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White matter microstructure contributes to age-related declines in task-induced deactivation of the default mode network.

Brown CA, Hakun JG, Zhu Z, Johnson NF, Gold BT - Front Aging Neurosci (2015)

Bottom Line: Older adults are known to show reductions in deactivation of the DMN compared to younger adults.Critically, mediation analyses indicated that age-related reductions in WM microstructure accounted for the relationship between age and DMN deactivation in the more difficult mixed condition.These findings suggest that age-related declines in anatomical connectivity between DMN regions contribute to functional dysregulation within the DMN in older adults.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA.

ABSTRACT
Task-induced deactivations within the brain's default mode network (DMN) are thought to reflect suppression of endogenous thought processes to support exogenous goal-directed task processes. Older adults are known to show reductions in deactivation of the DMN compared to younger adults. However, little is understood about the mechanisms contributing to functional dysregulation of the DMN in aging. Here, we explored the relationships between functional modulation of the DMN and age, task performance and white matter (WM) microstructure. Participants were 117 adults ranging from 25 to 83 years old who completed an fMRI task switching paradigm, including easy (single) and difficult (mixed) conditions, and underwent diffusion tensor imaging (DTI). The fMRI results revealed an age by condition interaction (β = -0.13, t = -3.16, p = 0.002) such that increasing age affected deactivation magnitude during the mixed condition (β = -0.29, t = -3.24 p = 0.002) but not the single condition (p = 0.58). Additionally, there was a WM by condition interaction (β = 0.10, t = 2.33, p = 0.02) such that decreasing WM microstructure affected deactivation magnitude during the mixed condition (β = 0.30, t = 3.42 p = 0.001) but not the single condition (p = 0.17). Critically, mediation analyses indicated that age-related reductions in WM microstructure accounted for the relationship between age and DMN deactivation in the more difficult mixed condition. These findings suggest that age-related declines in anatomical connectivity between DMN regions contribute to functional dysregulation within the DMN in older adults.

No MeSH data available.


Related in: MedlinePlus

Results of mediation analyses. (A) Results of Model 1: Age correlated with DMN deactivation in the mixed condition (dotted arrow), but only the indirect effect through WM microstructure was significant (shown by solid arrows). (B) Results of Model 2: FA in DMN-WM mask had a direct effect on DMN deactivation in the mixed condition (solid arrow), and the indirect effect through age was non-significant (shown by dotted arrow). For (A) and (B), values are standardized β-coefficients with significant β-values shown in bold. Total effect between the independent and dependent variable in the model are shown above the arrow, and the direct effect is shown beneath the arrow, N = 117.
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Figure 4: Results of mediation analyses. (A) Results of Model 1: Age correlated with DMN deactivation in the mixed condition (dotted arrow), but only the indirect effect through WM microstructure was significant (shown by solid arrows). (B) Results of Model 2: FA in DMN-WM mask had a direct effect on DMN deactivation in the mixed condition (solid arrow), and the indirect effect through age was non-significant (shown by dotted arrow). For (A) and (B), values are standardized β-coefficients with significant β-values shown in bold. Total effect between the independent and dependent variable in the model are shown above the arrow, and the direct effect is shown beneath the arrow, N = 117.

Mentions: Results of Model 1 (Figure 4A) indicated that the direct effect of age on magnitude of DMN deactivation (c’ = −0.18, 95% CI [−0.38, 0.02]) was not significant, but instead was accounted for by the significant indirect pathway through FA in the DMN-WM mask (ab = −0.11, 95% CI [−0.24, −0.004]). Importantly, results of Model 2 (Figure 4B) indicated that the direct effect of FA in the DMN-WM mask on DMN deactivation (c’ = 0.21, 95% CI [0.01, 0.41]) was not significantly mediated by age (ab = 0.09 [−0.002, 0.21]).


White matter microstructure contributes to age-related declines in task-induced deactivation of the default mode network.

Brown CA, Hakun JG, Zhu Z, Johnson NF, Gold BT - Front Aging Neurosci (2015)

Results of mediation analyses. (A) Results of Model 1: Age correlated with DMN deactivation in the mixed condition (dotted arrow), but only the indirect effect through WM microstructure was significant (shown by solid arrows). (B) Results of Model 2: FA in DMN-WM mask had a direct effect on DMN deactivation in the mixed condition (solid arrow), and the indirect effect through age was non-significant (shown by dotted arrow). For (A) and (B), values are standardized β-coefficients with significant β-values shown in bold. Total effect between the independent and dependent variable in the model are shown above the arrow, and the direct effect is shown beneath the arrow, N = 117.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4598480&req=5

Figure 4: Results of mediation analyses. (A) Results of Model 1: Age correlated with DMN deactivation in the mixed condition (dotted arrow), but only the indirect effect through WM microstructure was significant (shown by solid arrows). (B) Results of Model 2: FA in DMN-WM mask had a direct effect on DMN deactivation in the mixed condition (solid arrow), and the indirect effect through age was non-significant (shown by dotted arrow). For (A) and (B), values are standardized β-coefficients with significant β-values shown in bold. Total effect between the independent and dependent variable in the model are shown above the arrow, and the direct effect is shown beneath the arrow, N = 117.
Mentions: Results of Model 1 (Figure 4A) indicated that the direct effect of age on magnitude of DMN deactivation (c’ = −0.18, 95% CI [−0.38, 0.02]) was not significant, but instead was accounted for by the significant indirect pathway through FA in the DMN-WM mask (ab = −0.11, 95% CI [−0.24, −0.004]). Importantly, results of Model 2 (Figure 4B) indicated that the direct effect of FA in the DMN-WM mask on DMN deactivation (c’ = 0.21, 95% CI [0.01, 0.41]) was not significantly mediated by age (ab = 0.09 [−0.002, 0.21]).

Bottom Line: Older adults are known to show reductions in deactivation of the DMN compared to younger adults.Critically, mediation analyses indicated that age-related reductions in WM microstructure accounted for the relationship between age and DMN deactivation in the more difficult mixed condition.These findings suggest that age-related declines in anatomical connectivity between DMN regions contribute to functional dysregulation within the DMN in older adults.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, KY, USA.

ABSTRACT
Task-induced deactivations within the brain's default mode network (DMN) are thought to reflect suppression of endogenous thought processes to support exogenous goal-directed task processes. Older adults are known to show reductions in deactivation of the DMN compared to younger adults. However, little is understood about the mechanisms contributing to functional dysregulation of the DMN in aging. Here, we explored the relationships between functional modulation of the DMN and age, task performance and white matter (WM) microstructure. Participants were 117 adults ranging from 25 to 83 years old who completed an fMRI task switching paradigm, including easy (single) and difficult (mixed) conditions, and underwent diffusion tensor imaging (DTI). The fMRI results revealed an age by condition interaction (β = -0.13, t = -3.16, p = 0.002) such that increasing age affected deactivation magnitude during the mixed condition (β = -0.29, t = -3.24 p = 0.002) but not the single condition (p = 0.58). Additionally, there was a WM by condition interaction (β = 0.10, t = 2.33, p = 0.02) such that decreasing WM microstructure affected deactivation magnitude during the mixed condition (β = 0.30, t = 3.42 p = 0.001) but not the single condition (p = 0.17). Critically, mediation analyses indicated that age-related reductions in WM microstructure accounted for the relationship between age and DMN deactivation in the more difficult mixed condition. These findings suggest that age-related declines in anatomical connectivity between DMN regions contribute to functional dysregulation within the DMN in older adults.

No MeSH data available.


Related in: MedlinePlus