Change in prefrontal activity and executive functions after action-based cognitive remediation in bipolar disorder: a randomized controlled trial
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Change in prefrontal activity and executive functions after action-based cognitive remediation in bipolar disorder : a randomized controlled trial. / Ott, Caroline V.; Macoveanu, Julian; Bowie, Christopher R.; Fisher, Patrick M.; Knudsen, Gitte M.; Kessing, Lars V.; Miskowiak, Kamilla W.
In: Neuropsychopharmacology, Vol. 46, 2021, p. 1113–1121.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Change in prefrontal activity and executive functions after action-based cognitive remediation in bipolar disorder
T2 - a randomized controlled trial
AU - Ott, Caroline V.
AU - Macoveanu, Julian
AU - Bowie, Christopher R.
AU - Fisher, Patrick M.
AU - Knudsen, Gitte M.
AU - Kessing, Lars V.
AU - Miskowiak, Kamilla W.
PY - 2021
Y1 - 2021
N2 - Cognitive impairment is prevalent in bipolar disorder (BD) but treatments with pro-cognitive effects are lacking. Insight concerning the neurocircuitry of cognitive improvement could provide a biomarker for pro-cognitive effects to advance treatment development. The dorsal prefrontal cortex (dPFC) is a promising region for such treatment target engagement. The aim of this functional magnetic resonance imaging (fMRI) study was to examine the effects of action-based cognitive remediation (ABCR) on early change in the dPFC blood-oxygen-level-dependent response in patients with BD in remission, and whether the observed neural change predicted improved executive functions following 10 weeks of treatment. Forty-five participants with remitted BD (ABCR: n = 26, control treatment: n = 19) completed a spatial n-back working memory task during fMRI and executive function tasks outside the scanner before and after two weeks of ABCR/control treatment, and an additional assessment of executive function at treatment completion. Thirty-four healthy controls underwent a single fMRI and executive function assessment for baseline comparisons. We found an early reversal of pretreatment hypo-activity in the dorsolateral prefrontal cortex (dlPFC) following ABCR vs. control during both high-load (2-back > 1-back) working memory (WM) (F(1,43) = 5.69, p = 0.02, η2 = 0.12) and general WM (2-back > 0-back) (F(1,43) = 5.61, p = 0.02, η2 = 0.12). This dlPFC activity increase predicted improved executive functions at treatment completion (high-load WM: B = −0.45, p = 0.01, general WM: B = −0.41, p < 0.01), independent of changes in subsyndromal symptoms. In conclusion, early dPFC increase may provide a neurocircuitry-based biomarker for pro-cognitive effects. Future cognition trials should include fMRI assessments to confirm the validity of this putative biomarker model across disorders with cognitive impairment.
AB - Cognitive impairment is prevalent in bipolar disorder (BD) but treatments with pro-cognitive effects are lacking. Insight concerning the neurocircuitry of cognitive improvement could provide a biomarker for pro-cognitive effects to advance treatment development. The dorsal prefrontal cortex (dPFC) is a promising region for such treatment target engagement. The aim of this functional magnetic resonance imaging (fMRI) study was to examine the effects of action-based cognitive remediation (ABCR) on early change in the dPFC blood-oxygen-level-dependent response in patients with BD in remission, and whether the observed neural change predicted improved executive functions following 10 weeks of treatment. Forty-five participants with remitted BD (ABCR: n = 26, control treatment: n = 19) completed a spatial n-back working memory task during fMRI and executive function tasks outside the scanner before and after two weeks of ABCR/control treatment, and an additional assessment of executive function at treatment completion. Thirty-four healthy controls underwent a single fMRI and executive function assessment for baseline comparisons. We found an early reversal of pretreatment hypo-activity in the dorsolateral prefrontal cortex (dlPFC) following ABCR vs. control during both high-load (2-back > 1-back) working memory (WM) (F(1,43) = 5.69, p = 0.02, η2 = 0.12) and general WM (2-back > 0-back) (F(1,43) = 5.61, p = 0.02, η2 = 0.12). This dlPFC activity increase predicted improved executive functions at treatment completion (high-load WM: B = −0.45, p = 0.01, general WM: B = −0.41, p < 0.01), independent of changes in subsyndromal symptoms. In conclusion, early dPFC increase may provide a neurocircuitry-based biomarker for pro-cognitive effects. Future cognition trials should include fMRI assessments to confirm the validity of this putative biomarker model across disorders with cognitive impairment.
U2 - 10.1038/s41386-020-00901-7
DO - 10.1038/s41386-020-00901-7
M3 - Journal article
C2 - 33168945
AN - SCOPUS:85095715683
VL - 46
SP - 1113
EP - 1121
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
ER -
ID: 251943722