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Disturbed cortico–amygdalar functional connectivity as pathophysiological correlate of working memory deficits in bipolar affective disorder

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Abstract

Patients suffering from bipolar affective disorder show deficits in working memory functions. In a previous functional magnetic resonance imaging study, we observed an abnormal hyperactivity of the amygdala in bipolar patients during articulatory rehearsal in verbal working memory. In the present study, we investigated the dynamic neurofunctional interactions between the right amygdala and the brain systems that underlie verbal working memory in both bipolar patients and healthy controls. In total, 18 euthymic bipolar patients and 18 healthy controls performed a modified version of the Sternberg item-recognition (working memory) task. We used the psychophysiological interaction approach in order to assess functional connectivity between the right amygdala and the brain regions involved in verbal working memory. In healthy subjects, we found significant negative functional interactions between the right amygdala and multiple cortical brain areas involved in verbal working memory. In comparison with the healthy control subjects, bipolar patients exhibited significantly reduced functional interactions of the right amygdala particularly with the right-hemispheric, i.e., ipsilateral, cortical regions supporting verbal working memory. Together with our previous finding of amygdala hyperactivity in bipolar patients during verbal rehearsal, the present results suggest that a disturbed right-hemispheric “cognitive–emotional” interaction between the amygdala and cortical brain regions underlying working memory may be responsible for amygdala hyperactivation and affects verbal working memory (deficits) in bipolar patients.

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Acknowledgments

This work was partially supported by the Deutsche Forschungsgemeinschaft (DFG) via the Clinical Research Group 241 “Genotype-phenotype relationships and neurobiology of the longitudinal course of psychosis” (http://www.kfo241.de; Grant Number GR 1950/5-1) to O.G..

Conflicts of interest

O.G. was honorary speaker for the following companies: Astra Zeneca, Bristol Myers Squibb, Janssen Cilag, Lilly, Otsuka and Servier. He has been invited to scientific congresses by Astra Zeneca, Janssen Cilag and Pfizer and has received a research grant from Servier. O.G. reports that these potential conflicts have no relation to the subject of the present study. All other authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. University Hospital of Psychiatry, University of Bern, Bern, Switzerland

    Katharina Stegmayer

  2. Centre for Translational Research in Systems Neuroscience and Clinical Psychiatry, Georg August University, Goettingen, Germany

    Juliana Usher, Sarah Trost & Oliver Gruber

  3. Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany

    Ilona Henseler

  4. Central Institute of Mental Health, Mannheim, Germany

    Heike Tost & Marcella Rietschel

  5. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University, Munich, Germany

    Peter Falkai

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  1. Katharina Stegmayer
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  2. Juliana Usher
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  3. Sarah Trost
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  4. Ilona Henseler
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  5. Heike Tost
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  6. Marcella Rietschel
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  8. Oliver Gruber
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Correspondence to Oliver Gruber.

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Katharina Stegmayer and Juliana Usher contributed equally to this work.

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Stegmayer, K., Usher, J., Trost, S. et al. Disturbed cortico–amygdalar functional connectivity as pathophysiological correlate of working memory deficits in bipolar affective disorder. Eur Arch Psychiatry Clin Neurosci 265, 303–311 (2015). https://doi.org/10.1007/s00406-014-0517-5

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