function. Furthermore, hubs in bipolar disorder showed weaker allegiances with their own brain network and followed the trajectories of the limbic, salience, dorsal attention, and frontoparietal network. We suggest that these hub aberrancies contribute to previously shown functional connectivity alterations in bipolar disorder and may thus constitute the neural substrate to persistently impaired sensory integration despite clinical remission.

The Interaction Effects of Sex, Age, APOE and Common Health Risk Factors on Human Brain Functions.

Nonlinear changes in brain function during aging are shaped by a complex interplay of factors, including sex, age, genetics, and modifiable health risk factors. However, the combined effects and underlying mechanisms of these factors on brain functional connectivity remain poorly understood. To comprehensively investigate the combined associations of sex, age, APOE genotypes, and ten common modifiable health risk factors with brain functional connectivities during aging. This analysis used data from 36,630 UK Biobank participants, aged 44-81, who were assessed for sex, age, APOE genotypes, 10 health risk factors, and brain functional connectivities through resting-state functional magnetic resonance imaging. Brain functional connectivities were evaluated through within- and between-network functional connectivities and connectivity strength. Associations between risk factors and brain functional connectivities, including their interaction effects, were analyzed. Hypertension, BMI, and education were the top three influential factors. Sex-specific effects were also observed in interactions involving APOE4 gene, smoking, alcohol consumption, diabetes, BMI, and education. Notably, a negative sex-excessive alcohol interaction showed a stronger negative effect on functional connectivities in males, particularly between the dorsal attention network and the language network, while moderate alcohol consumption appeared to have protective effects. A significant negative interaction between sex and APOE4 revealed a greater reduction in functional connectivity between the cingulo-opercular network and the posterior multimodal network in male APOE4 carriers. Additional findings included a negative age-BMI interaction between the visual and dorsal attention networks, and a positive age-hypertension interaction between the frontoparietal and default mode networks. The findings highlight significant sex disparities in the associations between age, the APOE-ε4 gene, modifiable health risk factors, and brain functional connectivity, emphasizing the necessity of jointly considering these factors to gain a deeper understanding of the complex processes underlying brain aging.