Resting-state Functional Connectivity Studies Research Articles

Fatigue and perceived energy in a sample of older adults over 10 years: A resting state functional connectivity study of neural correlates

PurposeDeclining energy and increasing fatigue, common in older age, predict neurodegenerative conditions, but their neural substrates are not known. We examined brain resting state connectivity in relation to declining self-reported energy levels (SEL) and occurrence of fatigue over time. MethodsWe examined resting-state functional MRI in 272 community dwelling older adults participating in the Health Aging and Body Composition Study (mean age 83 years; 57.4 % female; 40.8 % Black) with measures of fatigue and SEL collected at regular intervals over the prior ten years. Functional connectivity (FC) between cortex and striatum was examined separately for sensorimotor, executive, and limbic functional subregions. Logistic regression tested the association of FC in each network with prior fatigue state (reporting fatigue at least once or never reporting fatigue), and with SEL decline (divided into stable or declining SEL groups) and adjusted for demographic, physical function, mood, cognition, and comorbidities. ResultsHigher cortico-striatal FC in the right limbic network was associated with lower odds of reporting fatigue (better) at least once during the study period (adjusted odds ratio [95 % confidence interval], p-value: (0.747 [0.582, 0.955], 0.020), independent of SEL. Higher cortico-striatal FC in the right executive network was associated with higher odds of declining SEL (worse) during the study period (adjusted odds ratio [95 % confidence interval], p-value: (1.31 [1.01, 1.69], 0.041), independent of fatigue. Associations with other networks were not significant. ConclusionsIn this cohort of older adults, the cortico-striatal functional connectivity of declining SEL appears distinct from that underlying fatigue. Studies to further assess the neural correlates of energy and fatigue, and their independent contribution to neurodegenerative conditions are warranted.

A Study Over Brain Connectivity Network of Parkinson's Patients, Using Nonparametric Bayesian Model.

Parkinson disease is a neurodegenerative disease that disrupts functional brain networks. Many neurodegenerative disorders are associated with changes in brain communication patterns. Resting-state functional connectivity studies can distinguish the topological structure of Parkinson patients from healthy individuals by analyzing patterns between different regions of the brain. Accordingly, the present study aimed to determine the brain topological features and functional connectivity in patients with Parkinson disease, using a Bayesian approach. The data of this study were downloaded from the open neuro site. These data include resting-state functional magnetic resonance imaging (rs-fMRI) of 11 healthy individuals and 11 Parkinson patients with mean ages of 64.36 and 63.73, respectively. An advanced nonparametric Bayesian model was used to evaluate topological characteristics, including clustering of brain regions and correlation coefficient of the clusters. The significance of functional relationships based on each edge between the two groups was examined through false discovery rate (FDR) and network-based statistics (NBS) methods. Brain connectivity results showed a major difference in terms of the number of regions in each cluster and the correlation coefficient between the patient and healthy groups. The largest clusters in the patient and control groups were 26 and 53 regions, respectively, with clustering correlation values of 0.36 and 0.26. Although there are 15 common areas across the two clusters, the intensity of the functional relationship between these areas was different in the two groups. Moreover, using NBS and FDR methods, no significant difference was observed for each edge between the patient and healthy groups (P>0.05). The results of this study show a different topological configuration of the brain network between the patient and healthy groups, indicating changes in the functional relationship between a set of areas of the brain.

Amygdala fMRI-A Critical Appraisal of the Extant Literature.

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

Associations between cortisol stress responses and limbic volume and thickness in young adults: An exploratory study.

The investigation of the relationship between neural measures of limbic structures and hypothalamic pituitary adrenal axis responses to acute stress exposure in healthy young adults has so far focused in particular on task-based and resting state functional connectivity studies. Thus, the present study examined the association between limbic volume and thickness measures and acute cortisol responses to the psychosocial stress paradigm ScanSTRESS. Using Permutation Analysis of Linear Models controlling for sex, age and total brain volume, the associations between (sex-specific) cortisol increases and human connectome project style anatomical variables of limbic structures (i.e. volume and thickness) were investigated in 66 healthy and young (18-33 years) subjects (35 men, 31 women taking oral contraceptives). In addition, exploratory (sex-specific) bivariate correlations between cortisol increases and structural measures were conducted. The present data provide interesting new insights into the involvement of striato-limbic structures in psychosocial stress processing, suggesting that acute cortisol stress responses are also associated with mere structural measures of the human brain. Thus, our preliminary findings suggest that not only situation- and context-dependent reactions of the limbic system (i.e. blood oxygenation level-dependent reactions) are related to acute (sex-specific) cortisol stress responses but also basal and somewhat more constant structural measures. Our study hereby paves the way for further analyses in this context and highlights the relevance of the topic.

Resting-state functional connectivity-based parcellation of the human dentate nucleus: new findings and clinical relevance.

For years, the cerebellum was left out of functional magnetic resonance imaging (fMRI) studies due to technological limitations. The advent of novel data acquisition and reconstruction strategies (e.g., whole-brain simultaneous multi-slice imaging) employing multi-channel array coils has overcome such limitations, ushering unprecedented improvements in temporal signal-to-noise ratio and spatiotemporal resolution. Here, we aim to provide a brief report on the deep cerebellar nuclei, specifically focusing on the dentate nuclei, the primary output nuclei, situated within both cognitive and motor cerebello-cerebral circuits. We highlight the importance of functional parcellation in refining our understanding of broad resting-state functional connectivity (RSFC) in both health and disease. First, we review work relevant to the functional topography of the dentate nuclei, including recent advances in functional parcellation. Next, we review RSFC studies using the dentate nuclei as seed regions of interest in neurological and psychiatric populations and discuss the potential benefits of applying functionally defined subdivisions. Finally, we discuss recent technological advances and underscore ultrahigh-field neuroimaging as a tool to potentiate functionally parcellated RSFC analyses in clinical populations.

Altered within- and between-network functional connectivity in atypical Alzheimer's disease.

Posterior cortical atrophy and logopenic progressive aphasia are atypical clinical presentations of Alzheimer's disease. Resting-state functional connectivity studies have shown functional network disruptions in both phenotypes, particularly involving the language network in logopenic progressive aphasia and the visual network in posterior cortical atrophy. However, little is known about how connectivity differs both within and between brain networks in these atypical Alzheimer's disease phenotypes. A cohort of 144 patients was recruited by the Neurodegenerative Research Group at Mayo Clinic, Rochester, MN, USA, and underwent structural and resting-state functional MRI. Spatially preprocessed data were analysed to explore the default mode network and the salience, sensorimotor, language, visual and memory networks. The data were analysed at the voxel and network levels. Bayesian hierarchical linear models adjusted for age and sex were used to analyse within- and between-network connectivity. Reduced within-network connectivity was observed in the language network in both phenotypes, with stronger evidence of reductions in logopenic progressive aphasia compared to controls. Only posterior cortical atrophy showed reduced within-network connectivity in the visual network compared to controls. Both phenotypes showed reduced within-network connectivity in the default mode and sensorimotor networks. No significant change was noted in the memory network, but a slight increase in the salience within-network connectivity was seen in both phenotypes compared to controls. Between-network analysis in posterior cortical atrophy showed evidence of reduced visual-to-language network connectivity, with reduced visual-to-salience network connectivity, compared to controls. An increase in visual-to-default mode network connectivity was noted in posterior cortical atrophy compared to controls. Between-network analysis in logopenic progressive aphasia showed evidence of reduced language-to-visual network connectivity and an increase in language-to-salience network connectivity compared to controls. Findings from the voxel-level and network-level analysis were in line with the Bayesian hierarchical linear model analysis, showing reduced connectivity in the dominant network based on diagnosis and more crosstalk between networks in general compared to controls. The atypical Alzheimer's disease phenotypes were associated with disruptions in connectivity, both within and between brain networks. Phenotype-specific differences in connectivity patterns were noted in the visual network for posterior cortical atrophy and the language network for logopenic progressive aphasia.

Aberrant structural and functional alterations in postpartum depression: a combined voxel-based morphometry and resting-state functional connectivity study.

Postpartum depression (PPD) is a severe postpartum psychiatric disorder with unclear pathogenesis. Previous neuroimaging studies have reported structural or functional alterations in areas associated with emotion regulation, cognitive disorder, and parenting behaviors of PPD. The primary goal of this investigation was to explore the presence of brain structural alterations and relevant functional changes in PPD patients. A total of 28 patients and 30 matched healthy postnatal women (HPW) underwent both three-dimensional T1-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Structural analysis was performed by voxel-based morphometry (VBM), followed by resting-state functional analysis using a seed-based whole-brain functional connectivity (FC) approach with abnormal gray matter volume (GMV) regions as seed. Compared with HPW, the PPD patients showed increased GMV in the left dorsolateral prefrontal cortex (DLPFC.L), the right precentral gyrus (PrCG.R), and the orbitofrontal cortex (OFC). In the PPD group, the DLPFC.L showed increased FC with the right anterior cingulate and paracingulate gyri (ACG.R) and the right middle frontal gyrus (MFG.R); the FC between the PrCG.R and the right median cingulate and paracingulate gyri (DCG.R) exhibited enhanced; the OFC showed increased FC with MFG.R and the left inferior occipital gyrus (IOG.L). In PPD, GMV of DLPFC.L was positively correlated with EDPS scores (r = 0.409 p = 0.031), and FC of PrCG.R-DCG.R was positively correlated with EDPS scores (r = 0.483 p = 0.020). Structural and functional damage of the DLPFC.L and OFC is associated with cognitive disorders and parenting behaviors in PPD, while structural abnormalities of the DLPFC.L and PrCG.R are involved in impaired executive function. The increased GMV of DLPFC.L may be a unique structural pathological mechanism of PPD related to the inability of PPD patients to withstand long-term parenting stress. These findings have important implications for understanding neural mechanisms in PPD.

A Graph Theory Study of Resting-State Functional MRI Connectivity in Children With Carbon Monoxide Poisoning.

The effect of carbon monoxide (CO) poisoning on the topology of brain functional networks is unclear, especially in children whose brains are still developing. To investigate the topological alterations of the whole-brain functional connectome in children with CO poisoning and characterize its relationship with disease severity. Cross-sectional and prospective study. A total of 26 patients with CO poisoning and 26 healthy controls. A 3.0 T MRI system/echo planar imaging (EPI) and 3D brain volume imaging (BRAVO) sequences. We used the network-based statistics (NBS) method to explore between-group differences in functional connectivity strength and a graph-theoretical-based analytic method to explore the topology of brain networks. Student's t-test, chi-square test, NBS, Pearson correlation coefficient, and false discovery rate correction. The statistical significance threshold was set at P < 0.05. The case group's brain functional network topology was impaired in comparison to the control group (reduced global efficiency and small-worldness, increased characteristic path length). According to node and edge analyses, the case group showed topologically damaged regions in the frontal lobe and basal ganglia, as well as neuronal circuits with weaker connections. Also, there was a significant correlation between the patients' coma time and the degree (r = -0.4564), efficiency (r = -0.4625), and characteristic path length (r = 0.4383) of the nodes in the left orbital inferior frontal gyrus. Carbon monoxide hemoglobin content (COHb) concentration and right rolandic operculum node characteristic path length (r = -0.3894) were significantly correlated. The node efficiency and node degree of the right middle frontal gyrus (r = 0.4447 and 0.4539) and right pallidum (r = 0.4136 and 0.4501) significantly correlated with the MMSE score. The brain network topology of CO poisoned children is damaged, which is manifested by reduced network integration and may lead to a series of clinical symptoms in patients. 2. Stage 2.

A longitudinal mediation study of peer victimization and resting-state functional connectivity as predictors of development of adolescent psychopathology.

Peer victimization (PV) is associated with alterations in neural responses in regions subserving emotional regulatory processes and with increased risk of psychopathology during adolescence. The present study examined the longitudinal mediating effects of resting-state functional connectivity (rsFC) between adolescent PV and subsequent internalizing (depression and anxiety), and externalizing (conduct and hyperactivity/inattention) symptoms. 151 adolescents (baseline mean age 12-14; 54% males) were assessed and imaged three times during a five-year period. We focused on rsFC of a priori determined Regions-of-Interest (ROIs) guided by the literature (i.e., amygdala, anterior and posterior insula, anterior cingulate cortex, and medial prefrontal cortex). Multilevel mediation (MLM) analyses simultaneously examined the between-person, concurrent within-person, and lagged within-person associations between PV and internalizing/externalizing symptoms through changes in couplings of the amygdala with the other four ROIs. All models controlled for the effects of self-reported childhood maltreatment and sex differences. An increased rsFC of the amygdala-posterior insula significantly mediated the lagged within-person association of PV and internalizing symptoms (β = 0.144; 95% CI [0.018, 0.332]). This effect was significant regardless of childhood maltreatment, concurrent externalizing symptoms, and sex differences. The rsFC did not mediate the relationship between PV and externalizing symptoms. Results of this study suggest that adolescent PV may lead to long-lasting maladaptive neural communication between emotional response and sensory perception of pain (i.e., bottom-up emotion regulation) and that these neural responses may serve as unique markers for increased internalizing symptoms that appear in later adolescence in peer-victimized youth. These findings have implications for interventions targeting internalizing symptoms in victimized adolescents.

Internet addiction-induced brain structure and function alterations: a systematic review and meta-analysis of voxel-based morphometry and resting-state functional connectivity studies.

Internet addiction (IA) is a growing social concern and has been intensively studied in recent years. Previous imaging studies have shown that IA may impair brain structure and function, but with no robust conclusions. We conducted a systematic review and meta-analysis of neuroimaging studies in IA. Two separate meta-analyses were conducted for voxel-based morphometry (VBM) studies and resting-state functional connectivity (rsFC) studies. All meta-analyses were performed using two analysis methods activation likelihood estimation (ALE) and seed-based d mapping with permutation of subject images (SDM-PSI). The ALE analysis of VBM studies revealed less gray matter volume (GMV) in the supplementary motor area (SMA) (1176 mm3), anterior cingulate cortex (ACC) (one cluster size is 744 mm3 and the other is 688 mm3), and orbitofrontal cortex (OFC) (624 mm3) in subjects with IA. The SDM-PSI analysis showed less GMV in the ACC (56 voxels). The ALE analysis of rsFC studies showed stronger rsFC from posterior cingulate cortex (PCC) (880 mm3) or insula (712 mm3) to the whole brain in subjects with IA; however, the SDM-PSI analysis revealed no obvious rsFC alteration. These changes may underlie the core symptoms of IA, which include emotional regulation disorder, distraction, and impaired executive control. Our results reflect the common features of neuroimaging studies related to IA in recent years and may potentially help inform the development of more effective diagnostic and treatment approaches.

Mesoscale functional connectivity in macaque visual areas

Studies of resting-state functional connectivity (rsFC) have provided rich insights into the structures and functions of the human brain. However, most rsFC studies have focused on large-scale brain connectivity. To explore rsFC at a finer scale, we used intrinsic signal optical imaging to image the ongoing activity of the anesthetized macaque visual cortex. Differential signals from functional domains were used to quantify network-specific fluctuations. In 30–60 min resting-state imaging, a series of coherent activation patterns were observed in all three visual areas we examined (V1, V2, and V4). These patterns matched the known functional maps (ocular dominance, orientation, color) obtained in visual stimulation conditions. These functional connectivity (FC) networks fluctuated independently over time and exhibited similar temporal characteristics. Coherent fluctuations, however, were observed from orientation FC networks in different areas and even across two hemispheres. Thus, FC in the macaque visual cortex was fully mapped both on a fine scale and over a long range. Hemodynamic signals can be used to explore mesoscale rsFC in a submillimeter resolution.

An examination of the reliability of seed-to-seed resting state functional connectivity in tinnitus patients

Resting state functional connectivity (RS-FC) studies of tinnitus over the years have produced inconsistent results. While findings can be organized into broad categories, such as increased correlations between auditory and limbic areas in tinnitus patients and a disrupted default mode network, there has been little one-to-one correspondence of results across RS-FC studies of tinnitus. While some of this variation can be explained by the heterogeneity of the tinnitus population, including tinnitus severity, the sources of variability in RS-FC of tinnitus patients are unclear. To directly assess the reliability of RS-FC measures in tinnitus, both tinnitus and control participants from two different sites (University of Illinois at Urbana-Champaign, or UIUC, and the Wilford Hall Ambulatory Surgical Center, or WHASC, at the Lackland Airforce Base in San Antonio, Texas) participated in two resting state MRI scans separated by exactly one week. Seed-to-seed analysis assessing correlations between the fMRI activity of 27 regions in the default mode, dorsal attention, auditory, visual, salience, and emotional processing networks were examined in control and tinnitus participants separately for each site. Additionally, heart rate and respiration measures were collected at UIUC, and the effect of extra physiological corrections using these measures on reliability was examined within the UIUC participants. Intra-class correlation coefficients (ICCs) were used as the measure of reliability. Overall, RS-FC in a seed-to-seed analysis was as reliable in tinnitus participants as it was in control participants in the seed regions examined. As previously shown in studies of participants with normal hearing sensitivity, intra-network reliability was higher than inter-network reliability. Related to this, stronger correlations between two seed regions were predictive of stronger reliability of the connectivity between those regions. These effects were seen in both control and tinnitus populations. Additional physiological corrections did not have a significant impact on the ICC values. The current study demonstrates that, on a whole-brain level, RS-FC assessed via seed-to-seed analysis is reliable in tinnitus participants. We therefore must look to other sources as potential causes of discrepancies across studies, such as variability within analysis techniques or within the behavioral characteristics of tinnitus participants.

Structural and Functional Neural Alterations in Internet Addiction: A Study Protocol for Systematic Review and Meta-Analysis.

A growing number of neuroimaging studies have revealed abnormal brain structural and functional alterations in subjects with internet addiction (IA), however, with conflicting conclusions. We plan to conduct a systematic review and meta-analysis on the studies of voxelbased morphometry (VBM) and resting-state functional connectivity (rsFC), to reach a consolidated conclusion and point out the future direction in this field. A comprehensive search of rsFC and VBM studies of IA will be conducted in the PubMed, Cochrane Library, and Web of Science databases to retrieve studies published from the inception dates to August 2021. If the extracted data are feasible, activation likelihood estimation and seed-based d mapping methods will be used to meta-analyze the brain structural and functional changes in IA patients. This study will hopefully reach a consolidated conclusion on the impact of IA on human brain or point out the future direction in this field.

Clarifying the role of Cortico-Cortical and Amygdalo-Cortical brain dysconnectivity associated with Conduct Problems

A recent meta-analysis of resting-state functional connectivity studies revealed that individuals exhibiting antisocial behaviors or conduct problems may show disrupted brain connectivity in networks underpinning socio-affective and attentional processes. However, studies included in the meta-analysis generally rely on small sample sizes and substantially differ in terms of psychometric scales and neuroimaging methodologies. Therefore, we aimed to identify reliable functional brain connectivity alterations associated with severity of conduct problems using a large sample of adolescents and two measures of conduct problems. In a sample of 1416 children and adolescents, mass-univariate analyses of connectivity measures between 333 cortical parcels were conducted to examine the relationship between resting-state functional cortical-cortical connectome and the severity of conduct problems using the Child Behavior Checklist (CBCL) and the Strengths and Difficulties Questionnaire (SDQ). At a liberal threshold, results showed that the functional brain connectivity significantly associated with conduct problems largely differ between the two scales. Indeed, only 21 pairs of brain regions overlapped between the CBCL and SDQ. Permutation feature importance of these 21 brain connectivity measures revealed that connectivity between precentral/postcentral gyri and lateral prefrontal cortex (both ventral and dorsal) were the most important features in explaining variance in conduct problems. The current study highlights that psychometric measures may yield distinct functional connectivity results. Moreover, severity of conduct problems in children and adolescents was mainly associated with deficient functional connectivity of somatomotor and ventral attention networks indicating potential alterations in motor, cognitive and reward processes.

Different functional alteration in attention-deficit/hyperactivity disorder across developmental age groups: A meta-analysis and an independent validation of resting-state functional connectivity studies.

Attention-deficit/hyperactivity disorder (ADHD) is a highly complex and heterogeneous disorder. Abnormal brain connectivity in ADHD might be influenced by developmental ages which might lead to the lacking of significant spatial convergence across studies. However, the developmental patterns and mechanisms of ADHD brain connectivity remain to be fully uncovered. In the present study, we searched PubMed, Scopus, Web of Science, and Embase for seed-based whole-brain resting-state functional connectivity studies of ADHD published through October 12th, 2020. The seeds meeting inclusion criteria were categorized into the cortex group and subcortex group, as previous studies suggested that the cortex and subcortex have different temporal patterns of development. Activation likelihood estimation meta-analysis was performed to investigate the abnormal connectivity in different age groups (all-age group, younger: <12 years, older: ≥12 years). Moreover, significant convergence of reported foci was used as seeds for validation with our independent dataset. As with previous studies, scarce results were found in the all-age group. However, we found that the younger group consistently exhibited hyper-connectivity between different parts of the cortex and left middle frontal gyrus, and hypo-connectivity between different parts of the cortex and left putamen/pallidus/amygdala. Whereas, the older group (mainly for adults) showed hyper-connectivity between the cortex and right precuneus/sub-gyral/cingulate gyrus. Besides, the abnormal cortico-cortical and cortico-subcortical functional connectivity in children, and the abnormal cortico-cortical functional connectivity in adults were verified in our independent dataset. Our study emphasizes the importance of developmental age effects on the study of brain networks in ADHD. Further, we proposed that cortico-cortical and cortico-subcortical connectivity might play an important role in the pathophysiology of children with ADHD, while abnormal cortico-cortical connections were more important for adults with ADHD. This work provided a potential new insight to understand the neurodevelopmental mechanisms and possible clinical application of ADHD.

The Vestibulocerebellum and the Shattered Self: a Resting-State Functional Connectivity Study in Posttraumatic Stress Disorder and Its Dissociative Subtype

The flocculus is a region of the vestibulocerebellum dedicated to the coordination of neck, head, and eye movements for optimal posture, balance, and orienting responses. Despite growing evidence of vestibular and oculomotor impairments in the aftermath of traumatic stress, little is known about the effects of chronic psychological trauma on vestibulocerebellar functioning. Here, we investigated alterations in functional connectivity of the flocculus at rest among individuals with post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS) as compared to healthy controls. Forty-four healthy controls, 57 PTSD, and 32 PTSD + DS underwent 6-min resting-state MRI scans. Seed-based functional connectivity analyses using the right and left flocculi as seeds were performed. These analyses revealed that, as compared to controls, PTSD and PTSD + DS showed decreased resting-state functional connectivity of the left flocculus with cortical regions involved in bodily self-consciousness, including the temporo-parietal junction, the supramarginal and angular gyri, and the superior parietal lobule. Moreover, as compared to controls, the PTSD + DS group showed decreased functional connectivity of the left flocculus with the medial prefrontal cortex, the precuneus, and the mid/posterior cingulum, key regions of the default mode network. Critically, when comparing PTSD + DS to PTSD, we observed increased functional connectivity of the right flocculus with the right anterior hippocampus, a region affected frequently by early life trauma. Taken together, our findings point toward the crucial role of the flocculus in the neurocircuitry underlying a coherent and embodied self, which can be compromised in PTSD and PTSD + DS.

Hormone-based models for comparing menstrual cycle and hormonal contraceptive effects on human resting-state functional connectivity

Oral contraceptives (OCs) are widely used yet understudied given their potential for public health consequences. Emerging investigations scaling from single-subject, dense-sampling neuroimaging studies to population-level metrics have linked OCs to altered brain structure and function. Modeling the hypogonadal, hypergonadal, or mixed state effects of OCs in terms of their impact on hormone action in the brain is a valuable approach to synthesizing results across neuroimaging studies and comparing OC effects to companion findings from research on menstrual cycle phase effects on brain anatomy and function. Resting-state functional connectivity studies provide a powerful tool to evaluate the role of OCs on the intrinsic network connectivity that underlies multiple behavioral domains. The preponderance (but not consensus) of the current literature indicates that (1) as the menstrual cycle proceeds from a low to high progesterone state, prefrontal connectivity increases and parietal connectivity decreases; (2) OCs tend to mimic this connectivity pattern; therefore (3) OCs may produce a hyperprogestogenic state in the brain, in spite of overall reductions in endogenous steroid hormone levels. Alternative models are also considered.

Altered functional connectivity in common resting-state networks in patients with major depressive disorder: A resting-state functional connectivity study

The neural correlates of major depressive disorder (MDD) remain disputed. In the absence of reliable biological markers, the dysfunction and interaction of neural networks have been proposed as pathophysiological neural mechanisms in depression. Here, we examined the functional connectivity (FC) of brain networks. 51 healthy volunteers (mean age 33.57 ± 7.80) and 55 individuals diagnosed with MDD (mean age 33.89 ± 11.00) participated by performing a resting-state (rs) fMRI scan. Seed to voxel FC analyses were performed. Compared to healthy control (HC), MDD patients showed higher connectivity between the hippocampus and the anterior cingulate cortex (ACC) and lower connectivity between the insula and the ACC. The MDD group displayed lower connectivity between the inferior parietal lobule (IPL) and the superior frontal gyrus (SFG). The current data replicate previous findings regarding the cortico-limbic network (hippocampus – ACC connection) and the salience network (insula - ACC connection) and provide novel insight into altered rsFC in MDD, in particular involving the hippocampus - ACC and the insula - ACC connection. Furthermore, altered connectivity between the IPL and SFG indicates that the processing in higher cognitive processes such as attention and working memory is affected in MDD. These data further support dysfunctional neuronal networks as an interesting pathophysiological marker in depression.

Shared network-level functional alterations across substance use disorders: A multi-level kernel density meta-analysis of resting-state functional connectivity studies.

An increasing number of neuroimaging studies indicate functional alterations in cortico-striatal loops in individuals with substance use disorders (SUD). Dysregulations in these circuits may contribute to drug-seeking and drug-consuming behaviour by impeding inhibitory control, habit formation, and reward processing. Despite evidence of network-level changes in SUD, a shared pattern of functional alterations within and between spatially distributed brain networks has not been systematically investigated. The present meta-analytic investigation aims at identifying common alterations in resting-state functional connectivity patterns across different SUD, including stimulant, heroin, alcohol, cannabis, and nicotine use. To this aim, seed-based whole-brain connectivity maps for different functional networks were extracted and subjected to multi-level kernel density analysis to identify dysfunctional networks in individuals with SUD compared with healthy controls. In addition, an exploratory analysis examined substance-specific effects as well as the influence of drug use status on the main findings. Our findings indicate a hypoconnectivity pattern for the limbic, salience, and frontoparietal networks in individuals with SUD as compared with healthy controls. The default mode network additionally exhibited a complex pattern of hypo- and hyperconnectivity across the studies. The observed disrupted connectivity between networks in SUD may associate with deficient inhibitory control mechanisms that are thought to contribute to excessive craving and automatic drug-related behaviour as well as failure in substance use cessation. The identified network-based alterations in SUD represent potential treatment targets for neuromodulation, for example, network-based real-time functional magnetic resonance imaging (fMRI) neurofeedback. Such interventions can evaluate the behavioural relevance of the identified neural circuits.

Youth with Down syndrome display widespread increased functional connectivity during rest

Studies of resting-state functional connectivity in young people with Down syndrome (DS) have yielded conflicting results. Some studies have found increased connectivity while others have found a mix of increased and decreased connectivity. No studies have examined whole-brain connectivity at the voxel level in youth with DS during an eyes-open resting-state design. Additionally, no studies have examined the relationship between connectivity and network selectivity in youth with DS. Thus, the current study sought to fill this gap in the literature. Nineteen youth with DS (Mage = 16.5; range 7–23; 13 F) and 33 typically developing (TD) youth (Mage = 17.5; range 6–24; 18 F), matched on age and sex, completed a 5.25-min eyes-open resting-state fMRI scan. Whole-brain functional connectivity (average Pearson correlation of each voxel with every other voxel) was calculated for each individual and compared between groups. Network selectivity was then calculated and correlated with functional connectivity for the DS group. Results revealed that whole-brain functional connectivity was significantly higher in youth with DS compared to TD controls in widespread regions throughout the brain. Additionally, participants with DS had significantly reduced network selectivity compared to TD peers, and selectivity was significantly related to connectivity in all participants. Exploratory behavioral analyses revealed that regions showing increased connectivity in DS predicted Verbal IQ, suggesting differences in connectivity may be related to verbal abilities. These results indicate that network organization is disrupted in youth with DS such that disparate networks are overly connected and less selective, suggesting a potential target for clinical interventions.