scholarly journals 4386 Age-related Changes in the Functional Connectivity within the Default Mode Network

2020 ◽  
Vol 4 (s1) ◽  
pp. 44-44
Author(s):  
Cassandra Leonardo ◽  
Crystal G Franklin ◽  
Peter T Fox

OBJECTIVES/GOALS: To evaluate whether the default mode network experiences age-related changes in functional connectivity and to identify these patterns of progression across seven decades of life. The overall goal is to evaluate whether quantifying these functional changes can serve as potential neurobiomarkers of aging for further quantitative genetic analyses. METHODS/STUDY POPULATION: Scans were performed at the RII on a 3T Siemens Trio scanner with an 8-channel head coil. Whole-brain, rsfMR imaging was performed using a gradient-echo EPI sequence sensitive to the BOLD effect (TE/TR = 30/3000 ms; flip angle = 90°; isotropic 1.72 mm2). Subjects were instructed to lie in dimmed light with their eyes open and try not to fall asleep. Image analysis was performed with FMRIB’s Software Library tools (www.fmrib.ox.ac.uk/fsl). Preprocessing of resting state data includes motion correction, brain extraction, spatial smoothing, and high-pass temporal filtering. Time series data was extracted from 9 DMN ROIs using FSL’s Featquery tool with 6mm radius spherical ROI masks created in Mango. After extraction, DMN connectivity was assess using structural equation modeling implemented in Amos 22.0 (IBM, Inc.). RESULTS/ANTICIPATED RESULTS: The exploratory SEM (eSEM) default mode network (DMN) model used consists of 9 regions of interest and 13 functional connectivity paths. The eSEM DMN model exhibited exceptional model fit to a primary resting state data set of 1169 subjects from the Genetics of Brain Structure project (1R01MH078111-01, David Glahn PI) with an RMSEA of 0.037. This model also had excellent model fit in 7 cohorts that were grouped by decade age (10s – RMSEA: 0.058, 20s – 0.051, 30s – 0.045, 40s – 0.048, 50s – 0.043, 60s – 0.035, 70s – 0.037). Analysis of the decade group-wise path coefficients identified 7 of the 13 paths (pC -> LMTG, pC -> PCC, PCC -> MPFG, PCC -> vACC, MPFG -> vACC, LIPL -> RIPL, LMTG -> RMTG) significantly negatively correlated with age-related changes. As early as the 1st decade of life, the functional connectivity within the DMN decreases. DISCUSSION/SIGNIFICANCE OF IMPACT: The DMN experiences progressive age-related decreases in connectivity, beginning in the first decade of life. Our results suggest that DMN path coefficients can serve as biomarkers of cognitive aging, which can then be used as quantitative traits for genetic analyses to identify genes associated with normal aging and age-related cognitive diseases.

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Tiffany Bell ◽  
Akashroop Khaira ◽  
Mehak Stokoe ◽  
Megan Webb ◽  
Melanie Noel ◽  
...  

Abstract Background Migraine affects roughly 10% of youth aged 5–15 years, however the underlying mechanisms of migraine in youth are poorly understood. Multiple structural and functional alterations have been shown in the brains of adult migraine sufferers. This study aims to investigate the effects of migraine on resting-state functional connectivity during the period of transition from childhood to adolescence, a critical period of brain development and the time when rates of pediatric chronic pain spikes. Methods Using independent component analysis, we compared resting state network spatial maps and power spectra between youth with migraine aged 7–15 and age-matched controls. Statistical comparisons were conducted using a MANCOVA analysis. Results We show (1) group by age interaction effects on connectivity in the visual and salience networks, group by sex interaction effects on connectivity in the default mode network and group by pubertal status interaction effects on connectivity in visual and frontal parietal networks, and (2) relationships between connectivity in the visual networks and the migraine cycle, and age by cycle interaction effects on connectivity in the visual, default mode and sensorimotor networks. Conclusions We demonstrate that brain alterations begin early in youth with migraine and are modulated by development. This highlights the need for further study into the neural mechanisms of migraine in youth specifically, to aid in the development of more effective treatments.


2021 ◽  
Vol 15 ◽  
Author(s):  
Mohammad S. E. Sendi ◽  
Elaheh Zendehrouh ◽  
Charles A. Ellis ◽  
Zhijia Liang ◽  
Zening Fu ◽  
...  

Background: Schizophrenia affects around 1% of the global population. Functional connectivity extracted from resting-state functional magnetic resonance imaging (rs-fMRI) has previously been used to study schizophrenia and has great potential to provide novel insights into the disorder. Some studies have shown abnormal functional connectivity in the default mode network (DMN) of individuals with schizophrenia, and more recent studies have shown abnormal dynamic functional connectivity (dFC) in individuals with schizophrenia. However, DMN dFC and the link between abnormal DMN dFC and symptom severity have not been well-characterized.Method: Resting-state fMRI data from subjects with schizophrenia (SZ) and healthy controls (HC) across two datasets were analyzed independently. We captured seven maximally independent subnodes in the DMN by applying group independent component analysis and estimated dFC between subnode time courses using a sliding window approach. A clustering method separated the dFCs into five reoccurring brain states. A feature selection method modeled the difference between SZs and HCs using the state-specific FC features. Finally, we used the transition probability of a hidden Markov model to characterize the link between symptom severity and dFC in SZ subjects.Results: We found decreases in the connectivity of the anterior cingulate cortex (ACC) and increases in the connectivity between the precuneus (PCu) and the posterior cingulate cortex (PCC) (i.e., PCu/PCC) of SZ subjects. In SZ, the transition probability from a state with weaker PCu/PCC and stronger ACC connectivity to a state with stronger PCu/PCC and weaker ACC connectivity increased with symptom severity.Conclusions: To our knowledge, this was the first study to investigate DMN dFC and its link to schizophrenia symptom severity. We identified reproducible neural states in a data-driven manner and demonstrated that the strength of connectivity within those states differed between SZs and HCs. Additionally, we identified a relationship between SZ symptom severity and the dynamics of DMN functional connectivity. We validated our results across two datasets. These results support the potential of dFC for use as a biomarker of schizophrenia and shed new light upon the relationship between schizophrenia and DMN dynamics.


2021 ◽  
Author(s):  
Kaley Davis ◽  
Emily Hirsch ◽  
Dylan Gee ◽  
Margaret Andover ◽  
Amy Krain Roy

Abstract Humans are reliant on their caregivers for an extended period of time, offering numerous opportunities for environmental factors, such as parental attitudes and behaviors, to impact brain development. The default mode network is a neural system encompassing the medial prefrontal cortex, posterior cingulate cortex, precuneus, and temporo-parietal junction, which is implicated in aspects of cognition and psychopathology. Delayed default mode network maturation in children and adolescents has been associated with greater general dimensional psychopathology, and positive parenting behaviors have been suggested to serve as protective mechanisms against atypical default mode network development. The current study aimed to extend the existing research by examining whether within- default mode network resting-state functional connectivity would mediate the relation between parental acceptance/warmth and youth psychopathology. Data from the Adolescent Brain and Cognitive Development study, which included a community sample of 9,058 children ages 9-10.9 years, were analyzed to test this prediction. Results from the analysis demonstrated a significant mediation, where greater parental acceptance/warmth predicted greater within- default mode network resting-state functional connectivity, which in turn predicted lower psychopathology. Our study provides preliminary support for the notion that positive parenting traits may reduce the risk for psychopathology in youth through their influence on the default mode network. Due to the cross-sectional nature of this study, we can only draw correlational inference; therefore, these relationships should be tested longitudinally in future investigations.


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