Resting-state Functional Connectivity Patterns Research Articles

Brain functional connectivity patterns associated with symptoms of vestibular migraine.

Several functional magnetic resonance imaging (fMRI) investigations of patients with vestibular migraine (VM) have revealed abnormal functionality in different networks, indicating that VM is related to alterations in brain function. We sought to investigate the resting-state functional connectivity (FC) patterns during the interictal period in VM by combining data-driven voxel-wise degree centrality (DC) calculations and seed-based FC analyses, and thereby determine the associations between cerebral function and clinical symptoms. Thirty-eight patients with VM and 33 matched normal controls were recruited. DC was calculated and compared between the groups, and the FC of locations showing DC alterations was further tested using a seed-based technique. The participants' clinical indicators were correlated with the DC and FC values of the brain areas. In contrast to the control group, the VM group showed considerably lower DC values in the bilateral medial prefrontal cortex (mPFC) and significantly higher DC values in the right occipital lobe. In the seed-based FC analyses, patients with VM demonstrated fewer connections of the bilateral mPFC with the bilateral posterior cingulate cortex, right parahippocampus, right cerebellar posterior lobe, bilateral cuneus, and left precuneus. In addition, clinical data from patients, such as pain intensity, episode frequency, and the Dizziness Handicap Inventory score, were negatively related to these FC and DC impairments. Our findings showed changes in the default mode network and visual cortex in patients with VM, providing further insights into the complexity of the mechanisms underlying VM.

Associations Between Lifetime Musical Activity and Resting‐State Functional Connectivity in Higher‐Order Brain Networks

AbstractBackgroundEngagement in complex leisure activities, such as playing a musical instrument, may help preserve cognitive and brain health in older age (e.g. Böttcher et al., 2022). In this study, we investigated the associations between leisure‐time musical activity and resting‐state functional connectivity (RSFC) in three higher‐order networks, the Default Mode. Fronto‐Parietal and Salience Networks, in older adults.MethodIn total, 130 cognitively unimpaired older (aged 60 years and older) participants of the DZNE ‐ DELCODE (Jessen et al., 2018) were assessed. Two groups matched for their reserve proxies were identified (with musical activity during life: n = 65 and controls: n = 65) based on self‐reported musical instrument playing during life, as measured by the Lifetime of Experiences Questionnaire. The two groups were compared in global and local (seed‐to‐voxel) RSFC patterns using pre‐specified seeds of the three brain networks. A mediation analysis explored the interrelations between lifetime musical activity, RSFC, and cognitive composites (Wolfsgruber et al., 2020).ResultOlder participants with musical activity showed higher local RSFC between the medial prefrontal cortex (Default Mode Network seed) and temporal regions, namely the bilateral temporal poles as well as the right inferior and middle temporal gyrus, compared to controls (see Figure 1). There were no group differences in global RSFC of the three networks and no mediation effects of musical activity‐related RSFC on global and domain‐specific cognition.ConclusionWe show that self‐reported lifetime musical activity relates to higher RSFC between frontal and temporal core regions of the Default Mode Network in older adults. The finding implies that playing a musical instrument during life may help preserve neural functioning in a key network that is vulnerable to aging and AD.

Uncovering individual variations in bystander intervention of injustice through intrinsic brain connectivity patterns

When confronted with injustice, individuals often intervene as third parties to restore justice by either punishing the perpetrator or helping the victim, even at their own expense. However, little is known about how individual differences in third-party intervention propensity are related to inter-individual variability in intrinsic brain connectivity patterns and how these associations vary between help and punishment intervention. To address these questions, we employed a novel behavioral paradigm in combination with resting-state fMRI and inter-subject representational similarity analysis (IS-RSA). Participants acted as third-party bystanders and needed to decide whether to maintain the status quo or intervene by either helping the disadvantaged recipient (Help condition) or punishing the proposer (Punish condition) at a specific cost. Our analyses focused on three brain networks proposed in the third-party punishment (TPP) model: the salience (e.g., dorsal anterior cingulate cortex, dACC), central executive (e.g., dorsolateral prefrontal cortex, dlPFC), and default mode (e.g., dorsomedial prefrontal cortex, dmPFC; temporoparietal junction, TPJ) networks. IS-RSA showed that individual differences in resting-state functional connectivity (rs-FC) patterns within these networks were associated with the general third-party intervention propensity. Moreover, rs-FC patterns of the right dlPFC and right TPJ were more strongly associated with individual differences in the helping propensity rather than the punishment propensity, whereas the opposite pattern was observed for the dmPFC. Post-hoc predictive modeling confirmed the predictive power of rs-FC in these regions for intervention propensity across individuals. Collectively, these findings shed light on the shared and distinct roles of key regions in TPP brain networks at rest in accounting for individual variations in justice-restoring intervention behaviors.

Resting-state cortico-limbic functional connectivity pattern in panic disorder: Relationships with emotion regulation strategy use and symptom severity

Cognitive reappraisal is an effective emotion regulation strategy involving prefrontal cortex (PFC) control of the amygdala. Its aberrant functioning is closely associated with panic disorder (PD). However, the resting-state functional connectivity (rsFC) between the PFC, implicated in cognitive reappraisal, and the amygdala in PD has not been studied. Thus, this study aims to investigate the rsFC patterns and their association with cognitive reappraisal and PD. This study involved 51 participants, including 26 untreated patients with PD and 25 healthy controls (HC). We evaluated the habit of cognitive reappraisal assessment and the severity of PD using neuropsychological and clinical measures. Resting-state fMRI was utilized to evaluate the rsFC pattern between the PFC, engaged in cognitive reappraisal, and the amygdala. Mediation analysis was performed to explore the role of this rsFC in the relationship between cognitive reappraisal and PD severity. PD patients showed reduced rsFC between the PFC and the amygdala compared to HC. This weakened rsFC was associated with the severity of PD symptoms. Moreover, cognitive reappraisal was negatively correlated with PD severity, and mediation analysis indicated that the rsFC of the PFC-amygdala played a mediating role in this association. Abnormal PFC-amygdala rsFC may play a pivotal role in PD development and/or manifestation and mediate the association between cognitive reappraisal and PD severity, potentially serving as a clinical indicator for monitoring and intervention.

Disrupted executive cerebro-cerebellar functional connectivity in alcohol use disorder.

Alcohol use disorder (AUD) affects 283 million people worldwide and its prevalence is increasing. Despite the role of the cerebellum in executive control and its sensitivity to alcohol, few studies have assessed its involvement in AUD-relevant functional networks. The goal of this study is to compare resting-state functional connectivity (FC) patterns in abstinent adults with a history of AUD and controls (CTL). We hypothesized that group differences in cerebro-cerebellar FC would be present, particularly within the frontoparietal/executive control network (FPN). Twenty-eight participants completed a resting-state functional magnetic resonance imaging (rsfMRI) study. CTL participants had no history of AUD, comorbid psychological conditions, or recent heavy drinking and/or drug use. AUD participants had a history of AUD, with sobriety for at least 30 days prior to data collection. Multivariate pattern analysis, an agnostic, whole-brain approach, was used to identify regions with significant differences in FC between groups. Seed-based analyses were then conducted to determine the directionality and extent of these FC differences. Associations between FC strength and executive function were assessed using correlations with Wisconsin Card Sorting Test (WCST) performance. There were significant group differences in FC in nodes of the FPN, ventral attention network, and default mode network. Post hoc analyses predominantly identified FC differences within the cerebro-cerebellar FPN, with AUD showing significantly less FC within the FPN. In AUD, FC strength between FPN clusters identified in the multivariate pattern analysis (MVPA) analysis (Left Crus II, Right Frontal Cortex) was positively associated with performance on the WCST. Our results show less engagement of the FPN in individuals with AUD than in CTL. FC strength within this network was positively associated with performance on the WCST. These findings suggest that long-term heavy drinking alters cerebro-cerebellar FC, particularly within networks that are involved in executive function.

Dimensional subtyping of first-episode drug-naïve major depressive disorder: A multisite resting-state fMRI study

Major depressive disorder (MDD) is a heterogeneous syndrome, and understanding its neural mechanisms is crucial for the advancement of personalized medicine. However, conventional subtyping studies often categorize MDD patients into a single subgroup, neglecting the continuous interindividual variations. This implies a pressing need for a dimensional approach. 230 first-episode drug-naïve MDD patients and 395 healthy controls were obtained from 5 sites via the Rest-meta-MDD project. A Bayesian model was used to decompose the resting-state functional connectivity (RSFC) into multiple distinct RSFC patterns (refer to as “factors”), and each individual was allowed to express multiple factors to varying degrees (dimensional subtyping). The associations between demographic and clinical variables with the identified factors were calculated. We identified three latent factors with distinct but partially overlapping hypo- and hyper-RSFC patterns. Most participants co-expressed multiple latent factors. All factors shared abnormal RSFC involving the default mode network and frontoparietal network, but the directionality partially differed across factors. All factors were not significantly associated with demographic and clinical variables. These findings shed light on the interindividual variability in MDD and could form the basis for developing novel therapeutic approaches that capitalize on the heterogeneity of MDD.

Predicting executive functioning from brain networks: modality specificity and age effects.

Healthy aging is associated with structural and functional network changes in the brain, which have been linked to deterioration in executive functioning (EF), while their neural implementation at the individual level remains unclear. As the biomarker potential of individual resting-state functional connectivity (RSFC) patterns has been questioned, we investigated to what degree individual EF abilities can be predicted from the gray-matter volume (GMV), regional homogeneity, fractional amplitude of low-frequency fluctuations (fALFF), and RSFC within EF-related, perceptuo-motor, and whole-brain networks in young and old adults. We examined whether the differences in out-of-sample prediction accuracy were modality-specific and depended on age or task-demand levels. Both uni- and multivariate analysis frameworks revealed overall low prediction accuracies and moderate-to-weak brain-behavior associations (R2< 0.07, r< 0.28), further challenging the idea of finding meaningful markers for individual EF performance with the metrics used. Regional GMV, well linked to overall atrophy, carried the strongest information about individual EF differences in older adults, whereas fALFF, measuring functional variability, did so for younger adults. Our study calls for future research analyzing more global properties of the brain, different task-states and applying adaptive behavioral testing to result in sensitive predictors for young and older adults, respectively.

Investigating the heterogeneity within the somatosensory-motor network and its relationship with the attention and default systems.

The somatosensory-motor network (SMN) not only plays an important role in primary somatosensory and motor processing but is also central to many disorders. However, the SMN heterogeneity related to higher-order systems still remains unclear. Here, we investigated SMN heterogeneity from multiple perspectives. To characterize the SMN substructures in more detail, we used ultra-high-field functional MRI to delineate a finer-grained cortical parcellation containing 430 parcels that is more homogenous than the state-of-the-art parcellation. We personalized the new parcellation to account for individual differences and identified multiscale individual-specific brain structures. We found that the SMN subnetworks showed distinct resting-state functional connectivity (RSFC) patterns. The Hand subnetwork was central within the SMN and exhibited stronger RSFC with the attention systems than the other subnetworks, whereas the Tongue subnetwork exhibited stronger RSFC with the default systems. This two-fold differentiation was observed in the temporal ordering patterns within the SMN. Furthermore, we characterized how the distinct attention and default streams were carried forward into the functions of the SMN using dynamic causal modeling and identified two behavioral domains associated with this SMN fractionation using meta-analytic tools. Overall, our findings provided important insights into the heterogeneous SMN organization at the system level and suggested that the Hand subnetwork may be preferentially involved in exogenous processes, whereas the Tongue subnetwork may be more important in endogenous processes.

The effect of erenumab on brain network function in episodic migraine patients: a randomized, placebo-controlled clinical trial (RESET BRAIN)

BackgroundWe aimed to explore whether erenumab, a monoclonal antibody targeting the calcitonin gene-related peptide receptor, could exert a central effect on brain network function in migraine, and investigate the persistence of such an effect following treatment discontinuation.MethodsThis was a randomized, double-blind, placebo-controlled, multicenter trial with a crossover design performed in adult episodic migraine patients with previous treatment failure. Patients were randomized (1:1) to 12 weeks of erenumab 140 mg or placebo, followed by a 12-week crossover. Resting state (RS) functional connectivity (FC) changes of brain networks involved in migraine were investigated using a seed-based correlation approach.ResultsSixty-one patients were randomized to treatment. In each treatment sequence, 27 patients completed the visit at week 12. Forty-four enrolled patients, 22 in each treatment sequence, completed the study procedures with no major protocol violations. We observed a carry-over effect of erenumab during the placebo treatment and therefore data analysis was performed as a parallel comparison of erenumab vs placebo of the first 12 weeks of treatment. From baseline to week 12, compared to placebo, patients receiving erenumab showed RS FC changes within the cerebellar, thalamic and periaqueductal gray matter networks, significantly associated with clinical improvement. Compared to non-responders, patients achieving a 50% reduction in migraine days had distinct patterns of thalamic and visual network RS FC. Brain RS FC changes reversed when erenumab was stopped. A lower baseline RS FC of the pontine network identified patients responding to erenumab.ConclusionErenumab modulates RS FC of networks involved in migraine pathophysiology. In line with clinical response, erenumab-induced brain RS FC changes tend to reverse when treatment is stopped.

Human anterior thalamic stimulation evoked cortical potentials align with intrinsic functional connectivity

Characterizing human thalamocortical network is fundamental for understanding a vast array of human behaviors since the thalamus plays a central role in cortico-subcortical communication. Over the past few decades, advances in functional magnetic resonance imaging have allowed for spatial mapping of intrinsic resting-state functional connectivity (RSFC) between both cortical regions and in cortico-subcortical networks. Despite these advances, identifying the electrophysiological basis of human thalamocortical network architecture remains challenging. By leveraging stereoelectroencephalography electrodes temporarily implanted into distributed cortical regions and the anterior nucleus of the thalamus (ANT) of 10 patients with refractory focal epilepsy, we tested whether ANT stimulation evoked cortical potentials align with RSFC from the stimulation site, derived from a normative functional connectome (n = 1000). Our study identifies spatial convergence of ANT stimulation evoked cortical potentials and normative RSFC. Other than connections to the Papez circuit, the ANT was found to be closely connected to several distinct higher-order association cortices, including the precuneus, angular gyrus, dorsal lateral prefrontal cortex, and anterior insula. Remarkably, we found that the spatial distribution and magnitude of cortical-evoked responses to single-pulse electrical stimulation of the ANT aligned with the spatial pattern and strength of normative RSFC of the stimulation site. The present study provides electrophysiological evidence that stimulation evoked electrical activity flows along intrinsic brain networks connected on a thalamocortical level.

Altered resting-state functional connectivity patterns in late middle-aged and older adults with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is increasingly recognized as a risk factor for cognitive decline, and has been associated with structural brain alterations in regions relevant to memory processes and Alzheimer's disease. However, it is unclear whether OSA is associated with disrupted functional connectivity (FC) patterns between these regions in late middle-aged and older populations. Thus, we characterized the associations between OSA severity and resting-state FC between the default mode network (DMN) and medial temporal lobe (MTL) regions. Second, we explored whether significant FC changes differed depending on cognitive status and were associated with cognitive performance. Ninety-four participants [24 women, 65.7 ± 6.9 years old, 41% with Mild Cognitive Impairment (MCI)] underwent a polysomnography, a comprehensive neuropsychological assessment and a resting-state functional magnetic resonance imaging (MRI). General linear models were conducted between OSA severity markers (i.e., the apnea-hypopnea, oxygen desaturation and microarousal indices) and FC values between DMN and MTL regions using CONN toolbox. Partial correlations were then performed between OSA-related FC patterns and (i) OSA severity markers in subgroups stratified by cognitive status (i.e., cognitively unimpaired versus MCI) and (ii) cognitive scores in the whole sample. All analyzes were controlled for age, sex and education, and considered significant at a p < 0.05 threshold corrected for false discovery rate. In the whole sample, a higher apnea-hypopnea index was significantly associated with lower FC between (i) the medial prefrontal cortex and bilateral hippocampi, and (ii) the left hippocampus and both the posterior cingulate cortex and precuneus. FC patterns were not associated with the oxygen desaturation index, or micro-arousal index. When stratifying the sample according to cognitive status, all associations remained significant in cognitively unimpaired individuals but not in the MCI group. No significant associations were observed between cognition and OSA severity or OSA-related FC patterns. OSA severity was associated with patterns of lower FC in regions relevant to memory processes and Alzheimer's disease. Since no associations were found with cognitive performance, these FC changes could precede detectable cognitive deficits. Whether these FC patterns predict future cognitive decline over the long-term needs to be investigated.

Stability of specific personality network features corresponding to openness trait across different adult age periods: A machine learning analysis

The functional connectivity patterns of the brain during resting state are closely related to an individual's cognition, emotion, behavior, and social interactions, making it an important research method to measure personality traits in an unbiased way, replacing traditional paper-and-pencil tests. However, due to the dynamic nature of the brain, whether the changes in functional connectivity caused by age can stably map onto personality traits has not been previously investigated. This study focuses on whether network features that are significantly related to personality traits can effectively distinguish subjects with different personality traits, and whether these network features vary across different periods of adulthood. The study included 343 healthy adult participants, divided into early adulthood and middle adulthood groups according to the age threshold of 35. Resting-state functional magnetic resonance imaging (fMRI) and the Big Five personality questionnaire were collected. we investigated the relationship between personality traits and intrinsic whole-brain functional connectome. We then used support vector machine (SVM) to evaluate the performance of personality network features in distinguishing subjects with high and low scores in the early-adulthood sample, and cross-validated in the mid-adulthood sample. Additionally, edge-based analysis (NBS) was used to explore the stability of personality networks across the two age samples. Our results show that the network features corresponding to openness personality trait are stable and can effectively differentiate subjects with different scores in both age samples. Furthermore, this study found that these network features vary to some extent across different periods of adulthood. These findings provide new evidence and insights into the application of resting-state functional connectivity patterns in measuring personality traits and help us better understand the dynamic characteristics of the human brain.

Functional and Structural Brain Abnormalities and Clinical Characteristics of Male Patients with Alcohol Dependence.

Even though many previous studies have reported structural or functional brain abnormalities in patients with alcohol dependence (ADPs), studies observing the structural and functional abnormalities associated with the clinical characteristics of ADPs utilizing a multimodal approach are still scarce. The aim of this study was to demonstrate structural and functional brain abnormalities and their association with the clinical characteristics of alcoholism in male ADPs. Fifteen healthy male controls (HCs) and 15 male ADPs who had been diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 5 criteria underwent T1-weighted imaging and resting-state functional magnetic resonance imaging (MRI) scans. The MRI data were postprocessed using statistical parametric mapping for structural analysis and CONN-fMRI functional connectivity (FC) tools for functional analysis. In comparison with male HCs, male ADPs were characterized by significantly reduced volumes of the white matter in the left globus pallidus (GP) (p-FDR < 0.05). This region affected the altered resting-state FC patterns in male ADPs. Interestingly, an abnormal FC in the precuneus and its positive correlation with the alcohol-use disorder identification test score were observed in ADPs (r = 0.546, p = 0.036). Based on the observations, it could be concluded that the GP serves as a neural marker that impacts abnormal functional networks in men with alcohol dependence. These findings have important clinical implications as they provide insights into the neural mechanism underlying the anatomical, functional, and clinical features of alcoholism.

Distinct resting-state functional connectivity patterns of Anterior Insula affected by smoking in mild cognitive impairment

Smoking is a modifiable risk factor for Alzheimer’s disease (AD). The insula plays a vital role in both smoking and cognition. However, the smoking effects on insula-related networks in cognitively normal controls (CN) and mild cognitive impairment (MCI) patients remain unknown. We identified 129 CN (85 non-smokers and 44 smokers) and 83 MCI (54 non-smokers and 29 smokers). Each underwent neuropsychological assessment and MRI (structural and resting-state functional). Seed-based functional analyses in the anterior and posterior insula were performed to calculate the functional connectivity (FC) with voxels in the whole brain. Mixed-effect analyses were performed to explore the interactive effects on smoking and cognitive status. Associations between FC and neuropsychological scales were assessed. Mixed-effect analyses revealed the FC differences between the right anterior insula (RAI) with the left middle temporal gyrus (LMTG) and that with the right inferior parietal lobule (RIPL) (p < 0.01, cluster level < 0.05, two-tailed, gaussian random field correction). The FC of RAI in both LMTG and RIPL sees a significant decrease in MCI smokers (p < 0.01). Smoking affects insula FC differently between MCI and CN, and could decrease the insula FC in MCI patients. Our study provides evidence of neural mechanisms between smoking and AD.

Multivariate resting-state functional connectomes predict and characterize obesity phenotypes.

The univariate obesity-brain associations have been extensively explored, while little is known about the multivariate associations between obesity and resting-state functional connectivity. We therefore utilized machine learning and resting-state functional connectivity to develop and validate predictive models of 4 obesity phenotypes (i.e. body fat percentage, body mass index, waist circumference, and waist-height ratio) in 3 large neuroimaging datasets (n = 2,992). Preliminary evidence suggested that the resting-state functional connectomes effectively predicted obesity/weight status defined by each obesity phenotype with good generalizability to longitudinal and independent datasets. However, the differences between resting-state functional connectivity patterns characterizing different obesity phenotypes indicated that the obesity-brain associations varied according to the type of measure of obesity. The shared structure among resting-state functional connectivity patterns revealed reproducible neuroimaging biomarkers of obesity, primarily comprising the connectomes within the visual cortex and between the visual cortex and inferior parietal lobule, visual cortex and orbital gyrus, and amygdala and orbital gyrus, which further suggested that the dysfunctions in the perception, attention and value encoding of visual information (e.g. visual food cues) and abnormalities in the reward circuit may act as crucial neurobiological bases of obesity. The recruitment of multiple obesity phenotypes is indispensable in future studies seeking reproducible obesity-brain associations.

Subacute changes in brain functional network connectivity after nocturnal sodium oxybate intake are associated with anterior cingulate GABA.

Sodium oxybate (γ-hydroxybutyrate, GHB) is an endogenous GHB/GABAB receptor agonist, clinically used to promote slow-wave sleep and reduce next-day sleepiness in disorders such as narcolepsy and fibromyalgia. The neurobiological signature of these unique therapeutic effects remains elusive. Promising current neuropsychopharmacological approaches to understand the neural underpinnings of specific drug effects address cerebral resting-state functional connectivity (rsFC) patterns and neurometabolic alterations. Hence, we performed a placebo-controlled, double-blind, randomized, cross-over pharmacological magnetic resonance imaging study with a nocturnal administration of GHB, combined with magnetic resonance spectroscopy of GABA and glutamate in the anterior cingulate cortex (ACC). In sum, 16 healthy male volunteers received 50mg/kg GHB p.o. or placebo at 02:30a.m. to maximize deep sleep enhancement and multi-modal brain imaging was performed at 09:00a.m. of the following morning. Independent component analysis of whole-brain rsFC revealed a significant increase of rsFC between the salience network (SN) and the right central executive network (rCEN) after GHB intake compared with placebo. This SN-rCEN coupling was significantly associated with changes in GABA levels in the ACC (pall < 0.05). The observed neural pattern is compatible with a functional switch to a more extrinsic brain state, which may serve as a neurobiological signature of the wake-promoting effects of GHB.

Occupation-modulated language networks and its lateralization: A resting-state fMRI study of seafarers.

Studies have revealed that the language network of Broca's area and Wernicke's area is modulated by factors such as disease, gender, aging, and handedness. However, how occupational factors modulate the language network remains unclear. In this study, taking professional seafarers as an example, we explored the resting-state functional connectivity (RSFC) of the language network with seeds (the original and flipped Broca's area and Wernicke's area). The results showed seafarers had weakened RSFC of Broca's area with the left superior/middle frontal gyrus and left precentral gyrus, and enhanced RSFC of Wernicke's area with the cingulate and precuneus. Further, seafarers had a less right-lateralized RSFC with Broca's area in the left inferior frontal gyrus, while the controls showed a left-lateralized RSFC pattern in Broca's area and a right-lateralized one in Wernicke's area. Moreover, seafarers displayed stronger RSFC with the left seeds of Broca's area and Wernicke's area. These findings suggest that years of working experience significantly modulates the RSFC of language networks and their lateralization, providing rich insights into language networks and occupational neuroplasticity.

Resting State Functional Connectivity is Associated With Treatment Response in Major Depression: A Real World Study

IntroductionMajor depressive disorder (MDD) is largely considered the most prevalent psychiatric disorder worldwide. Despite its domineering presence, effective treatment for many individuals remains elusive. Investigation into relevant biological markers, specifically neuroimaging correlates, of MDD and treatment response have gained traction in recent years; however, findings are still inconsistent.ObjectivesIn this study, we aimed to investigate the resting state functional connectivity patterns associated with treatment response in MDD inpatients in a real world setting.MethodsForty-three inpatients suffering from a major depressive episode were recruited from the psychiatric ward at IRCCS San Raffaele Hospital in Milan, Italy. Symptom severity was assessed via the 21-item Hamilton Depression Rating Scale (HDRS). The percentage of decrease in HDRS scores from admission to discharge was then calculated with the formula [(HDRS admission – HDRS discharge) * 100] / HDRS admission. All patients underwent a 3T MRI scan within one week of admission to acquire resting-state fMRI images, which included 200 sequential T2*-weighted volumes. Images were preprocessed using the CONN toolbox, running within Statistical Parametric Mapping (SPM 12). Preprocessing was performed according to a standard pipeline. A voxel-wise metric, intrinsic connectivity contrast (ICC), was implemented to explore the global resting state functional connectivity (rs-FC) patterns associated with treatment response. ICC-derived maps were then entered in the second-level analyses to examine the effect of the percentage of HDRS decrease, including age, sex, admission HDRS score, duration of hospitalization, and antidepressant dose equivalents as nuisance covariates.ResultsWe found that the percentage of HDRS decrease after treatment predicted rs-FC. ICC analysis identified 2 clusters where changes in HDRS scores were significantly associated with rs-FC, with increased connectivity in the supramarginal gyrus (pFDR = 0.002) and decreased connectivity in the amygdala and parahippocampal gyrus (pFDR = 0.047).ConclusionsOur results suggest that altered connectivity of the supramarginal gyrus, amygdala and parahippocampal gyrus is related to antidepressant treatment response. Given that these brain areas are implicated in emotional processing and mood, it is conceivable that a better integrity of brain connectivity may facilitate treatment response in major depression.Disclosure of InterestNone Declared

Altered electroencephalography resting state network coherence in remitted MDD

Individuals with remitted depression are at greater risk for subsequent depression and therefore may provide a unique opportunity to understand the neurophysiological correlates underlying the risk of depression. Research has identified abnormal resting-state electroencephalography (EEG) power metrics and functional connectivity patterns associated with major depression, however little is known about these neural signatures in individuals with remitted depression. We investigate the spectral dynamics of 64-channel EEG surface power and source-estimated network connectivity during resting states in 37 individuals with depression, 56 with remitted depression, and 49 healthy adults that did not differ on age, education, and cognitive ability across theta, alpha, and beta frequencies. Average reference spectral EEG surface power analyses identified greater left and midfrontal theta in remitted depression compared to healthy adults. Using Network Based Statistics, we also demonstrate within and between network alterations in LORETA transformed EEG source-space coherence across the default mode, fronto-parietal, and salience networks where individuals with remitted depression exhibited enhanced coherence compared to those with depression, and healthy adults. This work builds upon our currently limited understanding of resting EEG connectivity in depression, and helps bridge the gap between aberrant EEG power and brain network connectivity dynamics in this disorder. Further, our unique examination of remitted depression relative to both healthy and depressed adults may be key to identifying brain-based biomarkers for those at high risk for future, or subsequent depression.

Topological network properties of resting-state functional connectivity patterns are associated with metal mixture exposure in adolescents.

Adolescent exposure to neurotoxic metals adversely impacts cognitive, motor, and behavioral development. Few studies have addressed the underlying brain mechanisms of these metal-associated developmental outcomes. Furthermore, metal exposure occurs as a mixture, yet previous studies most often consider impacts of each metal individually. In this cross-sectional study, we investigated the relationship between exposure to neurotoxic metals and topological brain metrics in adolescents. In 193 participants (53% females, ages: 15-25 years) enrolled in the Public Health Impact of Metals Exposure (PHIME) study, we measured concentrations of four metals (manganese, lead, copper, and chromium) in multiple biological media (blood, urine, hair, and saliva) and acquired resting-state functional magnetic resonance imaging scans. Using graph theory metrics, we computed global and local efficiency (global:GE; local:LE) in 111 brain areas (Harvard Oxford Atlas). We used weighted quantile sum (WQS) regression models to examine association between metal mixtures and each graph metric (GE or LE), adjusted for sex and age. We observed significant negative associations between the metal mixture and GE and LE [βGE = -0.076, 95% CI (-0.122, -0.031); βLE= -0.051, 95% CI (-0.095, -0.006)]. Lead and chromium measured in blood contributed most to this association for GE, while chromium measured in hair contributed the most for LE. Our results suggest that exposure to this metal mixture during adolescence reduces the efficiency of integrating information in brain networks at both local and global levels, informing potential neural mechanisms underlying the developmental toxicity of metals. Results further suggest these associations are due to combined joint effects to different metals, rather than to a single metal.