Hub Of Default Mode Network Research Articles

Structural-functional connectomics in major depressive disorder following aiTBS treatment

Major depressive disorder (MDD) has been associated with changes in the structural (SC) and functional connectivity (FC) of the brain. This study investigated the effects of accelerated intermittent theta burst stimulation (aiTBS) on SC-FC coupling and graph theory measures, focusing on the association between baseline SC-FC coupling of the dorsolateral prefrontal cortex (dlPFC) and clinical improvement. In a randomized, sham-controlled, quadruple-blind, crossover study, aiTBS was delivered to the left dlPFC of depressed patients with MDD, and diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rsfMRI) data were acquired. In 77 MDD patients, significantly increased whole-brain SC-FC coupling was observed, primarily driven by default mode network (DMN) SC-FC coupling, along with increased somatomotor network FC, and decreased FC between the DMN hubs and limbic regions after active aiTBS. Furthermore, significant increases were observed in structural global and local efficiency measures that were not specific to the stimulation condition (active/sham aiTBS). However, these changes did not significantly correlate with clinical improvement. Notably, baseline SC-FC coupling of the left dlPFC was a significant predictor of clinical improvement. Our findings highlight the potential of left dlPFC SC-FC coupling as a predictor of aiTBS treatment outcomes, as well as the effect of aiTBS in enhancing SC-FC coupling.

The interplay between insomnia symptoms and Alzheimer's disease across three main brain networks.

Insomnia symptoms are prevalent along the trajectory of Alzheimer's disease (AD), but the neurobiological underpinning of their interaction is poorly understood. Here, we assessed structural and functional brain measures within and between the default mode network (DMN), salience network, and central executive network (CEN). We selected 320 participants from the ADNI database and divided them by their diagnosis: cognitively normal (CN), Mild Cognitive Impairment (MCI), and AD, with and without self-reported insomnia symptoms. We measured the gray matter volume (GMV), structural covariance (SC), degrees centrality (DC), and functional connectivity (FC), testing the effect and interaction of insomnia symptoms and diagnosis on each index. Subsequently, we performed a within-group linear regression across each network and ROI. Finally, we correlated observed abnormalities with changes in cognitive and affective scores. Insomnia symptoms were associated with FC alterations across all groups. The AD group also demonstrated an interaction between insomnia and diagnosis. Within-group analyses revealed that in CN and MCI, insomnia symptoms were characterized by within-network hyperconnectivity, while in AD, within- and between-network hypoconnectivity was ubiquitous. SC and GMV alterations were nonsignificant in the presence of insomnia symptoms, and DC indices only showed network-level alterations in the CEN of AD individuals. Abnormal FC within and between DMN and CEN hubs was additionally associated with reduced cognitive function across all groups, and increased depressive symptoms in AD. We conclude that patients with clinical AD present with a unique pattern of insomnia-related functional alterations, highlighting the profound interaction between both conditions.

Posterior cingulate and medial prefrontal excitation-inhibition balance in euthymic bipolar disorder.

Persistent cognitive deficits and functional impairments are associated with bipolar disorder (BD), even during the euthymic phase. The dysfunction of default mode network (DMN) is critical for self-referential and emotional mental processes and is implicated in BD. The current study aims to explore the balance of excitatory and inhibitory neurotransmitters, i.e. glutamate and γ-aminobutyric acid (GABA), in hubs of the DMN during the euthymic patients with BD (euBD). Thirty-four euBD and 55 healthy controls (HC) were recruited to the study. Using proton magnetic resonance spectroscopy (1H-MRS), glutamate (with PRESS sequence) and GABA levels (with MEGAPRESS sequence) were measured in the medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and the posterior cingulate gyrus (PCC). Measured concentrations of excitatory glutamate/glutamine (Glx) and inhibitory GABA were used to calculate the excitatory/inhibitory (E/I) ratio. Executive and attentional functions were respectively assessed using the Wisconsin card-sorting test and continuous performance test. euBD performed worse on attentional function than controls (p = 0.001). Compared to controls, euBD had higher E/I ratios in the PCC (p = 0.023), mainly driven by a higher Glx level in the PCC of euBD (p = 0.002). Only in the BD group, a marginally significant negative association between the mPFC E/I ratio (Glx/GABA) and executive function was observed (p = 0.068). Disturbed E/I balance, particularly elevated Glx/GABA ratio in PCC is observed in euBD. The E/I balance in hubs of DMN may serve as potential biomarkers for euBD, which may also contribute to their poorer executive function.

Individual differences in the neural representation of cooperation and competition

Much evidence links the Big Five’s agreeableness to a propensity for cooperation and aggressiveness to a propensity for competition. However, the neural basis for these associations is unknown. In this functional magnetic resonance imaging study, using multivariate pattern analysis of data recorded during a computer game in which participants were required to construct target patterns either in cooperation or in competition with another person, we sought to determine how individual differences in neural representations of cooperative and competitive behavior relate to individual differences in agreeableness and aggressiveness. During cooperation, agreeableness was positively correlated with the consistency of spatial patterns of neural activation in the left temporoparietal junction (TPJ) and showed positive correlations with inter-subject similarity in the dynamics of neural responses in the posterior default mode network hub and areas involved in the regulation of attention, movement planning, and visual perception. During competition, aggressiveness was positively correlated with the consistency of spatial patterns in the left and right TPJ and showed positive correlations with neural dynamics in visual processing and movement regulation areas. These results are consistent with the assumption that agreeable individuals are more involved in cooperative interactions with others, whereas aggression-prone individuals are more involved in competitive interactions.

Default mode network aberrance in subjects of alcohol and opioid use disorders during working memory task: An exploratory EEG microstates study.

Aberrance in switching from default mode network (DMN) to fronto-parietal network (FPN) is proposed to underlie working memory deficits in subjects with substance use disorders, which can be studied using neuro-imaging techniques during cognitive tasks. The current study used EEG to investigate pre-stimulus microstates during the performance of Sternberg's working memory task in subjects with substance use disorders. 128-channel EEG was acquired and processed in ten age and gender-matched subjects, each with alcohol use disorder, opioid use disorder, and controls while they performed Sternberg's task. Behavioral parameters, pre-stimulus EEG microstate, and underlying sources were analyzed and compared between subjects with substance use disorders and controls. Both alcohol and opioid use disorder subjects had significantly lower accuracy (P < 0.01), while reaction times were significantly higher only in subjects of alcohol use disorder compared to controls (P < 0.01) and opioid use disorder (P < 0.01), reflecting working memory deficits of varying degrees in subjects with substance use disorders. Pre-stimulus EEG microstate revealed four topographic Maps 1-4: subjects of alcohol and opioid use disorder showing significantly lower mean duration of Map 3 (visual processing) and Map 2 (saliency and DMN switching), respectively, compared to controls (P < 0.05). Reduced mean durations in Map 3 and 2 in subjects of alcohol and opioid use disorder can underlie their poorer performance in Sternberg's task. Furthermore, cortical sources revealed higher activity in both groups of substance use disorders in the parahippocampal gyrus- a hub of DMN; superior and middle temporal gyri associated with impulsivity; and insula that maintains balance between executive reflective system and impulsive system. EEG microstates can be used to envisage neural underpinnings implicated for working memory deficits in subjects of alcohol and opioid use disorders, reflected by aberrant switching between neural networks and information processing mechanisms.

Concussion-Related Disruptions to Hub Connectivity in the Default Mode Network Are Related to Symptoms and Cognition.

Concussions present with a myriad of symptomatic and cognitive concerns; however, the relationship between these functional disruptions and the underlying changes in the brain are not yet well understood. Hubs, or brain regions that are connected to many different functional networks, may be specifically disrupted after concussion. Given the implications in concussion research, we quantified hub disruption within the default mode network (DMN) and between the DMN and other brain networks. We collected resting-state functional magnetic resonance imaging data from collegiate student-athletes (n = 44) at three time points: baseline (before beginning their athletic season), acute post-injury (approximately 48h after a diagnosed concussion), and recovery (after starting return-to-play progression, but before returning to contact). We used self-reported symptoms and computerized cognitive assessments collected across similar time points to link these functional connectivity changes to clinical outcomes. Concussion resulted in increased connectivity between regions within the DMN compared with baseline and recovery, and this post-injury connectivity was more positively related to symptoms and more negatively related to visual memory performance compared with baseline and recovery. Further, concussion led to decreased connectivity between DMN hubs and visual network non-hubs relative to baseline and recovery, and this post-injury connectivity was more negatively related to somatic symptoms and more positively related to visual memory performance compared with baseline and recovery. Relationships between functional connectivity, symptoms, and cognition were not significantly different at baseline versus recovery. These results highlight a unique relationship between self-reported symptoms, visual memory performance, and acute functional connectivity changes involving DMN hubs after concussion in athletes. This may provide evidence for a disrupted balance of within- and between-network communication highlighting possible network inefficiencies after concussion. These results aid in our understanding of the pathophysiological disruptions after concussion and inform our understanding of the associations between disruptions in brain connectivity and specific clinical presentations acutely post-injury.

Meditation attenuates default-mode activity: A pilot study using ultra-high field 7 Tesla MRI

ObjectivesMapping the neurobiology of meditation has been bolstered by functional MRI (fMRI) research, with advancements in ultra-high field 7 Tesla fMRI further enhancing signal quality and neuroanatomical resolution. Here, we utilize 7 Tesla fMRI to examine the neural substrates of meditation and replicate existing widespread findings, after accounting for relevant physiological confounds. MethodsIn this feasibility study, we scanned 10 beginner meditators (N = 10) while they either attended to breathing (focused attention meditation) or engaged in restful thinking (non-focused rest). We also measured and adjusted the fMRI signal for key physiological differences between meditation and rest. Finally, we explored changes in state mindfulness, state anxiety and focused attention attributes for up to 2 weeks following the single fMRI meditation session. ResultsGroup-level task fMRI analyses revealed significant reductions in activity during meditation relative to rest in default-mode network hubs, i.e., antero-medial prefrontal and posterior cingulate cortices, precuneus, as well as visual and thalamic regions. These findings survived stringent statistical corrections for fluctuations in physiological responses which demonstrated significant differences (p < 0.05/n, Bonferroni controlled) between meditation and rest. Compared to baseline, State Mindfulness Scale (SMS) scores were significantly elevated (F(3,9) = 8.16, p < 0.05/n, Bonferroni controlled) following the fMRI meditation session, and were closely maintained at 2-week follow up. ConclusionsThis pilot study establishes the feasibility and utility of investigating focused attention meditation using ultra-high field (7 Tesla) fMRI, by supporting widespread evidence that focused attention meditation attenuates default-mode activity responsible for self-referential processing. Future functional neuroimaging studies of meditation should control for physiological confounds and include behavioural assessments.

Vesicular Glutamate Transporter Changes in the Cortical Default Mode Network During the Clinical and Pathological Progression of Alzheimer's Disease.

Altered glutamatergic neurotransmission may contribute to impaired default mode network (DMN) function in Alzheimer's disease (AD). Among the DMN hub regions, frontal cortex (FC) was suggested to undergo a glutamatergic plasticity response in prodromal AD, while the status of glutamatergic synapses in the precuneus (PreC) during clinical-neuropathological AD progression is not known. To quantify vesicular glutamate transporter VGluT1- and VGluT2-containing synaptic terminals in PreC and FC across clinical stages of AD. Unbiased sampling and quantitative confocal immunofluorescence of cortical VGluT1- and VGluT2-immunoreactive profiles and spinophilin-labeled dendritic spines were performed in cases with no cognitive impairment (NCI), mild cognitive impairment (MCI), mild-moderate AD (mAD), or moderate-severe AD (sAD). In both regions, loss of VGluT1-positive profile density was seen in sAD compared to NCI, MCI, and mAD. VGluT1-positive profile intensity in PreC did not differ across groups, while in FC it was greater in MCI, mAD, and sAD compared to NCI. VGluT2 measures were stable in PreC while FC had greater VGluT2-positive profile density in MCI compared to sAD, but not NCI or mAD. Spinophilin measures in PreC were lower in mAD and sAD compared to NCI, while in FC they were stable across groups. Lower VGluT1 and spinophilin measures in PreC, but not FC, correlated with greater neuropathology. Frank loss of VGluT1 in advanced AD relative to NCI occurs in both DMN regions. In FC, an upregulation of VGluT1 protein content in remaining glutamatergic terminals may contribute to this region's plasticity response in AD.

Altered brain connectivity in Long Covid during cognitive exertion: a pilot study.

Debilitating Long-Covid symptoms occur frequently after SARS-COVID-19 infection. Functional MRI was acquired in 10 Long Covid (LCov) and 13 healthy controls (HC) with a 7 Tesla scanner during a cognitive (Stroop color-word) task. BOLD time series were computed for 7 salience and 4 default-mode network hubs, 2 hippocampus and 7 brainstem regions (ROIs). Connectivity was characterized by the correlation coefficient between each pair of ROI BOLD time series. We tested for HC versus LCov differences in connectivity between each pair of the 20 regions (ROI-to-ROI) and between each ROI and the rest of the brain (ROI-to-voxel). For LCov, we also performed regressions of ROI-to-ROI connectivity with clinical scores. Two ROI-to-ROI connectivities differed between HC and LCov. Both involved the brainstem rostral medulla, one connection to the midbrain, another to a DM network hub. Both were stronger in LCov than HC. ROI-to-voxel analysis detected multiple other regions where LCov connectivity differed from HC located in all major lobes. Most, but not all connections, were weaker in LCov than HC. LCov, but not HC connectivity, was correlated with clinical scores for disability and autonomic function and involved brainstem ROI. Multiple connectivity differences and clinical correlations involved brainstem ROIs. Stronger connectivity in LCov between the medulla and midbrain may reflect a compensatory response. This brainstem circuit regulates cortical arousal, autonomic function and the sleep-wake cycle. In contrast, this circuit exhibited weaker connectivity in ME/CFS. LCov connectivity regressions with disability and autonomic scores were consistent with altered brainstem connectivity in LCov.

Individual differences in delay discounting are associated with dorsal prefrontal cortex connectivity in children, adolescents, and adults

Delay discounting is a measure of impulsive choice relevant in adolescence as it predicts many real-life outcomes, including obesity and academic achievement. However, resting-state functional networks underlying individual differences in delay discounting during youth remain incompletely described. Here we investigate the association between multivariate patterns of functional connectivity and individual differences in impulsive choice in a large sample of children, adolescents, and adults. A total of 293 participants (9–23 years) completed a delay discounting task and underwent 3T resting-state fMRI. A connectome-wide analysis using multivariate distance-based matrix regression was used to examine whole-brain relationships between delay discounting and functional connectivity. These analyses revealed that individual differences in delay discounting were associated with patterns of connectivity emanating from the left dorsal prefrontal cortex, a default mode network hub. Greater delay discounting was associated with greater functional connectivity between the dorsal prefrontal cortex and other default mode network regions, but reduced connectivity with regions in the dorsal and ventral attention networks. These results suggest delay discounting in children, adolescents, and adults is associated with individual differences in relationships both within the default mode network and between the default mode and networks involved in attentional and cognitive control.

Refugee visa insecurity disrupts the brain’s default mode network

ABSTRACT Background: Research has largely focused on the psychological consequences of refugee trauma exposure, but refugees living with visa insecurity face an uncertain future that also adversely affects psychological functioning and self-determination. Objective: This study aimed to examine how refugee visa insecurity affects the functional brain. Method: We measured resting state brain activity via fMRI in 47 refugees with insecure visas (i.e. temporary visa status) and 52 refugees with secure visas (i.e. permanent visa status) residing in Australia, matched on key demographic, trauma exposure and psychopathology. Data analysis comprised independent components analysis to identify active networks and dynamic functional causal modelling tested visa security group differences in network connectivity. Results: We found that visa insecurity specifically affected sub-systems within the default mode network (DMN) – an intrinsic network subserving self-referential processes and mental simulations about the future. The insecure visa group showed less spectral power in the low frequency band in the anterior ventromedial DMN, and reduced activity in the posterior frontal DMN, compared to the secure visa group. Using functional dynamic causal modelling, we observed positive coupling between the anterior and posterior midline DMN hubs in the secure visa group, while the insecure visa group displayed negative coupling that correlated with self-reported fear of future deportation. Conclusions: Living with visa-related uncertainty appears to undermine synchrony between anterior-posterior midline components of the DMN responsible for governing the construction of the self and making mental representations of the future. This could represent a neural signature of refugee visa insecurity, which is marked by a perception of living in limbo and a truncated sense of the future.

451 Posterior Cingulate Theta Power as a Novel Biomarker of Mood

INTRODUCTION: One third of patients with major depressive disorder (MDD) are refractory to standard therapies. Progress in therapeutic neuromodulation for depression has been challenging because of the widespread, network basis of mood and lack of neurophysiologic biomarkers. Neuroimaging studies of depression demonstrate increased connectivity within the default mode network (DMN), which subserves internal processes such as self-reflection, mind wandering, and memory. Invasive electrophysiology in the resting state has demonstrated that DMN connectivity corresponds to correlations in theta-band power. DMN activity is anti-correlated with the dorsal attention network (DAN) which, in contrast, subserves externally oriented cognition (i.e., top-down attention), and demonstrates alpha-specific resting-state correlations. METHODS: We used hourly, self-reported measures of mood and video facial affect recognition to estimate mood valence in six epilepsy patients undergoing invasive stereotactic electroencephalography monitoring. We analyzed power spectra and functional connectivity (band-limited power correlations) in epochs corresponding to mood estimates. Patients without substantial inpatient mood variability (n=3) were excluded. RESULTS: Depressed mood was correlated with increased theta power. This was most significant in electrodes within posterior cingulate cortex (DMN region; r = -0.58; p = 0.0007). Conversely, alpha power was increased during elevated mood, most significantly in the intraparietal sulcus (DAN region; r = 0.55, p = 0.0013). Theta connectivity was correlated with depressed mood (r = -0.53, p = 0.003) whereas alpha connectivity was correlated with elevated mood (r = 0.56, p = 0.002). CONCLUSIONS: Our results recapitulate the frequency specificity of resting-state physiology and encourage a network-based perspective of depression neurophysiology. Theta and alpha power within DMN and DAN networks, respectively, represent important biomarkers of mood and may guide neuromodulatory therapies. Posterior cingulate/precuneus cortex is a major DMN hub and should be sampled in future studies of neural correlates of mood.

Disrupted structural brain networks across psychiatric disorders determined using multivariate graph analyses

IntroductionIdentifying the specific brain pattern characterizing psychiatric disorders could lead us to precise diagnostic process, better treatment plan and outcome prediction. Structural covariance is a graph-analysis method with which disruptions in large scale brain network organization can be observed. More studies, employing this method in psychiatry, are still needed.ObjectivesThe current study aims to investigate how the main psychiatric disorders – schizophrenia, major depressive disorder, bipolar disorder, affect brain circuitry by means of multivariate graph theory, more specifically – structural covariance. We hypothesized that specific abnormalities in the brain circuits would be found in separate diagnostic entities.Methods164 subjects were included with schizophrenia-SCH (n=17), bipolar disorder-BD(n=25), major depressive disorder–MDD(n=68) and a healthy control group-HC(n=54). Each participant provided a written informed consent and the study protocol was approved by the University’s Ethics Committee. High resolution structural MRI was acquired, and preprocessing was performed using SPM 12 toolbox. The structural covariance method was applied consisting of calculation of the correlation across subjects between the different pairs of regions by using the gray matter average volume. We used the threshold statistic to binarize the covariance matrix and transform it into an adjacency matrix. This allows us to compare psychiatric disorders at a network level by calculating measures such as authorities, hubs and outdegree.Results61 statistically significant regions were found for the whole sample. The matrices of the four groups were compared according to their ‘authorities’ ,‘hubs’ and ‘outdegree’ as first, second and third ranking variables, respectively. In the group comparison between HC and BD patients the top five significant regions were Planum temporale (PT), Putamen, Precuneus (PreCu), Calcarine cortex (Calc_cor) and Postcentral gyrus medial segment (PostCGms). The MDD group demonstrated the following regions with most significant difference including Precentral gyrus (PreCG), Entorhinal area (EntA), Amygdala (Amy), Anterior cingulate gyrus (ACC), Anterior insula (AI). While SCH grop was charachterized by ACC, PreCG – medial segment, PostCGms, anterior orbital gyrus, and frontal pole.ConclusionsThe results of our study demonstrated that schizophrenia and mood disorders have specific disturbances in brain network structural organization, affecting hubs of default mode network, salience network, motor, sensory and visual cortex, as well as limbic system. These alterations might elucidate the pathophysiological mechanisms of common symptoms of the disorders under investigation including perceptual, affective and cognitive disturbances.Disclosure of InterestNone Declared

Measures of Brain Connectivity and Cognition by Sex in US Children

The neurobiological underpinnings underlying sex differences in cognition during adolescence are largely unknown. To examine sex differences in brain circuitry and their association with cognitive performance in US children. This cross-sectional study analyzed behavioral and imaging data from 9- to 11-year-old children from the Adolescent Brain Cognitive Development (ABCD) study between August 2017 and November 2018. The ABCD study is an open-science, multisite study following up more than 11 800 youths into early adulthood for 10 years with annual laboratory-based assessments and biennial magnetic resonance imaging (MRI). The selection of ABCD study children for the current analysis was based on the availability of functional and structural MRI data sets in ABCD Brain Imaging Data Structure Community Collection format. Five hundred and sixty participants who had excessive level of head motion (>50% of time points with framewise displacement >0.5 mm) during resting-state functional MRI were excluded from the analyses. Data were analyzed between January and August 2022. The main outcomes were the sex differences in (A) global functional connectivity density at rest and (B) mean water diffusivity (MD) and (C) the correlation of these metrics with total cognitive scores. A total of 8961 children (4604 boys and 4357 girls; mean [SD] age, 9.92 [0.62] years) were included in this analysis. Girls had higher functional connectivity density in default mode network hubs than boys, predominantly in the posterior cingulate cortex (Cohen d = -0.36), and lower MD and transverse diffusivity, predominantly in the superior corticostriatal white matter bundle (Cohen d = 0.3). Age-corrected fluid and total composite scores were higher for girls than for boys (Cohen d = -0.08 [fluid] and -0.04 [total]; P = 2.7 × 10-5). Although total mean (SD) brain volume (1260 [104] mL in boys and 1160 [95] mL in girls; t = 50; Cohen d = 1.0; df = 8738) and the proportion of white matter (d = 0.4) were larger for boys than for girls, the proportion of gray matter was larger for girls than for boys (d = -0.3; P = 2.2 × 10-16). The findings of this cross-sectional study on sex differences in brain connectivity and cognition are relevant to the future creation of brain developmental trajectory charts to monitor for deviations associated with impairments in cognition or behavior, including those due to psychiatric or neurological disorders. They could also serve as a framework for studies investigating the differential contribution of biological vs social or cultural factors in the neurodevelopmental trajectories of girls and boys.

The autism spectrum among transgender youth: default mode functional connectivity.

The common intersection of autism and transgender identities has been described in clinical and community contexts. This study investigates autism-related neurophenotypes among transgender youth. Forty-five transgender youth, evenly balanced across non-autistic, slightly subclinically autistic, and full-criteria autistic subgroupings, completed resting-state functional magnetic resonance imaging to examine functional connectivity. Results confirmed hypothesized default mode network (DMN) hub hyperconnectivity with visual and motor networks in autism, partially replicating previous studies comparing cisgender autistic and non-autistic adolescents. The slightly subclinically autistic group differed from both non-autistic and full-criteria autistic groups in DMN hub connectivity to ventral attention and sensorimotor networks, falling between non-autistic and full-criteria autistic groups. Autism traits showed a similar pattern to autism-related group analytics, and also related to hyperconnectivity between DMN hub and dorsal attention network. Internalizing, gender dysphoria, and gender minority-related stigma did not show connectivity differences. Connectivity differences within DMN followed previously reported patterns by designated sex at birth (i.e. female birth designation showing greater within-DMN connectivity). Overall, findings suggest behavioral diagnostics and autism traits in transgender youth correspond to observable differences in DMN hub connectivity. Further, this study reveals novel neurophenotypic characteristics associated with slightly subthreshold autism, highlighting the importance of research attention to this group.

Connectivity Between Salience and Default Mode Networks and Subcortical Nodes Distinguishes Between Two Classes of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease with unknown pathophysiology. Functional magnetic resonance imaging (fMRI) studies in ME/CFS have reported disparate connectivities for the brain salience (SA) network and default mode network (DMN). Materials and Methods: In this study, we acquired resting-state and task fMRI with an advanced scanner for improved subject numbers: 24 healthy controls (HC) and 42 ME/CFS patients, 18 meeting the International Consensus Criteria (ICC) and 24 meeting the Fukuda criteria. We evaluated mean functional connectivity between the SA network and DMN hubs and subcortical regions known to be involved in ME/CFS. We tested the hypothesis that ME/CFS connectivity differed from HC and the ICC and Fukuda classes are distinguished by different connectivities with HC for different pairs of SA network, DMN, or subcortical hubs. Results: During resting-state fMRI, only two connections differed from HC, both for Fukuda ME/CFS and both with an SA network hub. During task fMRI, 10 ME/CFS connections differed from HC, 5 for ICC, and 5 for Fukuda. None was common to both classes. Eight of the 10 different connections involved an SA network hub, six of the 10 were weaker in ME/CFS, and 4 were stronger. SA network connections to the hippocampus and brainstem reticular activation system (RAS) differed from and were stronger than HC. Conclusions: The SA network mediates the relative activity of the DMN and executive networks and an imbalance will have functional consequences. The RAS and hippocampus modulate cortical activation. Different regulatory connections are consistent with the impaired cognitive performance and sleep-wake cycle of ME/CFS. Different neuropathologies are involved in ICC and Fukuda classes. Impact statement Criteria for the diagnosis of the debilitating myalgic encephalitis/chronic fatigue syndrome (ME/CFS) condition have evolved over two decades. Physicians are now instructed that the recent, more stringent (ICC) questionnaire criteria define a disease that is distinct from those remaining subjects defined by the previous Fukuda criteria. This work reports the remarkable finding that functional magnetic resonance imaging connectivity can differentiate between these two classes of ME/CFS. This is the first objective medical evidence that the questionnaire-based diagnosis does indeed differentiate between two different disease states. This facilitates a clearer understanding of ME/CFS and can better direct research and therapy development.

Topological reorganization of brain network might contribute to the resilience of cognitive functioning in mildly disabled relapsing remitting multiple sclerosis.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease which leads to impairment in several functional systems including cognition. Alteration of brain networks is linked to disability and its progression. However, results are mostly cross-sectional and yet contradictory as putative adaptive and maladaptive mechanisms were found. Here, we aimed to explore longitudinal reorganization of brain networks over 2-years by combining diffusion tensor imaging (DTI), resting-state functional MRI (fMRI), magnetoencephalography (MEG), and a comprehensive neuropsychological-battery. In 37 relapsing-remitting MS (RRMS) and 39 healthy-controls, cognition remained stable over-time. We reconstructed network models based on the three modalities and analyzed connectivity in relation to the hierarchical topology and functional subnetworks. Network models were compared across modalities and in their association with cognition using linear-mixed-effect-regression models. Loss of hub connectivity and global reduction was observed on a structural level over-years (p< .010), which was similar for functional MEG-networks but not for fMRI-networks. Structural hub connectivity increased in controls (p= .044), suggesting a physiological mechanism of healthy aging. Despite a general loss in structural connectivity in RRMS, hub connectivity was preserved (p= .002) over-time in default-mode-network (DMN). MEG-networks were similar to DTI and weakly correlated with fMRI in MS (p< .050). Lower structural (β between .23-.33) and both lower (β between .40-.59) and higher functional connectivity (β= -.54) in DMN was associated with poorer performance in attention and memory in RRMS (p< .001). MEG-networks involved no association with cognition. Here, cognitive stability despite ongoing neurodegeneration might indicate a resilience mechanism of DMN hubs mimicking a physiological reorganization observed in healthy aging.

Serum neurofilament light chain is associated with disturbed limbic-based functional connectivity in patients with anti-NMDAR encephalitis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis shows a predilection for affecting the limbic system, but structural MRI in most patients is usually unremarkable. However, the functional connectivity reorganization of limbic nodes remains unknown. Serum neurofilament light chains (sNfL) are clinically linked with the disease severity and neurological disability of anti-NMDAR encephalitis. However, the relationship between sNfL and limbic-based functional architecture has not been explored. We consecutively recruited 20 convalescent patients with anti-NMDAR encephalitis and 24 healthy controls from March 2018 to March 2021. Resting-state functional MRI metrics, including fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and atlas-based seed functional connectivity, were analyzed to investigate regional activities and functional connectivity alterations. Correlation analysis among functional connectivity, sNfL, Mini-Mental State Examination (MMSE), and Montreal cognitive assessment outcomes were explored in patients. Compared with those of healthy controls, the fALFF and ReHo were consistently increased in regions of the posterior default mode network (DMN) hub, mainly the bilateral supramarginal gyrus and precuneus, in patients with anti-NMDAR encephalitis (FWE-corrected p< 0.05). Patients demonstrated disturbed functional organization characterized by reduced connectivity of the posterior DMN hub with the sensorimotor cortex and hypoconnectivity of the parahippocampal gyrus (PHG) with the right fusiform gyrus but extensively enhanced thalamocortical connectivity (FWE-corrected p< 0.05). Furthermore, convalescent sNfL showed a positive correlation with enhanced thalamocortical connectivity (r= 0.4659, p= 0.0384). Onset sNfL with an independent linear correlation to convalescent MMSE performance (B coefficient, -0.013, 95% CI, -0.025 ~ -0.002, p= 0.0260) was positively correlated with intra-DMN connectivity (r= 0.8969, p< 0.0001) and limbic-sensory connectivity (r= 0.4866, p= 0.0346 for hippocampus seed and r= 0.5218, p= 0.0220 for PHG seed). Patients with anti-NMDAR encephalitis demonstrated disturbed functional organization with substantial thalamocortical hyperconnectivity, that was positively correlated with convalescent sNfL. Onset sNfL showed a positive correlation with intra-DMN connectivity and limbic-sensory connectivity.

Shared and distinct structure-function substrates of heterogenous distractor suppression ability between high and low working memory capacity individuals

Salient stimuli can capture attention in a bottom-up manner; however, this attentional capture can be suppressed in a top-down manner. It has been shown that individuals with high working memory capacity (WMC) can suppress salient‑but-irrelevant distractors better than those with low WMC; however, neural substrates underlying this difference remain unclear. To examine this, participants with high or low WMC (high-/low-WMC, n = 44/44) performed a visual search task wherein a color singleton item served as a salient distractor, and underwent structural and resting-state functional magnetic resonance imaging scans. Behaviorally, the color singleton distractor generally reduced the reaction time (RT). This RT benefit (ΔRT) was higher in the high-WMC group relative to the low-WMC group, indicating the superior distractor suppression ability of the high-WMC group. Moreover, leveraging voxel-based morphometry analysis, gray matter morphology (volume and deformation) in the ventral attention network (VAN) was found to show the same, positive associations with ΔRT in both WMC groups. However, correlations of the opposite sign were found between ΔRT and gray matter morphology in the frontoparietal (FPN)/default mode network (DMN) in the two WMC groups. Furthermore, resting-state functional connectivity analysis centering on regions with a structural-behavioral relationship found that connections between the left orbital and right superior frontal gyrus (hubs of DMN and VAN, respectively) was correlated with ΔRT in the high-WMC group (but not in the low-WMC group). Collectively, our work present shared and distinct neuroanatomical substrates of distractor suppression in high- and low-WMC individuals. Furthermore, intrinsic connectivity of the brain network hubs in high-WMC individuals may account for their superior ability in suppressing salient distractors.

A-04 Acute Sports-Related Concussion Associations Between Cognitive Symptoms, Memory Performance, and Default Mode Network Hub Connectivity

Abstract Purpose: Disruptions in cognitive performance are commonly reported after a sports-related concussion (SRC) and may be related to brain network changes, particularly within the default mode network (DMN). Since well-connected brain regions across networks (hubs) play an important role in network organization, we hypothesize that DMN hubs will be disrupted after a SRC and associated with cognitive symptoms and cognitive performance. Methods: We collected resting-state fMRI, symptoms, and cognitive performance data from 44 student-athletes at baseline, after a SRC, and at recovery. Participation coefficient defined hubs for each athlete. We compared changes in functional connectivity between hubs and non-hubs within the DMN and between DMN hubs and non-hubs in the remaining networks. We used linear regression to examine the relationship between functional connectivity, cognitive symptoms, and cognitive performance while controlling for concussion history. Results: Functional connectivity between hubs and non-hubs within the DMN increased from baseline to post-injury and decreased from post-injury to recovery, but not to baseline connectivity levels. Post-injury functional connectivity was related to increased cognitive symptoms and decreased visual memory performance. Functional connectivity decreased between hubs in the DMN and non-hubs in the cingulo-opercular, salience, somatomotor, and visual networks from baseline to post-injury. Cognitive symptoms and visual memory performance were related to functional connectivity between DMN hubs and visual network non-hubs. Conclusions: Self-reported cognitive symptoms and cognitive performance were associated with changes in DMN hub connectivity. This relationship may suggest a decrease in efficiency between brain networks after a SRC and may provide insight into post-injury compensation during task performance.