Roger C McIntosh1, Dominic C Chow2, Corey J Lum3, Melissa Hidalgo4, Cecilia M Shikuma2, Kalpana J Kallianpur5. 1. Department of Health Psychology, University of Miami, Coral Gables, FL 33124, USA. Electronic address: r.mcintosh@miami.edu. 2. Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI 96813, USA. 3. Hawaii Center for AIDS, Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI 96813, USA; Division of Cardiology, Department of Medicine, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI 96813, USA. 4. Department of Health Psychology, University of Miami, Coral Gables, FL 33124, USA. 5. Hawaii Center for AIDS, Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawai'i, Honolulu, HI 96813, USA.
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.
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. HIVpatients 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 HIVpatients, 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.