Dataset Information

Pubertal maturation and sex effects on the default-mode network connectivity implicated in mood dysregulation.

ABSTRACT: This study examines the effects of puberty and sex on the intrinsic functional connectivity (iFC) of brain networks, with a focus on the default-mode network (DMN). Consistently implicated in depressive disorders, the DMN's function may interact with puberty and sex in the development of these disorders, whose onsets peak in adolescence, and which show strong sex disproportionality (females > males). The main question concerns how the DMN evolves with puberty as a function of sex. These effects are expected to involve within- and between-network iFC, particularly, the salience and the central-executive networks, consistent with the Triple-Network Model. Resting-state scans of an adolescent community sample (n = 304, male/female: 157/147; mean/std age: 14.6/0.41 years), from the IMAGEN database, were analyzed using the AFNI software suite and a data reduction strategy for the effects of puberty and sex. Three midline regions (medial prefrontal, pregenual anterior cingulate, and posterior cingulate), within the DMN and consistently implicated in mood disorders, were selected as seeds. Within- and between-network clusters of the DMN iFC changed with pubertal maturation differently in boys and girls (puberty-X-sex). Specifically, pubertal maturation predicted weaker iFC in girls and stronger iFC in boys. Finally, iFC was stronger in boys than girls independently of puberty. Brain-behavior associations indicated that lower connectivity of the anterior cingulate seed predicted higher internalizing symptoms at 2-year follow-up. In conclusion, weaker iFC of the anterior DMN may signal disconnections among circuits supporting mood regulation, conferring risk for internalizing disorders.

SUBMITTER: Ernst M

PROVIDER: S-EPMC6389927 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Pubertal maturation and sex effects on the default-mode network connectivity implicated in mood dysregulation.

Ernst Monique M Benson Brenda B Artiges Eric E Gorka Adam X AX Lemaitre Herve H Lago Tiffany T Miranda Ruben R Banaschewski Tobias T Bokde Arun L W ALW Bromberg Uli U Brühl Rüdiger R Büchel Christian C Cattrell Anna A Conrod Patricia P Desrivières Sylvane S Fadai Tahmine T Flor Herta H Grigis Antoine A Gallinat Juergen J Garavan Hugh H Gowland Penny P Grimmer Yvonne Y Heinz Andreas A Kappel Viola V Nees Frauke F Papadopoulos-Orfanos Dimitri D Penttilä Jani J Poustka Luise L Smolka Michael N MN Stringaris Argyris A Struve Maren M van Noort Betteke M BM Walter Henrik H Whelan Robert R Schumann Gunter G Grillon Christian C Martinot Marie-Laure Paillère MP Martinot Jean-Luc JL

Translational psychiatry 20190225 1

This study examines the effects of puberty and sex on the intrinsic functional connectivity (iFC) of brain networks, with a focus on the default-mode network (DMN). Consistently implicated in depressive disorders, the DMN's function may interact with puberty and sex in the development of these disorders, whose onsets peak in adolescence, and which show strong sex disproportionality (females > males). The main question concerns how the DMN evolves with puberty as a function of sex. These effects ...[more]

PMID: 30804326

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Project description:Women are more likely to have Alzheimer's disease (AD) and decline more rapidly once diagnosed despite greater verbal memory early in the disease compared to men-an advantage that has been termed "memory reserve." Resting state functional MRI (fMRI) investigations demonstrate interactions between sex and AD risk factors in default mode network (DMN) connectivity, a network of brain regions showing progressive dysfunction in AD. Separate work suggests connectivity of left prefrontal cortex (PFC) may correlate with more general cognitive reserve in healthy aging. It is unknown whether left prefrontal functional connectivity with anterior and posterior default mode network (aDMN, pDMN) might differ by sex in AD. This study employed group independent component analysis (ICA) to analyze resting state fMRI data from 158 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with baseline diagnoses of normal cognition or early mild cognitive impairment (eMCI). pDMN and aDMN were defined on a subject-specific basis; prefrontal areas were selected from the Brodmann atlas (BA 6, 44, 8, and 9). Moderation regression analyses examined whether sex and amyloid PET positivity (A+/-) moderated effects of apolipoprotein ε4 (APOE ε4) on connectivity between left PFC, aDMN, and pDMN; and between aDMN and pDMN. Significant analyses were followed up with partial correlations assessing relationship of connectivity to verbal memory on the Rey Auditory Verbal Learning Test (RAVLT), and with preliminary analyses within NC and eMCI groups separately. Results showed no sex moderation of effects of A+ and APOE ε4 on left prefrontal/DMN connectivity in the full sample. However, sex significantly moderated impact of A+ and APOE ε4 on connectivity between aDMN and pDMN (p < 0.01). Women with an APOE allele (ε4+) and A+ showed greater aDMN/pDMN connectivity than their ε4- counterparts. No significant results were observed in men. Subgroup analyses suggested the aDMN/pDMN finding was true for those with NC, not eMCI. Partial correlations controlling for age and education showed increased aDMN/pDMN connectivity related to better verbal learning in women (p < 0.01) and not men (p = 0.18). In women at risk for AD or in early symptomatic stages who also have evidence of amyloid burden, stronger aDMN/pDMN connectivity may support verbal learning.

Project description:Background: Numerous studies suggest a relationship between depression and metabolic syndrome, which is likely influenced by age. Interestingly, functional imaging analysis has shown an association between functional connectivity in the default mode network (DMN-FC) and components of metabolic syndrome, which is explored in this study. Methods: From a larger longitudinal cohort study on healthy aging, 943 individuals were extensively characterized for mood and cognition. Among these, 120 individuals who were selected for displaying extreme cognitive performance within the normal range (good and poor performers) were further studied. Here, in a cross-sectional design, using confirmatory factor analysis (CFA), the association between metabolic dysfunction and depressive mood as a function of age and its relationship with DMN-FC was studied. Results: Metabolic dysfunction was modeled as a second-order latent variable using CFA. First-order latent variables were obesity, glucose dysmetabolism, lipids imbalance, and blood pressure. Using multiple linear regression models, this study observed that metabolic dysfunction, glucose dysmetabolism, and lipids imbalance were linearly associated with depressive mood, and the association with obesity was U-shaped. The association of metabolic dysfunction, obesity, and glucose dysmetabolism with depressive mood is positive for the younger individuals in our sample and vanishes with aging. The FC of the right superior temporal gyrus with the DMN correlated with both obesity and depressive mood. In participants with higher obesity scores, FC increased with higher GDS scores, while in those with lower GDS scores, FC decreased. Age and blood pressure were associated with a more complex pattern of association between FC of the right supramarginal gyrus and GDS score. Conclusion: The association of metabolic dysfunction with depressive mood is influenced by age and relates with differential patterns of DMN-FC. The combination of the effects of age, mood, and metabolic dysfunction is likely to explain the heterogeneity of DMN-FC, which deserves further investigation with larger and longitudinal studies.

Project description:IntroductionAspects of the built environment relate to health factors and equity in living conditions, and may contribute to racial, ethnic, or economic health disparities. For example, urbanicity is linked with negative factors including exposure to gray space (e.g., impervious surfaces such as concrete, streets, or rooftops). While there is existing research on access to green space and urbanicity on some mental health and cognitive outcomes, there is limited research on the presence of gray space linked with cognitive functioning in youth. The goal of this study was to investigate the link between gray space and amygdala-default mode network (DMN) connectivity.MethodsThis study used data from the ABCD Study. Participants (n = 10,144; age M = 119.11 months, female = 47.62%) underwent resting-state fMRI acquisition at baseline. Impervious surfaces (gray space) were measured via the Child Opportunity Index (COI). To examine the relationship between presence of gray space and -amygdala-DMN (left/right) connectivity, we employed linear mixed effects models. Correlations were run between amygdala-DMN connectivity and internalizing and externalizing symptoms. Finally, post hoc sensitivity analyses were run to assess the impact of race.ResultsMore gray space, adjusting for age, sex, and neighborhood-level variables, was significantly associated with increased left amygdala-DMN connectivity (p = 0.0001). This association remained significant after sensitivity analyses for race were completed (p = 0.01). No significant correlations were observed between amygdala-DMN and internalizing or externalizing symptoms.DiscussionFindings suggest gray space was linked with increased left amygdala-DMN connectivity, circuits that have been implicated in affective processing, emotion regulation, and psychopathology. Thus gray space may be related to alterations in connectivity that may enhance risk for emotion dysregulation. Future investigation of these relationships is needed, as neuroimaging findings may represent early dysregulation not yet observed in the behavioral analyses at this age (i.e., the present study did not find significant relationships with parent-reported behavioral outcomes). These findings can help to inform future public policy on improving lived and built environments.

Project description:The default mode network (DMN) mediates self-awareness and introspection, core components of human consciousness. Therapies to restore consciousness in patients with severe brain injuries have historically targeted subcortical sites in the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia, with the goal of reactivating cortical DMN nodes. However, the subcortical connectivity of the DMN has not been fully mapped, and optimal subcortical targets for therapeutic neuromodulation of consciousness have not been identified. In this work, we created a comprehensive map of DMN subcortical connectivity by combining high-resolution functional and structural datasets with advanced signal processing methods. We analyzed 7 Tesla resting-state functional MRI (rs-fMRI) data from 168 healthy volunteers acquired in the Human Connectome Project. The rs-fMRI blood-oxygen-level-dependent (BOLD) data were temporally synchronized across subjects using the BrainSync algorithm. Cortical and subcortical DMN nodes were jointly analyzed and identified at the group level by applying a novel Nadam-Accelerated SCAlable and Robust (NASCAR) tensor decomposition method to the synchronized dataset. The subcortical connectivity map was then overlaid on a 7 Tesla 100 µm ex vivo MRI dataset for neuroanatomic analysis using automated segmentation of nuclei within the brainstem, thalamus, hypothalamus, basal forebrain, and basal ganglia. We further compared the NASCAR subcortical connectivity map with its counterpart generated from canonical seed-based correlation analyses. The NASCAR method revealed that BOLD signal in the central lateral nucleus of the thalamus and ventral tegmental area of the midbrain is strongly correlated with that of the DMN. In an exploratory analysis, additional subcortical sites in the median and dorsal raphe, lateral hypothalamus, and caudate nuclei were correlated with the cortical DMN. We also found that the putamen and globus pallidus are negatively correlated (i.e., anti-correlated) with the DMN, providing rs-fMRI evidence for the mesocircuit hypothesis of human consciousness, whereby a striatopallidal feedback system modulates anterior forebrain function via disinhibition of the central thalamus. Seed-based analyses yielded similar subcortical DMN connectivity, but the NASCAR result showed stronger contrast and better spatial alignment with dopamine immunostaining data. The DMN subcortical connectivity map identified here advances understanding of the subcortical regions that contribute to human consciousness and can be used to inform the selection of therapeutic targets in clinical trials for patients with disorders of consciousness.

Dataset Information

Pubertal maturation and sex effects on the default-mode network connectivity implicated in mood dysregulation.

Publications

Pubertal maturation and sex effects on the default-mode network connectivity implicated in mood dysregulation.

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