Reduced functional connectivity between ventromedial prefrontal cortex and insula relates to longer corrected QT interval in HIV+ and HIV− individuals

Roger C McIntosh, Dominic C. Chow, Corey J. Lum, Melissa Hidalgo, Cecilia M. Shikuma, Kalpana J. Kallianpur

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Objective Prolongation of the QT interval, i.e., measure of the time between the start of the Q wave and the end of the T wave, is a precursor to fatal cardiac arrhythmias commonly observed in individuals infected with the Human Immunodeficiency Virus (HIV), and is related to dysregulation of the autonomic nervous system. We investigated the relationship between QT interval length and resting state functional connectivity (rsFC) of the ventromedial prefrontal cortex (VMPFC), a core region of the brain that is involved with cardio-autonomic regulation. Method Eighteen HIV+ men on antiretroviral therapy and with no history of heart disease were compared with 26 HIV-negative control subjects who had similar demographic and cardio-metabolic characteristics. A seed-based rsFC analysis of the right and left VMPFC was performed at the individual subject level, and 2nd-level analyses were conducted to identify the following: group differences in connectivity, brain regions correlating with corrected (QTc) interval length before and after controlling for those group differences, and regions where seed-based rsFC correlates with CD4 count and QTc interval within HIV+ individuals. Results HIV-negative adults showed greater rsFC between the VMPFC seed regions and several default mode network structures. Across groups greater rsFC with the left anterior insula was associated with shorter QTc intervals, whereas right posterior insula connectivity with the VMPFC correlated with greater QTc intervals. HIV patients with lower CD4 counts and higher QTc intervals showed greater rsFC between the right VMPFC and the right posterior insula and dorsal cingulate gyrus. Conclusions This study demonstrates that QTc interval lengths are associated with distinct patterns of VMPFC rsFC with posterior and anterior insula. In HIV patients, longer QTc interval and lower CD4 count corresponded to weaker VMPFC connectivity with the dorsal striatrum. Significance A forebrain control mechanism may be implicated in the suppression of cardiovagal influence that confers risk for ventricular arrhythmias and sudden cardiac death in HIV+ individuals.

Original languageEnglish (US)
Pages (from-to)1839-1850
Number of pages12
JournalClinical Neurophysiology
Volume128
Issue number10
DOIs
StatePublished - Oct 1 2017

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Prefrontal Cortex
HIV
CD4 Lymphocyte Count
Seeds
Cardiac Arrhythmias
Gyrus Cinguli
Autonomic Nervous System
Sudden Cardiac Death
Brain
Prosencephalon
Heart Diseases
Demography

Keywords

  • Anterior insula
  • Central autonomic network
  • HIV
  • QTc prolongation
  • Resting state functional connectivity
  • Ventromedial prefrontal cortex

ASJC Scopus subject areas

  • Sensory Systems
  • Neurology
  • Clinical Neurology
  • Physiology (medical)

Cite this

Reduced functional connectivity between ventromedial prefrontal cortex and insula relates to longer corrected QT interval in HIV+ and HIV− individuals. / McIntosh, Roger C; Chow, Dominic C.; Lum, Corey J.; Hidalgo, Melissa; Shikuma, Cecilia M.; Kallianpur, Kalpana J.

In: Clinical Neurophysiology, Vol. 128, No. 10, 01.10.2017, p. 1839-1850.

Research output: Contribution to journalArticle

McIntosh, Roger C ; Chow, Dominic C. ; Lum, Corey J. ; Hidalgo, Melissa ; Shikuma, Cecilia M. ; Kallianpur, Kalpana J. / Reduced functional connectivity between ventromedial prefrontal cortex and insula relates to longer corrected QT interval in HIV+ and HIV− individuals. In: Clinical Neurophysiology. 2017 ; Vol. 128, No. 10. pp. 1839-1850.
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abstract = "Objective Prolongation of the QT interval, i.e., measure of the time between the start of the Q wave and the end of the T wave, is a precursor to fatal cardiac arrhythmias commonly observed in individuals infected with the Human Immunodeficiency Virus (HIV), and is related to dysregulation of the autonomic nervous system. We investigated the relationship between QT interval length and resting state functional connectivity (rsFC) of the ventromedial prefrontal cortex (VMPFC), a core region of the brain that is involved with cardio-autonomic regulation. Method Eighteen HIV+ men on antiretroviral therapy and with no history of heart disease were compared with 26 HIV-negative control subjects who had similar demographic and cardio-metabolic characteristics. A seed-based rsFC analysis of the right and left VMPFC was performed at the individual subject level, and 2nd-level analyses were conducted to identify the following: group differences in connectivity, brain regions correlating with corrected (QTc) interval length before and after controlling for those group differences, and regions where seed-based rsFC correlates with CD4 count and QTc interval within HIV+ individuals. Results HIV-negative adults showed greater rsFC between the VMPFC seed regions and several default mode network structures. Across groups greater rsFC with the left anterior insula was associated with shorter QTc intervals, whereas right posterior insula connectivity with the VMPFC correlated with greater QTc intervals. HIV patients with lower CD4 counts and higher QTc intervals showed greater rsFC between the right VMPFC and the right posterior insula and dorsal cingulate gyrus. Conclusions This study demonstrates that QTc interval lengths are associated with distinct patterns of VMPFC rsFC with posterior and anterior insula. In HIV patients, longer QTc interval and lower CD4 count corresponded to weaker VMPFC connectivity with the dorsal striatrum. Significance A forebrain control mechanism may be implicated in the suppression of cardiovagal influence that confers risk for ventricular arrhythmias and sudden cardiac death in HIV+ individuals.",
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AU - Hidalgo, Melissa

AU - Shikuma, Cecilia M.

AU - Kallianpur, Kalpana J.

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N2 - Objective Prolongation of the QT interval, i.e., measure of the time between the start of the Q wave and the end of the T wave, is a precursor to fatal cardiac arrhythmias commonly observed in individuals infected with the Human Immunodeficiency Virus (HIV), and is related to dysregulation of the autonomic nervous system. We investigated the relationship between QT interval length and resting state functional connectivity (rsFC) of the ventromedial prefrontal cortex (VMPFC), a core region of the brain that is involved with cardio-autonomic regulation. Method Eighteen HIV+ men on antiretroviral therapy and with no history of heart disease were compared with 26 HIV-negative control subjects who had similar demographic and cardio-metabolic characteristics. A seed-based rsFC analysis of the right and left VMPFC was performed at the individual subject level, and 2nd-level analyses were conducted to identify the following: group differences in connectivity, brain regions correlating with corrected (QTc) interval length before and after controlling for those group differences, and regions where seed-based rsFC correlates with CD4 count and QTc interval within HIV+ individuals. Results HIV-negative adults showed greater rsFC between the VMPFC seed regions and several default mode network structures. Across groups greater rsFC with the left anterior insula was associated with shorter QTc intervals, whereas right posterior insula connectivity with the VMPFC correlated with greater QTc intervals. HIV patients with lower CD4 counts and higher QTc intervals showed greater rsFC between the right VMPFC and the right posterior insula and dorsal cingulate gyrus. Conclusions This study demonstrates that QTc interval lengths are associated with distinct patterns of VMPFC rsFC with posterior and anterior insula. In HIV patients, longer QTc interval and lower CD4 count corresponded to weaker VMPFC connectivity with the dorsal striatrum. Significance A forebrain control mechanism may be implicated in the suppression of cardiovagal influence that confers risk for ventricular arrhythmias and sudden cardiac death in HIV+ individuals.

AB - Objective Prolongation of the QT interval, i.e., measure of the time between the start of the Q wave and the end of the T wave, is a precursor to fatal cardiac arrhythmias commonly observed in individuals infected with the Human Immunodeficiency Virus (HIV), and is related to dysregulation of the autonomic nervous system. We investigated the relationship between QT interval length and resting state functional connectivity (rsFC) of the ventromedial prefrontal cortex (VMPFC), a core region of the brain that is involved with cardio-autonomic regulation. Method Eighteen HIV+ men on antiretroviral therapy and with no history of heart disease were compared with 26 HIV-negative control subjects who had similar demographic and cardio-metabolic characteristics. A seed-based rsFC analysis of the right and left VMPFC was performed at the individual subject level, and 2nd-level analyses were conducted to identify the following: group differences in connectivity, brain regions correlating with corrected (QTc) interval length before and after controlling for those group differences, and regions where seed-based rsFC correlates with CD4 count and QTc interval within HIV+ individuals. Results HIV-negative adults showed greater rsFC between the VMPFC seed regions and several default mode network structures. Across groups greater rsFC with the left anterior insula was associated with shorter QTc intervals, whereas right posterior insula connectivity with the VMPFC correlated with greater QTc intervals. HIV patients with lower CD4 counts and higher QTc intervals showed greater rsFC between the right VMPFC and the right posterior insula and dorsal cingulate gyrus. Conclusions This study demonstrates that QTc interval lengths are associated with distinct patterns of VMPFC rsFC with posterior and anterior insula. In HIV patients, longer QTc interval and lower CD4 count corresponded to weaker VMPFC connectivity with the dorsal striatrum. Significance A forebrain control mechanism may be implicated in the suppression of cardiovagal influence that confers risk for ventricular arrhythmias and sudden cardiac death in HIV+ individuals.

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KW - Central autonomic network

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KW - Resting state functional connectivity

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