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

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.

Whole‐brain computational modeling reveals disruption of microscale brain dynamics in HIV infected individuals

“…A number of regions, including left opercular part of inferior frontal gyrus (pars opercularis), superior temporal gyrus, postcentral gyrus, pericalcarine cortex, right insula, and parahippocampal gyrus showed significant differences only in recurrent connections strength w . Some of these, such as the insula and parahippocampal gyrus have been shown to have reduced regional volume and FC in the HIV‐infected population (Kallianpur et al, 2012; McIntosh et al, 2017; Samboju et al, 2018). The balanced integration of excitatory and inhibitory synaptic currents in the local cortex allows the cortical network to operate at high efficiency of information transmission at a low energy cost (Yu, Shen, Wang, & Yu, 2018).…”

“…The lingual gyrus (part of the visual processing system) has also been previously reported to be affected in perinatally HIV-infected youths (Sarma et al, 2019). Ances et al (2009) shown to have reduced regional volume and FC in the HIV-infected population (Kallianpur et al, 2012;McIntosh et al, 2017;Samboju et al, 2018). The balanced integration of excitatory and inhibitory synaptic currents in the local cortex allows the cortical network to operate at high efficiency of information transmission at a low energy cost (Yu, Shen, Wang, & Yu, 2018).…”

Abnormal Dispersion of Ventricular Repolarization as a Risk Factor in Patients with Human Immunodeficiency Virus: Tp-e Interval, Tp-e/QTc Ratio

“…They have mentioned that the stimulation of the posterior insular cortex induced increasing degrees of atrioventricular block producing escape rhythms, premature ventricular contractions, QT prolongation, and ultimately death in asystole. More importantly, McIntosh et al [17] showed that QTc prolongation had an important association with distinct patterns of ventromedial prefrontal cortex state functional connectivity (rsFC) with the posterior and anterior insula. Longer QTc and lower CD4 count corresponded to weaker ventromedial prefrontal cortex connectivity with the dorsal striatum in patients with HIV.…”

Whole-brain computational modeling reveals disruption of microscale brain dynamics in HIV infected individuals

“…A number of regions, including left opercular part of inferior frontal gyrus (pars opercularis), superior temporal gyrus, postcentral gyrus, pericalcarine cortex, right insula, and parahippocampal gyrus showed significant differences only in recurrent connections strength w. Some of these, such as the insula and parahippocampal gyrus have been shown to have reduced regional volume and functional connectivity in the HIV-infected population (Kallianpur et al, 2012; McIntosh et al, 2017; Samboju, Philippi, Chan, Cobigo, Fletcher, Robb, Hellmuth, Benjapornpong, Dumrongpisutikul, Pothisri, Paul, Ananworanich, Spudich, Valcour, RV254, et al, 2018). The balanced integration of excitatory and inhibitory synaptic currents in the local cortex allows the cortical network to operate at high efficiency of information transmission at a low energy cost (Yu, Shen, Wang, & Yu, 2018).…”