Medial Default Mode Network Research Articles

Functional connectivity of the default mode network in first-episode drug-naïve patients with major depressive disorder

BackgroundAlterations in the default mode network (DMN) have been reported in major depressive disorder (MDD), well-replicated robust alterations of functional connectivity (FC) of DMN remain to be established. Investigating the functional connections of DMN at the overall and subsystem level in early MDD patients has the potential to advance our understanding of the physiopathology of this disorder. MethodsWe recruited 115 first-episode drug-naïve patients with MDD and 137 demographic-matched healthy controls (HCs). We first compared FC within the DMN, within/between the DMN subsystems, and from DMN subsystems to the whole brain between groups. Subsequently, we explored correlations between clinical features and identified alterations in FC. ResultsFirst-episode drug-naïve patients with MDD showed significantly increased FC within the DMN, dorsal DMN and medial DMN. Each subsystem showed a distinct FC pattern with other brain networks. Increased FC between the subsystems (core DMN, dorsal DMN) and other networks was associated with more severe depressive symptoms, while medial DMN-related connectivity correlated with memory performance. LimitationsThe relatively large “pure” MDD sample could only be generalized to a limited population. And, atypical asymmetric FCs in the DMN related to MDD might be missed for only left-lateralized ROIs were used to avoid strong correlations between mirrored (right/left) seed regions. ConclusionThese findings suggest patients with early MDD showed distinct patterns of FC alterations throughout DMN and its subsystems, which were related to illness severity and illness-associated cognitive impairment, highlighting their clinical significance.

Acute Stress Increases Striatal Connectivity With Cortical Regions Enriched for μ and κ Opioid Receptors

BackgroundUnderstanding the neurobiological effects of stress is critical for addressing the etiology of major depressive disorder (MDD). Using a dimensional approach involving individuals with differing degree of MDD risk, we investigated 1) the effects of acute stress on cortico-cortical and subcortical-cortical functional connectivity (FC) and 2) how such effects are related to gene expression and receptor maps. MethodsAcross 115 participants (37 control, 39 remitted MDD, 39 current MDD), we evaluated the effects of stress on FC during the Montreal Imaging Stress Task. Using partial least squares regression, we investigated genes whose expression in the Allen Human Brain Atlas was associated with anatomical patterns of stress-related FC change. Finally, we correlated stress-related FC change maps with opioid and GABAA (gamma-aminobutyric acid A) receptor distribution maps derived from positron emission tomography. ResultsResults revealed robust effects of stress on global cortical connectivity, with increased global FC in frontoparietal and attentional networks and decreased global FC in the medial default mode network. Moreover, robust increases emerged in FC of the caudate, putamen, and amygdala with regions from the ventral attention/salience network, frontoparietal network, and motor networks. Such regions showed preferential expression of genes involved in cell-to-cell signaling (OPRM1, OPRK1, SST, GABRA3, GABRA5), similar to previous genetic MDD studies. ConclusionsAcute stress altered global cortical connectivity and increased striatal connectivity with cortical regions that express genes that have previously been associated with imaging abnormalities in MDD and are rich in μ and κ opioid receptors. These findings point to overlapping circuitry underlying stress response, reward, and MDD.

Atypical Interpersonal Problem-Solving and Resting-state Functional Connectivity in Adolescents with Maltreatment Experience.

Childhood maltreatment is associated with altered neurocognitive functioning, which is thought to reflect, in part, adaptation to early adverse environmental experiences. However, we continue to lack a precise mechanistic understanding linking atypical neurocognitive processing with social functioning and psychiatric outcomes following early adversity. The present work investigated interpersonal problem-solving, resting-state functional connectivity (rsFC), and mental health symptoms in adolescents with documented maltreatment experience and explored whether altered neural function contributes in part to poorer social functioning. Forty adolescents (aged 12-17) with documented experiences of abuse or neglect and a carefully matched group of 42 non-maltreated peers participated in this study that measured task-based interpersonal problem-solving skills and rsFC. Adolescents with maltreatment experience showed poorer interpersonal problem-solving performance, which partly accounted for their elevated mental health symptoms. Resting-state seed-based analyses revealed that adolescents with maltreatment experience showed a significant increase in rsFC between medial Default Mode Network (DMN) hubs, the medial prefrontal cortex (mPFC), with a posterior cluster, including the posterior cingulate cortex (PCC), precuneus (PCu), retrosplenial cortex (RSC), and lingual gyrus (LG). Moderation analyses revealed that maltreatment-related increased DMN rsFC partly accounted for poorer performance in interpersonal problem-solving. Poorer interpersonal problem-solving, partly accounted for by atypical coupling between DMN medial hubs, was associated with maltreatment exposure. Interventions tailored to enhance interpersonal problem-solving represents a promising avenue to promote resilience and reduce the likelihood of mental health disorder following maltreatment experience.

0133 Sleeping Well or Sleeping Poorly: Clues from Brain Neurochemistry

Abstract Introduction Sleep problems are prevalent throughout the population, but little is known about the brain mechanisms that differentiate good and poor sleepers. We studied the association between brain neurochemistry, as measured by proton magnetic resonance spectroscopy (1H-MRS), and sleep quality as measured by actigraphy. We hypothesized that better sleep quality would be predicted by brain metabolites indicative of greater neuronal health, neural inhibition, and reduced levels of excitatory neurotransmitters. Methods 24 healthy adults (12 females25.4±5.6 years) wore an actigraph for seven consecutive days to collect Time in Bed (TIB), Total Sleep Time (TST), Sleep Efficiency (SE), Sleep Onset Latency (SOL), and Wake After Sleep Onset (WASO), and underwent 1H-MRS neuroimaging at 3T. Metabolite data from the medial prefrontal cortex (mPFC), dorsolateral prefrontal cortex (dlPFC), and medial parietal-occipital cortex (P-OCC) were entered stepwise into a series of multiple linear regression models to predict each actigraphic outcome. Results For SE, the regression analysis yielded a significant three predictor model (adjusted R2=.59), p=.0001, including mPFC choline (Cho; β=-.60), P-OCC N-Acetylaspartate (NAA ; β=.56), and P-OCC glutamate+glutamine (Glx; β=-.33). Better SE was associated with a combination of decreased Cho within the mPFC, and increased NAA and decreased Glx within the P-OCC. SOL was predicted by mPFC Cho alone (β =.60; adjusted R2 = .33), p=.002. This suggests that greater Cho within the mPFC was associated with a longer latency to fall asleep. Finally, for WASO, the regression analysis yielded a significant two predictor model, (adjusted R2 = .39), p=.002, including mPFC Cho (β = .56), P-OCC NAA (β = -.41). This suggests that a combination of greater Cho within the mPFC and decreased NAA in the P-OCC was associated with more minutes of wake after sleep onset. Conclusion Sleep quality was predicted from brain metabolites within the medial default mode network (DMN), an interconnected system of cortical regions that is normally deactivated during effortful cognitive processing. Sleep quality was predicted by a combined pattern of metabolites consistent with greater neuronal integrity, reduced cellular turnover, and lower excitatory neurotransmitters. Findings suggest potential metabolic and neuroanatomic targets for enhancing brain health to facilitate sleep quality. Support (If Any)

Gender- and Age-Specific Differences in Resting-State Functional Connectivity of the Central Autonomic Network in Adulthood.

Previous functional imaging studies have identified the role of central autonomic network (CAN) in autonomic regulation during various tasks. However, its variability with respect to gender and age, particularly in the resting state, remains poorly understood. Therefore, in this study we systematically investigated gender- and age-related differences in the resting-state functional connectivity (rsFC) seeded from core regions of this network, namely posterior mid-cingulate gyrus (pMCC), left amygdala, right anterior and left posterior insula, and ventromedial prefrontal cortex (vmPFC), using a large cross-sectional adulthood sample. Results revealed that each of the seeded connectivity maps engaged in at least one of the large-scale brain networks including sensorimotor, attentional, basal ganglia, limbic, and default mode networks (DMN). In the early-adulthood stage, females had stronger negative rsFC in pMCC and right anterior INS (aINS) with the medial DMN than males, possibly reflecting their greater suppression of the sympathoexcitation associated with sex hormonal estrogen. Whereas in the late-adulthood stage, they showed stronger positive rsFC in pMCC with postcentral gyrus and weaker negative rsFC with the most DMN, possibly relating to their higher risk of depression, anxiety, and dementia than males after menopause. Moreover, females demonstrated reduced negative rsFC in pMCC with dorsal PCUN/PCC and left AG with advancing age, whereas males showed the opposite pattern, namely increased positive rsFC, in pMCC with right SMG, and in vmPFC with ventral PCUN. We interpret these results as their differences of altered autonomic regulation associated with pain experience and reflective movement, respectively, due to aging. In sum, our findings add in literature that autonomic responses can be also represented intrinsically in the resting brain, and gender- and age-related differences might be associated with sex hormones and sensorimotor abilities, respectively.

Heritability of the limbic networks.

Individual differences in cognitive ability and social behaviour are influenced by the variability in the structure and function of the limbic system. A strong heritability of the limbic cortex has been previously reported, but little is known about how genetic factors influence specific limbic networks. We used diffusion tensor imaging tractography to investigate heritability of different limbic tracts in 52 monozygotic and 34 dizygotic healthy adult twins. We explored the connections that contribute to the activity of three distinct functional limbic networks, namely the dorsal cingulum (‘medial default-mode network’), the ventral cingulum and the fornix (‘hippocampal-diencephalic-retrosplenial network’) and the uncinate fasciculus (‘temporo-amygdala-orbitofrontal network’). Genetic and environmental variances were mapped for multiple tract-specific measures that reflect different aspects of the underlying anatomy. We report the highest heritability for the uncinate fasciculus, a tract that underpins emotion processing, semantic cognition, and social behaviour. High to moderate genetic and shared environmental effects were found for pathways important for social behaviour and memory, for example, fornix, dorsal and ventral cingulum. These findings indicate that within the limbic system inheritance of specific traits may rely on the anatomy of distinct networks and is higher for fronto-temporal pathways dedicated to complex social behaviour and emotional processing.