TY - JOUR
T1 - Impact of childhood adversity on network reconfiguration dynamics during working memory in hypogonadal women
AU - Shanmugan, Sheila
AU - Cao, Wen
AU - Satterthwaite, Theodore D.
AU - Sammel, Mary D.
AU - Ashourvan, Arian
AU - Bassett, Danielle S.
AU - Ruparel, Kosha
AU - Gur, Ruben C.
AU - Epperson, C. Neill
AU - Loughead, James
N1 - Funding Information:
This research was supported by P50 MH099910 (Epperson), Penn PROMOTES Research on Sex and Gender in Health (Epperson), K12 HD085848 (Epperson), R01 AG030641 and R01 AG048839 (Epperson), R01MH107703 (Satterthwaite), R01MH113550 (Satterthwaite and Bassett), R01MH107235 (Gur), F30AG055256 (Shanmugan) and R25MH119043. Bassett acknowledges support from the Alfred P. Sloan Foundation , the ISI Foundation , and the John D. and Catherine T. MacArthur Foundation . Dr. Epperson reports that she has received funding from Shire Pharmaceuticals for investigator initiated research and is site investigator for a multi-site, randomized clinical trial funded by Sage Therapeutics. Dr. Epperson consults to Sage Therapeutics and Shire and discloses personal and/or family investments in the following companies; BMS, Johnson and Johnson, Merck, Abbott, and Abbvie.
PY - 2020/9
Y1 - 2020/9
N2 - Many women with no history of cognitive difficulties experience executive dysfunction during menopause. Significant adversity during childhood negatively impacts executive function into adulthood and may be an indicator of women at risk of a mid-life cognitive decline. Previous studies have indicated that alterations in functional network connectivity underlie these negative effects of childhood adversity. There is growing evidence that functional brain networks are not static during executive tasks; instead, such networks reconfigure over time. Optimal dynamics are necessary for efficient executive function; while too little reconfiguration is insufficient for peak performance, too much reconfiguration (supra-optimal reconfiguration) is also maladaptive and associated with poorer performance. Here we examined the impact of adverse childhood experiences (ACEs) on network flexibility, a measure of dynamic reconfiguration, during a letter n-back task within three networks that support executive function: frontoparietal, salience, and default mode networks. Several animal and human subject studies have suggested that childhood adversity exerts lasting effects on executive function via serotonergic mechanisms. Tryptophan depletion (TD) was used to examine whether serotonin function drives ACE effects on network flexibility. We hypothesized that ACE would be associated with higher flexibility (supra-optimal flexibility) and that TD would further increase this measure. Forty women underwent functional imaging at two time points in this double-blind, placebo controlled, crossover study. Participants also completed the Penn Conditional Exclusion Test, a task assessing abstraction and mental flexibility. The effects of ACE and TD were evaluated using generalized estimating equations. ACE was associated with higher flexibility across networks (frontoparietal β = 0.00748, D = 2.79, p = 0.005; salience β = 0.00679, D = 3.02, p = 0.003; and default mode β = 0.00910, D = 3.53, p = 0.0004). While there was no interaction between ACE and TD, active TD increased network flexibility in both ACE groups in comparison to sham depletion (frontoparietal β = 0.00489, D = 2.15, p = 0.03; salience β = 0.00393, D = 1.91, p = 0.06; default mode β = 0.00334, D = 1.73, p = 0.08). These results suggest that childhood adversity has lasting impacts on dynamic reconfiguration of functional brain networks supporting executive function and that decreasing serotonin levels may exacerbate these effects.
AB - Many women with no history of cognitive difficulties experience executive dysfunction during menopause. Significant adversity during childhood negatively impacts executive function into adulthood and may be an indicator of women at risk of a mid-life cognitive decline. Previous studies have indicated that alterations in functional network connectivity underlie these negative effects of childhood adversity. There is growing evidence that functional brain networks are not static during executive tasks; instead, such networks reconfigure over time. Optimal dynamics are necessary for efficient executive function; while too little reconfiguration is insufficient for peak performance, too much reconfiguration (supra-optimal reconfiguration) is also maladaptive and associated with poorer performance. Here we examined the impact of adverse childhood experiences (ACEs) on network flexibility, a measure of dynamic reconfiguration, during a letter n-back task within three networks that support executive function: frontoparietal, salience, and default mode networks. Several animal and human subject studies have suggested that childhood adversity exerts lasting effects on executive function via serotonergic mechanisms. Tryptophan depletion (TD) was used to examine whether serotonin function drives ACE effects on network flexibility. We hypothesized that ACE would be associated with higher flexibility (supra-optimal flexibility) and that TD would further increase this measure. Forty women underwent functional imaging at two time points in this double-blind, placebo controlled, crossover study. Participants also completed the Penn Conditional Exclusion Test, a task assessing abstraction and mental flexibility. The effects of ACE and TD were evaluated using generalized estimating equations. ACE was associated with higher flexibility across networks (frontoparietal β = 0.00748, D = 2.79, p = 0.005; salience β = 0.00679, D = 3.02, p = 0.003; and default mode β = 0.00910, D = 3.53, p = 0.0004). While there was no interaction between ACE and TD, active TD increased network flexibility in both ACE groups in comparison to sham depletion (frontoparietal β = 0.00489, D = 2.15, p = 0.03; salience β = 0.00393, D = 1.91, p = 0.06; default mode β = 0.00334, D = 1.73, p = 0.08). These results suggest that childhood adversity has lasting impacts on dynamic reconfiguration of functional brain networks supporting executive function and that decreasing serotonin levels may exacerbate these effects.
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U2 - 10.1016/j.psyneuen.2020.104710
DO - 10.1016/j.psyneuen.2020.104710
M3 - Article
C2 - 32563173
AN - SCOPUS:85086603387
VL - 119
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
SN - 0306-4530
M1 - 104710
ER -