Changes in ventral prefrontal-subcortical network connectivity during the course of remission from bipolar mania

Background: Dysregulated ventral prefrontal-subcortical networks are implicated in bipolar disorder, although how connectivity changes within these networks during the emergence and resolution of affective episodes is unclear. To address this knowledge gap, in this post-hoc study, we investigated lo...

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Main Authors: Jennifer E. Siegel-Ramsay, Elizabeth Lippard, Thomas Blom, Wade Webber, Cal Adler, David E. Fleck, Melissa P. DelBello, Jorge R.C. Almeida, Stephen M. Strakowski
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Journal of Mood and Anxiety Disorders
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Online Access:http://www.sciencedirect.com/science/article/pii/S2950004425000288
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author Jennifer E. Siegel-Ramsay
Elizabeth Lippard
Thomas Blom
Wade Webber
Cal Adler
David E. Fleck
Melissa P. DelBello
Jorge R.C. Almeida
Stephen M. Strakowski
author_facet Jennifer E. Siegel-Ramsay
Elizabeth Lippard
Thomas Blom
Wade Webber
Cal Adler
David E. Fleck
Melissa P. DelBello
Jorge R.C. Almeida
Stephen M. Strakowski
author_sort Jennifer E. Siegel-Ramsay
collection DOAJ
description Background: Dysregulated ventral prefrontal-subcortical networks are implicated in bipolar disorder, although how connectivity changes within these networks during the emergence and resolution of affective episodes is unclear. To address this knowledge gap, in this post-hoc study, we investigated longitudinal changes in prefrontal-subcortical connectivity during remission from mania in individuals with bipolar I disorder. Methods: We followed 35 individuals with bipolar I disorder through eight weeks of treatment for a manic episode. Using mixed models, we compared changes in ventral prefrontal-subcortical connectivity between individuals who remitted (n = 16, Young Mania Rating Scale/Hamilton Depression Rating Scale < 10 by week eight) and those who did not (n = 19) during emotional distractor conditions of the continuous performance task (CPT-END), a cognitive attentional task with emotional and neutral distractors; at baseline, one and eight weeks of treatment covarying for age and sex. Results: During the eight-week trial, significant group-by-time interactions were found between medial prefrontal cortex and right inferior frontal gyrus pars triangularis. There was also a group-by-time interaction in connectivity between prefrontal cortex and left thalamus, bilateral amygdala, and pregenual anterior cingulate cortex. Conclusion: These results highlight distinct ventral prefrontal-subcortical connectivity patterns characterizing the remitted state in bipolar disorder during tasks requiring focused attention amid emotional distractions. In the context of previous research, remission was associated with more normative connectivity between medial prefrontal and both thalamus and ventrolateral prefrontal cortex. However, while ventral prefrontal–paralimbic/limbic connectivity may show improvement with symptom remission, it may not fully normalize, suggesting residual functional abnormalities despite clinical recovery.
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spelling doaj-art-bef69a4015664d9b8d317385ddf338522025-08-20T02:37:52ZengElsevierJournal of Mood and Anxiety Disorders2950-00442025-09-011110013110.1016/j.xjmad.2025.100131Changes in ventral prefrontal-subcortical network connectivity during the course of remission from bipolar maniaJennifer E. Siegel-Ramsay0Elizabeth Lippard1Thomas Blom2Wade Webber3Cal Adler4David E. Fleck5Melissa P. DelBello6Jorge R.C. Almeida7Stephen M. Strakowski8Department of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas, Austin, TX, USA; Correspondence to: Department of Psychiatry and Behavioral Sciences, Dell Medical School at the University of Austin. 1501 Red River St.,Austin, TX 78712.USA.Department of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas, Austin, TX, USADepartment of Psychiatry and Behavioral Neurosciences, University of Cincinnati College of Medicine, OH, USADepartment of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas, Austin, TX, USADepartment of Psychiatry and Behavioral Neurosciences, University of Cincinnati College of Medicine, OH, USADepartment of Psychiatry and Behavioral Neurosciences, University of Cincinnati College of Medicine, OH, USADepartment of Psychiatry and Behavioral Neurosciences, University of Cincinnati College of Medicine, OH, USADepartment of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas, Austin, TX, USADepartment of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas, Austin, TX, USA; Department of Psychiatry, Indiana University School of Medicine, Indiana University, Indianapolis, IN, USABackground: Dysregulated ventral prefrontal-subcortical networks are implicated in bipolar disorder, although how connectivity changes within these networks during the emergence and resolution of affective episodes is unclear. To address this knowledge gap, in this post-hoc study, we investigated longitudinal changes in prefrontal-subcortical connectivity during remission from mania in individuals with bipolar I disorder. Methods: We followed 35 individuals with bipolar I disorder through eight weeks of treatment for a manic episode. Using mixed models, we compared changes in ventral prefrontal-subcortical connectivity between individuals who remitted (n = 16, Young Mania Rating Scale/Hamilton Depression Rating Scale < 10 by week eight) and those who did not (n = 19) during emotional distractor conditions of the continuous performance task (CPT-END), a cognitive attentional task with emotional and neutral distractors; at baseline, one and eight weeks of treatment covarying for age and sex. Results: During the eight-week trial, significant group-by-time interactions were found between medial prefrontal cortex and right inferior frontal gyrus pars triangularis. There was also a group-by-time interaction in connectivity between prefrontal cortex and left thalamus, bilateral amygdala, and pregenual anterior cingulate cortex. Conclusion: These results highlight distinct ventral prefrontal-subcortical connectivity patterns characterizing the remitted state in bipolar disorder during tasks requiring focused attention amid emotional distractions. In the context of previous research, remission was associated with more normative connectivity between medial prefrontal and both thalamus and ventrolateral prefrontal cortex. However, while ventral prefrontal–paralimbic/limbic connectivity may show improvement with symptom remission, it may not fully normalize, suggesting residual functional abnormalities despite clinical recovery.http://www.sciencedirect.com/science/article/pii/S2950004425000288Bipolar disorder maniaLongitudinalTreatment responseFunctional connectivityVentral prefrontal cortex
spellingShingle Jennifer E. Siegel-Ramsay
Elizabeth Lippard
Thomas Blom
Wade Webber
Cal Adler
David E. Fleck
Melissa P. DelBello
Jorge R.C. Almeida
Stephen M. Strakowski
Changes in ventral prefrontal-subcortical network connectivity during the course of remission from bipolar mania
Journal of Mood and Anxiety Disorders
Bipolar disorder mania
Longitudinal
Treatment response
Functional connectivity
Ventral prefrontal cortex
title Changes in ventral prefrontal-subcortical network connectivity during the course of remission from bipolar mania
title_full Changes in ventral prefrontal-subcortical network connectivity during the course of remission from bipolar mania
title_fullStr Changes in ventral prefrontal-subcortical network connectivity during the course of remission from bipolar mania
title_full_unstemmed Changes in ventral prefrontal-subcortical network connectivity during the course of remission from bipolar mania
title_short Changes in ventral prefrontal-subcortical network connectivity during the course of remission from bipolar mania
title_sort changes in ventral prefrontal subcortical network connectivity during the course of remission from bipolar mania
topic Bipolar disorder mania
Longitudinal
Treatment response
Functional connectivity
Ventral prefrontal cortex
url http://www.sciencedirect.com/science/article/pii/S2950004425000288
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