Deficits in frontoparietal activation and anterior insula functional connectivity during regulation of cognitive-affective interference in bipolar disorder

Kristen K. Ellard, Aishwarya K. Gosai, Julia M. Felicione, Amy T. Peters, Conor V. Shea, Louisa G. Sylvia, Andrew A. Nierenberg, Alik S. Widge, Darin D. Dougherty, Thilo Deckersbach

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Objectives: Bipolar disorders (BD) are characterized by emotion and cognitive dysregulation. Mapping deficits in the neurocircuitry of cognitive-affective regulation allows for potential identification of intervention targets. This study used functional MRI data in BD patients and healthy controls during performance on a task requiring cognitive and inhibitory control superimposed on affective images, assessing cognitive and affective interference. Methods: Functional MRI data were collected from 39 BD patients and 36 healthy controls during performance on the Multi-Source Interference Task overlaid on images from the International Affective Picture System (MSIT-IAPS). Analyses examined patterns of activation in a priori regions implicated in cognitive and emotional processing. Functional connectivity to the anterior insula during task performance was also examined, given this region's role in emotion-cognition integration. Results: BD patients showed significantly less activation during cognitive interference trials in inferior parietal lobule, dorsomedial prefrontal cortex, anterior insula, mid-cingulate, and ventrolateral prefrontal cortex regardless of affective valence. BD patients showed deviations in functional connectivity with anterior insula in regions of the default mode and frontoparietal control networks during negatively valenced cognitive interference trials. Conclusions: Our findings show disruptions in cognitive regulation and inhibitory control in BD patients in the presence of irrelevant affective distractors. Results of this study suggest one pathway to dysregulation in BD is through inefficient integration of affective and cognitive information, and highlight the importance of developing interventions that target emotion-cognition integration in BD.

Original languageEnglish (US)
Pages (from-to)244-258
Number of pages15
JournalBipolar Disorders
Volume21
Issue number3
DOIs
StatePublished - May 2019
Externally publishedYes

Bibliographical note

Funding Information:
Dr. Ellard gratefully acknowledges support from the NIH National Institute of Neurological Disorders and Stroke (NINDS) Training Program in Recovery and Restoration of CNS Health and Function (T32 NS100663-01). Dr. Deckersbach gratefully acknowledges support from a NIMH-funded Mentored Patient Oriented Research Grant (K23 MH074895-01). Drs. Dougherty, Widge and Deckersbach acknowledge additional support from the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement Number W911NF-14-2-0045 issued by ARO contracting office in support of DARPA’s SUBNETS Program. The views, opinions, and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. Dr. Dougherty further acknowledges support from NIH grants (R01 MH045573-24) and (1R01AT008563-01A1) and Medtronic.

Funding Information:
National Institute of Neurological Disorders and Stroke (NINDS), Grant/ Award Number: T32 NS100663-01; NIMH, Grant/Award Number: K23 MH074895- 01; Defense Advanced Research Projects Agency (DARPA), Grant/Award Number: W911NF-14-2-0045; NIH, Grant/ Award Number: R01 MH045573-24 and 1R01AT008563-01A1; Medtronic

Funding Information:
No commercial funding to any contributing authors directly supported the preparation of this work. Additional funding disclosures: Dr Nierenberg reports grants and personal fees from Takeda/ Lundbeck and AlfaSigma (formerly known as PamLabs). He has received research funding from GlaxoSmithKlein, NeuroRx Pharma, Marriott Foundation, National Institute of Health, Brain & Behavior Research Foundation, Janssen, Intracellular Therapies, and Patient Centered Outcomes Research Institute (PCORI). Dr Nierenberg also receives personal or consulting fees from Alkermes, PAREXEL, Sunovian, Naurex, Hoffman La Roche/Genentech, Eli Lilly & Company, Pfizer, SLACK Publishing, and Physician’s Postgraduate Press, Inc Dr Van Dijk is currently employed by Pfizer Inc Pfizer Inc had no input or influence on the study design, data collection, data analyses, or interpretation of results. Dr Dougherty receives device donations and has received consulting income from Medtronic. Dr Dougherty has pending patent applications related to deep brain stimulation for mental illness. Dr Dougherty further reports consulting income from Insys, speaking fees from Johnson & Johnson, and research support from Cyberonics and Roche. Dr Deckersbach reports research support from Agency for Healthcare Research and Quality, National Institutes of Health, Defense Advanced Research

Funding Information:
Dr. Ellard gratefully acknowledges support from the NIH National Institute of Neurological Disorders and Stroke (NINDS) Training Program in Recovery and Restoration of CNS Health and Function (T32 NS100663-01). Dr. Deckersbach gratefully acknowledges support from a NIMH-funded Mentored Patient Oriented Research Grant (K23 MH074895-01). Drs. Dougherty, Widge and Deckersbach acknowledge additional support from the Defense Advanced Research Projects Agency (DARPA) under Cooperative Agreement Number W911NF-14-2-0045 issued by ARO contracting office in support of DARPA's SUBNETS Program. The views, opinions, and/or findings expressed are those of the author and should not be interpreted as representing the official views or policies of the Department of Defense or the U.S. Government. Dr. Dougherty further acknowledges support from NIH grants (R01 MH045573-24) and (1R01AT008563-01A1) and Medtronic.

Publisher Copyright:
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Keywords

  • Multi Source Interference Task
  • bipolar disorder
  • cognition
  • emotion regulation
  • fMRI

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