Within-network Functional Connectivity Research Articles

A Subset of Cortical Areas Exhibit Adult-like Functional Network Patterns in Early Childhood.

The human cerebral cortex contains groups of areas that support sensory, motor, cognitive, and affective functions, often categorized into functional networks. These networks show stronger internal and weaker external functional connectivity (FC), with FC profiles more similar within the same network. Previous studies have shown these networks develop from nascent forms before birth to their mature, adult-like structures in childhood. However, these analyses often rely on adult functional network definitions. This study assesses the potential misidentification of infant functional networks when using adult models and explores the consequences and possible solutions to this problem. Our findings suggest that although adult networks only marginally describe infant FC organization better than chance, misidentification is primarily driven by specific areas. Restricting functional networks to areas with adult-like network clustering revealed consistent within-network FC across scans and throughout development. These areas are also near locations with low network identity variability. Our results highlight the implications of using adult networks for infants and offer guidance for selecting and utilizing functional network models based on research questions and scenarios.

Changes in resting-state functional connectivity of large-scale brain networks in bulimia nervosa: evidence from causal analysis.

Bulimia nervosa (BN) has been observationally linked to the functional connectivity (FC) of large-scale brain networks, but the biological mechanisms remain unclear. This study used two-sample Mendelian randomization (MR) with genetic variations as instrumental variables (IVs) to explore potential causal relationships between FC and BN. Summary data from genome-wide association studies (GWAS) involving 2,564 individuals were analyzed to identify genetically predicted BN. Functional magnetic resonance imaging parameters and materials were sourced from the UK Biobank. The variables underwent independent component analysis processing by the database to generate the final GWAS dataset. Various methods, including MR Pleiotropy RESidual Sum and Outlier, MR Egger, and weighted median, were employed to detect heterogeneity and pleiotropy, with inverse variance weighting serving as the principal estimation method (P < 0.05). The FC imaging-derived phenotypes revealed that BN exerted a causal influence on the FC between large-scale networks, including the visual network, default mode network (DMN), frontoparietal network, somatosensory network (SSN), and ventral attention network. Additionally, BN had a causal impact on the within-network FC of both the DMN and SSN. The study provides evidence that BN leads to further changes in FC patterns within and between large-scale brain networks.

SuperAging functional connectomics from resting-state functional MRI.

Understanding the relationship between functional connectivity (FC) of higher-order neurocognitive networks and age-related cognitive decline is a complex and evolving field of research. Decreases in FC have been associated with cognitive decline in persons with Alzheimer's disease and related dementias (ADRD). However, the contributions of FC have been less straightforward in typical cognitive aging. Some investigations suggest relatively robust FC within neurocognitive networks differentiates unusually successful cognitive aging from average aging, while others do not. Methodologic limitations in data processing and varying definitions of 'successful aging' may have contributed to the inconsistent results to date. The current study seeks to address previous limitations by optimized MRI methods to examine FC in the well-established SuperAging phenotype, defined by age and cognitive performance as individuals 80 and older with episodic memory performance equal to or better than 50-to-60-year-olds. Within- and between-network FC of large-scale neurocognitive networks were compared between 24 SuperAgers and 16 cognitively average older-aged control (OACs) with stable cognitive profiles using resting-state functional MRI (rs-fMRI) from a single visit. Group classification was determined based on measures of episodic memory, executive functioning, verbal fluency and picture naming. Inclusion criteria required stable cognitive status across two visits. First, we investigated the FC within and between seven resting-state networks from a common atlas parcellation. A separate index of network segregation was also compared between groups. Second, we investigated the FC between six subcomponents of the default mode network (DMN), the neurocognitive network commonly associated with memory performance and disrupted in persons with ADRD. For each analysis, FCs were compared across groups using two-sample independent t-tests and corrected for multiple comparisons. There were no significant between-group differences in demographic characteristics including age, sex and education. At the group-level, within-network FC, between-network FC, and segregation measurements of seven large-scale networks, including subcomponents of the DMN, were not a primary differentiator between cognitively average aging and SuperAging phenotypes. Thus, FC within or between large-scale networks does not appear to be a primary driver of the exceptional memory performance observed in SuperAgers. These results have relevance for differentiating the role of FC changes associated with cognitive aging from those associated with ADRD.

Central autonomic network dysfunction and plasma Alzheimer’s disease biomarkers in older adults

BackgroundHigher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer’s disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults.MethodsIndependently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aβ42, Aβ40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed.ResultsAll autonomic networks were positively associated with Aβ42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected.ConclusionThe present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aβ42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.

Functional connectivity is linked to working memory differences in children with reading learning disability

Reading learning disability (RLD) is characterized by a specific difficulty in learning to read that is not better explained by an intellectual disability, lack of instruction, psychosocial adversity, or a neurological disorder. According to the domain-general hypothesis, a working memory deficit is the primary problem. Working memory in this population has recently been linked to altered resting-state functional connectivity within the default mode network (DMN), salience network (SN), and frontoparietal network (FPN) compared to that in typically developing individuals. The main purpose of the present study was to compare the within-network functional connectivity of the DMN, SN, FPN, and reading network in two groups of children with RLD: a group with lower-than-average working memory (LWM) and a group with average working memory (AWM). All subjects underwent resting-state functional magnetic resonance imaging (fMRI), and data were analyzed from a network perspective using the network brain statistics framework. The results showed that the LWM group had significantly weaker connectivity in a network that involved brain regions in the DMN, SN, and FPN than the AWM group. Although there was no significant difference between groups in reading network in the present study, other studies have shown relationship of the connectivity of the angular gyrus, supramarginal gyrus, and inferior parietal lobe with the phonological process of reading. The results suggest that although there are significant differences in functional connectivity in the associated networks between children with LWM and AWM, the distinctive cognitive profile has no specific effect on the reading network.

405. Exploring the Glutamatergic Underpinnings of Within-Network Functional Connectivity and Motor Performance in a Transdiagnostic Cohort

405. Exploring the Glutamatergic Underpinnings of Within-Network Functional Connectivity and Motor Performance in a Transdiagnostic Cohort

Differences between subclinical attention-deficit/hyperactivity and autistic traits in default mode, salience, and frontoparietal network connectivities in young adult Japanese

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are associated with attentional impairments, with both commonalities and differences in the nature of their attention deficits. This study aimed to investigate the neural correlates of ADHD and ASD traits in healthy individuals, focusing on the functional connectivity (FC) of attention-related large-scale brain networks (LSBNs). The participants were 61 healthy individuals (30 men; age, 21.9 ± 1.9 years). The Adult ADHD Self-Report Scale (ASRS) and Autism Spectrum Quotient (AQ) were administered as indicators of ADHD and ASD traits, respectively. Performance in the continuous performance test (CPT) was used as a behavioural measure of sustained attentional function. Functional magnetic resonance imaging scans were performed during the resting state (Rest) and auditory oddball task (Odd). Considering the critical role in attention processing, we focused our analyses on the default mode (DMN), frontoparietal (FPN), and salience (SN) networks. Region of interest (ROI)-to-ROI analyses (false discovery rate < 0.05) were performed to determine relationships between psychological measures with within-network FC (DMN, FPN, and SN) as well as with between-network FC (DMN-FPN, DMN-SN, and FPN-SN). ASRS scores, but not AQ scores, were correlated with less frequent commission errors and shorter reaction times in the CPT. During Odd, significant positive correlations with ASRS were demonstrated in multiple FCs within DMN, while significant positive correlations with AQ were demonstrated in multiple FCs within FPN. AQs were negatively correlated with FPN-SN FCs. During Rest, AQs were negatively and positively correlated with one FC within the SN and multiple FCs between the DMN and SN, respectively. These findings of the ROI-to-ROI analysis were only partially replicated in a split-half replication analysis, a replication analysis with open-access data sets, and a replication analysis with a structure-based atlas. The better CPT performance by individuals with subclinical ADHD traits suggests positive effects of these traits on sustained attention. Differential associations between LSBN FCs and ASD/ADHD traits corroborate the notion of differences in sustained and selective attention between clinical ADHD and ASD.

P01.01.A THE IMPACT OF BRAIN LESIONS ON HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH WHO CNS GRADE 3 OR 4 GLIOMA: A LESION-FUNCTION AND RESTING-STATE FMRI ANALYSIS

Abstract BACKGROUND In glioma patients, tumor development and multimodality therapy are associated with changes in health-related quality of life (HRQoL). It is largely unknown how different types and locations of tumor- and treatment-related brain lesions, as well as their relationship to white matter tracts and functional brain networks, affect HRQoL. MATERIAL AND METHODS In 121 patients with pretreated gliomas of WHO CNS grades 3 or 4, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET, resting-state functional MRI (rs-fMRI) and self-reported HRQoL questionnaires (EORTC QLQ-C30/BN20) were obtained. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and lesions with pathologically increased FET uptake were delineated. Effects of tumor lateralization, involvement of white matter tracts or resting-state network nodes by different types of lesions and within-network rs-fMRI connectivity were analyzed in terms of their interaction with HRQoL scores. RESULTS Right hemisphere gliomas were associated with significantly less favorable outcomes in physical, role, emotional and social functioning, compared with left-sided tumors. Most functional HRQoL scores correlated significantly with right-sided white-matter tracts involvement by T2/FLAIR hyperintensities and with loss of within-network functional connectivity of right-sided nodes. Tumors of the left hemisphere caused significantly more communication deficits. CONCLUSION In pretreated high-grade gliomas, right hemisphere lesions are associated with reduced HRQoL scores in most functional domains except communication ability, compared to tumors of the left hemisphere. These relationships are mainly observed for T2/FLAIR lesions involving structural and functional networks in the right hemisphere. The data suggest that sparing the right hemisphere from treatment-related tissue damage may improve HRQoL in glioma patients.

Functional connectivity mediates the relationship between cardiorespiratory fitness and stress in midlife.

BackgroundIncreasing evidence suggests that the relation between mental health and physical health is bidirectional and underpinned by complex neural systems. Cardiovascular fitness is a key measure of physical health but its relation to mental health is insufficiently examined. Characterizing the neural mechanisms by which cardiovascular fitness influences mental health could inform the development of strategies to promote mental health and minimize the risk of mental disorders. Methods and resultsThe relation between cardiorespiratory fitness, functional brain connectivity and mental health was studied in 418 healthy middle-aged (aged 40–65 years) adult participants of the Barcelona Brain Health Initiative (BBHI). Higher cardiorespiratory fitness, measured by VO₂ peak, was associated with lower symptoms of anxiety (β = −0.111, p = 0.017) and stress (β = −0.242, p = 0.002) scores, evaluated by the Depression Anxiety and Stress Scale (DASS-21) and its three subscales (stress, anxiety, and depression). Higher within-network functional connectivity of the Default Mode Network (DMN) was associated with higher VO₂ peak (β = 0.195, p = 0.002), and lower stress scores (β = −0.126, p = 0.011). In addition, higher functional connectivity between the Frontoparietal Network (FPN) and Salience Network (SN) was associated with higher VO₂ peak (β = 0.187, p = 0.002), and lower stress scores (β = −0.123, p = 0.016). Both within-DMN [ACME = −0.02 (-0.04,-0.00), p = 0.040] and between FPN-SN [ACME = −0.01 (-0.04,-0.00), p = 0.036] functional connectivity mediated the relationship between cardiorespiratory fitness and stress. ConclusionsThe relationship between the cardiorespiratory fitness and stress in middle-aged adults is mediated by functional connectivity of several intrinsic resting-state networks. These results highlight a potential mechanistic pathway through which higher cardiorespiratory fitness can positively impact brain health in midlife.

Impaired large-scale cortico-hippocampal network connectivity, including the anterior temporal and posterior medial systems, and its associations with cognition in patients with first-episode schizophrenia.

The cortico-hippocampal network is an emerging neural framework with striking evidence that it supports cognition in humans, especially memory; this network includes the anterior temporal (AT) system, the posterior medial (PM) system, the anterior hippocampus (aHIPPO), and the posterior hippocampus (pHIPPO). This study aimed to detect aberrant patterns of functional connectivity within and between large-scale cortico-hippocampal networks in first-episode schizophrenia patients compared with a healthy control group via resting-state functional magnetic resonance imaging (rs-fMRI) and to explore the correlations of these aberrant patterns with cognition. A total of 86 first-episode, drug-naïve schizophrenia patients and 102 healthy controls (HC) were recruited to undergo rs-fMRI examinations and clinical evaluations. We conducted large-scale edge-based network analysis to characterize the functional architecture of the cortico-hippocampus network and investigate between-group differences in within/between-network functional connectivity. Additionally, we explored the associations of functional connectivity (FC) abnormalities with clinical characteristics, including scores on the Positive and Negative Syndrome Scale (PANSS) and cognitive scores. Compared with the HC group, schizophrenia patients exhibited widespread alterations to within-network FC of the cortico-hippocampal network, with decreases in FC involving the precuneus (PREC), amygdala (AMYG), parahippocampal cortex (PHC), orbitofrontal cortex (OFC), perirhinal cortex (PRC), retrosplenial cortex (RSC), posterior cingulate cortex (PCC), angular gyrus (ANG), aHIPPO, and pHIPPO. Schizophrenia patients also showed abnormalities in large-scale between-network FC of the cortico-hippocampal network, in the form of significantly decreased FC between the AT and the PM, the AT and the aHIPPO, the PM and the aHIPPO, and the aHIPPO and the pHIPPO. A number of these signatures of aberrant FC were correlated with PANSS score (positive, negative, and total score) and with scores on cognitive test battery items, including attention/vigilance (AV), working memory (WM), verbal learning and memory (Verb_Lrng), visual learning and memory (Vis_Lrng), reasoning and problem-solving (RPS), and social cognition (SC). Schizophrenia patients show distinct patterns of functional integration and separation both within and between large-scale cortico-hippocampal networks, reflecting a network imbalance of the hippocampal long axis with the AT and PM systems, which regulate cognitive domains (mainly Vis_Lrng, Verb_Lrng, WM, and RPS), and particularly involving alterations to FC of the AT system and the aHIPPO. These findings provide new insights into the neurofunctional markers of schizophrenia.

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India

Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their underlying brain mechanisms. This multicenter population-based cohort study analyzed cross-sectional data of the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, recruited between November 4, 2016, and May 4, 2019. Participants aged 6 to 23 years were characterized using deep phenotyping measures of behavior, neuropsychology, psychopathology, brain neuroimaging, and exposure to developmental adversities and environmental neurotoxins. All analyses were performed between June 1, 2020, and December 31, 2021. Arsenic levels were measured in urine as an index of exposure. Executive function measured using the cVEDA neuropsychological battery, gray matter volume (GMV) from T1-weighted magnetic resonance imaging, and functional network connectivity measures from resting state functional magnetic resonance imaging. A total of 1014 participants aged 6 to 23 years (589 male [58.1%]; mean [SD] age, 14.86 [4.79] years) were included from 5 geographic locations. Sparse-partial least squares analysis was used to describe a negative association of arsenic exposure with executive function (r = -0.12 [P = 5.4 × 10-4]), brain structure (r = -0.20 [P = 1.8 × 10-8]), and functional connectivity (within network, r = -0.12 [P = 7.5 × 10-4]; between network, r = -0.23 [P = 1.8 × 10-10]). Alterations in executive function were partially mediated by GMV (b = -0.004 [95% CI, -0.007 to -0.002]) and within-network functional connectivity (b = -0.004 [95% CI, -0.008 to -0.002]). Socioeconomic status and body mass index moderated the association between arsenic and GMV, such that the association was strongest in participants with lower socioeconomic status and body mass index. The findings of this cross-sectional study suggest that low-level arsenic exposure was associated with alterations in executive functioning and underlying brain correlates. These results indicate potential detrimental consequences of arsenic exposure that are below the currently recommended guidelines and may extend beyond endemic risk areas. Precision medicine approaches to study global mental health vulnerabilities highlight widespread but potentially modifiable risk factors and a mechanistic understanding of the impact of low-level arsenic exposure on brain development.

Altered neural associations with cognitive and emotional functions in cannabis dependence.

Negative emotional state has been found to correlate with poor cognitive performance in cannabis-dependent (CD) individuals, but not healthy controls (HCs). To examine the neural substrates underlying such unusual emotion-cognition coupling, we analyzed the behavioral and resting state fMRI data from the Human Connectome Project and found opposite brain-behavior associations in the CD and HC groups: (i) although the cognitive performance was positively correlated with the within-network functional connectivity strength and segregation (i.e. clustering coefficient and local efficiency) of the cognitive network in HCs, these correlations were inversed in CDs; (ii) although the cognitive performance was positively correlated with the within-network Granger effective connectivity strength and integration (i.e. characteristic path length) of the cognitive network in CDs, such associations were not significant in HCs. In addition, we also found that the effective connectivity strength within cognition network mediated the behavioral coupling between emotional state and cognitive performance. These results indicate a disorganization of the cognition network in CDs, and may help improve our understanding of substance use disorder.

Age-related learning difficulty through trial-and-error method associated with decreased default mode network integration in healthy middle-aged adults

ABSTRACT Introduction Efficient learning is critical to adapting to different environments. There are well-known learning principles in cognitive rehabilitation, including errorless (EL) and trial-and-error (T&E) learning; however, little is known about their underlying neural mechanisms. In the current study, to understand the age-related changes in learning benefits and neural mechanisms applying EL and T&E learning methods in healthy middle-aged adults, we conducted a graph theoretical analysis using functional magnetic resonance imaging data and analyzed the relationship between learning benefits and age, as well as functional network connectivity and age, with both learning principles. Method A total of 43 participants performed a color-name association task through EL and T&E learning methods. We focused on the functional connectivity patterns of the default mode network (DMN) since previous studies demonstrated this network to be more distinctive and important for the T&E learning method than EL. Within-network functional connectivity was used as the graph metric. Results Age showed significant moderate negative correlations with T&E scores and within-DMN functional connectivity in the test state following T&E learning. Conversely, age was not significantly correlated with EL scores or within-DMN functional connectivity in either the EL learning or test states. Conclusions Our findings demonstrate the age-related learning decline associated with decreased DMN integration with aging, when applying the T&E method but not the EL method, even in healthy middle-aged adults. Relationships between the underlying neural network and age are different depending on the learning method. This suggests the need to take into consideration the remaining learning ability through the T&E learning method compared to normal aging and to utilize residual DMN functioning, in addition to the comparison between score differences between EL and T&E methods, when tailoring an individual learning approach.

Classical and non-classical psychedelic drugs induce common network changes in human cortex

The neurobiology of the psychedelic experience is not fully understood. Identifying common brain network changes induced by both classical (i.e., acting at the 5-HT2 receptor) and non-classical psychedelics would provide mechanistic insight into state-specific characteristics. We analyzed whole-brain functional connectivity based on resting-state fMRI data in humans, acquired before and during the administration of nitrous oxide, ketamine, and lysergic acid diethylamide. We report that, despite distinct molecular mechanisms and modes of delivery, all three psychedelics reduced within-network functional connectivity and enhanced between-network functional connectivity. More specifically, all three drugs increased connectivity between right temporoparietal junction and bilateral intraparietal sulcus as well as between precuneus and left intraparietal sulcus. These regions fall within the posterior cortical “hot zone,” posited to mediate the qualitative aspects of experience. Thus, both classical and non-classical psychedelics modulate networks within an area of known relevance for consciousness, identifying a biologically plausible candidate for their subjective effects.

Creative thinking and brain network development in schoolchildren.

Fostering creative minds has always been a premise to ensure adaptation to new challenges of human civilization. While some alternative educational settings (i.e., Montessori) were shown to nurture creative skills, it is unknown how they impact underlying brain mechanisms across the school years. This study assessed creative thinking and resting-state functional connectivity via fMRI in 75 children (4-18 y.o.) enrolled either in Montessori or traditional schools. We found that pedagogy significantly influenced creative performance and underlying brain networks. Replicating past work, Montessori-schooled children showed higher scores on creative thinking tests. Using static functional connectivity analysis, we found that Montessori-schooled children showed decreased within-network functional connectivity of the salience network. Moreover, using dynamic functional connectivity, we found that traditionally-schooled children spent more time in a brain state characterized by high intra-default mode network connectivity. These findings suggest that pedagogy may influence brain networks relevant to creative thinking-particularly the default and salience networks. Further research is needed, like a longitudinal study, to verify these results given the implications for educational practitioners. RESEARCH HIGHLIGHTS: Most executive jobs are prospected to be obsolete within several decades, so creative skills are seen as essential for the near future. School experience has been shown to play a role in creativity development, however, the underlying brain mechanisms remained under-investigated yet. Seventy-five 4-18 years-old children, from Montessori or traditional schools, performed a creativity task at the behavioral level, and a 6-min resting-state MR scan. We uniquely report preliminary evidence for the impact of pedagogy on functional brain networks.

Transdiagnostic and Disorder-Specific Resting-State Functional Network Alterations in Alcohol Use Disorder, Schizophrenia, Bipolar Affective Disorder and Obsessive-Compulsive Disorder

Introduction The ICD and DSM diagnostic categories do not represent entirely distinct entities because several cognitive impairments are shared across psychiatric disorders. Such shared cognitive impairments are hypothesized to be caused by common neurobiological substrates, one of which is transdiagnostic alterations in functional network connectivity (FNC). Objectives To investigate and compare the within-network functional connectivity (WNFC) and between-network functional connectivity (BNFC) in alcohol use disorder (AUD), schizophrenia (SCZ), bipolar affective disorder (BPAD), obsessive-compulsive disorder (OCD) and healthy controls (HC) using resting-state fMRI employing a data-driven exploratory approach. Methods The current study was a secondary analysis of data from the ADBS project in India. After pre-processing of fMRI data, a spatially and temporally constrained group-independent component analysis in the GIFT toolbox was performed using the NeuroMark templates to generate 53 independent components (ICs). These components were divided into seven functional domains including subcortical (SC), auditory (AU), sensorimotor (SM), visual (VI), cognitive-control (CC), default-mode (DM), and cerebellar (CB). To investigate the FNC correlations associated with group status (patients or HC) univariate models were applied which were subjected to corrections for multiple comparisons at an alpha=0.05 significance level using the FDR. Results The overall sample size was 249 [AUD=35, SCZ=44, BPAD=48, OCD=53, and HC=69]. Transdiagnostic WNFC alterations largely involved dysconnectivity in the CC, DM, and SC domains, resulting in ICs with both increased and decreased WNFC. Transdiagnostic BNFC alterations were primarily in the form of increased connectivity of the SC domain with various cortical domains whereas reduced connectivity was noted between AU, VI, SM, and CB domains. There was AUD-specific hyperconnectivity in the CC domain and SCZ-specific hyperconnectivity in the DM domain, and dysconnectivity in the SC domain. BPAD-specific hyperconnectivity was identified in DM and SC domains in addition to increased connectivity between CB and SM domains and decreased connectivity between CB and SC domains. All results were significant at p ≤ 0.05; [FDR] q= 0.05. Conclusions Our transdiagnostic WNFC alterations corresponded to the central executive network, default mode network, salience network, and CSTC loop, which provided transdiagnostic evidence for the triple network model of psychopathology and underlined the relevance of subcortical dysconnectivity in this model. Furthermore, our BNFC changes showed subcortical hyperconnectivity with many cortical networks, underscoring its relevance as a potential target for transdiagnostic therapeutic interventions. Disclosure of Interest None Declared

The impact of brain lesions on health-related quality of life in patients with WHO CNS grade 3 or 4 glioma: a lesion-function and resting-state fMRI analysis

PurposeIn glioma patients, tumor development and multimodality therapy are associated with changes in health-related quality of life (HRQoL). It is largely unknown how different types and locations of tumor- and treatment-related brain lesions, as well as their relationship to white matter tracts and functional brain networks, affect HRQoL.MethodsIn 121 patients with pretreated gliomas of WHO CNS grades 3 or 4, structural MRI, O-(2-[18F]fluoroethyl)-L-tyrosine (FET) PET, resting-state functional MRI (rs-fMRI) and self-reported HRQoL questionnaires (EORTC QLQ-C30/BN20) were obtained. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and lesions with pathologically increased FET uptake were delineated. Effects of tumor lateralization, involvement of white matter tracts or resting-state network nodes by different types of lesions and within-network rs-fMRI connectivity were analyzed in terms of their interaction with HRQoL scores.ResultsRight hemisphere gliomas were associated with significantly less favorable outcomes in physical, role, emotional and social functioning, compared with left-sided tumors. Most functional HRQoL scores correlated significantly with right-sided white-matter tracts involvement by T2/FLAIR hyperintensities and with loss of within-network functional connectivity of right-sided nodes. Tumors of the left hemisphere caused significantly more communication deficits.ConclusionIn pretreated high-grade gliomas, right hemisphere lesions are associated with reduced HRQoL scores in most functional domains except communication ability, compared to tumors of the left hemisphere. These relationships are mainly observed for T2/FLAIR lesions involving structural and functional networks in the right hemisphere. The data suggest that sparing the right hemisphere from treatment-related tissue damage may improve HRQoL in glioma patients.

Reduced Segregation of Brain Networks in Spatial Neglect After Stroke.

Background/Purpose: To investigate the association between the degree of spatial neglect and the changes of brain system segregation (SyS; i.e., the ratio of the extent to which brain networks interact internally and with each other) after stroke. Methods: A cohort of 20 patients with right hemisphere lesion was submitted to neuropsychological assessment as well as to resting-state functional magnetic resonance imaging session at acute stage after stroke. The severity of spatial neglect was quantified using the Center of Cancellation (CoC) scores of the Bells cancellation test. For each patient, resting-state functional connectivity (FC) matrices were assessed by implementing a brain parcellation of nine networks that included the visual network, dorsal attention network (DAN), ventral attention network (VAN), sensorimotor network (SMN), auditory network, cingulo-opercular network, language network, frontoparietal network, and default mode network (DMN). For each patient and each network, we then computed the SyS derived by subtracting the between-network FC from the within-network FC (normalized by the within-network FC). Finally, for each network, the CoC scores were correlated with the SyS. Results: The correlational analyses indicated a negative association between CoC and SyS in the DAN, VAN, SMN, and DMN (q < 0.05 false discovery rate [FDR]-corrected). Patients with more severe spatial neglect exhibited lower SyS and vice versa. Conclusion: The loss of segregation in multiple and specific networks provides a functional framework for the deficits in spatial and nonspatial attention and motor/exploratory ability observed in neglect patients.

Cognitive efficacy and neural mechanisms of music-based neurological rehabilitation for traumatic brain injury.

Traumatic brain injury (TBI) causes lifelong cognitive deficits, most often in executive function (EF). Both musical training and music-based rehabilitation have been shown to enhance EF and neuroplasticity. Thus far, however, there is little evidence for the potential rehabilitative effects of music for TBI. Here, we review the core findings from our recent cross-over randomized controlled trial in which a 10-week music-based neurological rehabilitation (MBNR) protocol was administered to 40 patients with moderate-to-severe TBI. Neuropsychological testing and structural/functional magnetic resonance imaging were collected at three time points (baseline, 3 months, and 6 months); one group received the MBNR between time points 1 and 2, while a second group received it between time points 2 and 3. We found that both general EF and set shifting improved after the intervention, and this effect was maintained long term. Morphometric analyses revealed therapy-induced gray matter volume changes most consistently in the right inferior frontal gyrus, changes that correlated with better outcomes in set shifting. Finally, we found changes in the between- and within-network functional connectivity of large-scale resting-state networks after MBNR, which also correlated with measures of EF. Taken together, the data provide evidence for concluding that MBNR improves EF in TBI; also, the data show that morphometric and resting-state functional connectivity are sensitive markers with which to monitor the neuroplasticity induced by the MBNR intervention.

P211. Long-Term Effects of Maternal Stress and Depression on Within-Network Functional Connectivity in Young Adult Offspring

Maternal stress and depression during pregnancy and early postnatal period have been associated with depressive symptoms and altered brain structure in young adult offspring, but their impact on functional connectivity (FC) is less well-understood. Here, we set out to identify multivariate relationships between FC within multiple cortical networks and maternal adverstiy (stress and depression) assessed at multiple timepoints.