Altered Relationship Between Heart Rate Variability and fMRI-Based Functional Connectivity in People With Epilepsy

Abstract

Background: Disruptions in central autonomic processes in people with epilepsy have been studied through evaluation of heart rate variability (HRV). Decreased HRV appears in epilepsy compared to healthy controls, suggesting a shift in autonomic balance toward sympathetic dominance; recent studies have associated HRV changes with seizure severity and outcome of interventions. However, the processes underlying these autonomic changes remain unclear. We examined the nature of these changes by assessing alterations in whole-brain functional connectivity, and relating those alterations to HRV.Methods: We examined regional brain activity and functional organization in 28 drug-resistant epilepsy patients and 16 healthy controls using resting-state functional magnetic resonance imaging (fMRI). We employed an HRV state-dependent functional connectivity (FC) framework with low and high HRV states derived from the following four cardiac-related variables: 1. RR interval, 2. root mean square of successive differences (RMSSD), 4. low-frequency HRV (0.04–0.15 Hz; LF-HRV) and high-frequency HRV (0.15–0.40 Hz; HF-HRV). The effect of group (epilepsy vs. controls), HRV state (low vs. high) and the interactions of group and state were assessed using a mixed analysis of variance (ANOVA). We assessed FC within and between 7 large-scale functional networks consisting of cortical regions and 4 subcortical networks, the amygdala, hippocampus, basal ganglia and thalamus networks.Results: Consistent with previous studies, decreased RR interval (increased heart rate) and decreased HF-HRV appeared in people with epilepsy compared to healthy controls. For both groups, fluctuations in heart rate were positively correlated with BOLD activity in bilateral thalamus and regions of the cerebellum, and negatively correlated with BOLD activity in the insula, putamen, superior temporal gyrus and inferior frontal gyrus. Connectivity strength in patients between right thalamus and ventral attention network (mainly insula) increased in the high LF-HRV state compared to low LF-HRV; the opposite trend appeared in healthy controls. A similar pattern emerged for connectivity between the thalamus and basal ganglia.Conclusion: The findings suggest that resting connectivity patterns between the thalamus and other structures underlying HRV expression are modified in people with drug-resistant epilepsy compared to healthy controls.

Disrupted Brain Functional Status in Patients with Reversible Cerebral Vasoconstriction Syndrome

“…These phenomena were consistent with our previous study using HRV as a surrogate of systemic autonomic function, in which we demonstrated parasympathetic hypofunction in RCVS patients in the acute stage with partial improvement in the remission stage 12 . Corroborated with our findings, previous studies also reported that the insular dysfunctions may result in significant change of HRV 38,39 . Insular lateralization may have differential cardiac effects, and the left insula is particularly related to parasympathetic control 40,41 .…”

“…12 Corroborated with our findings, previous studies also reported that the insular dysfunctions may result in significant change of HRV. 38,39 Insular lateralization may have differential cardiac effects, and the left insula is particularly related to parasympathetic control. 40,41 Some studies have demonstrated potential connections of left insular damage to specific cardiac disorders with parasympathetic dysfunctions, including Takotsubo cardiomyopathy, 42,43 which is a cardiac disease that potentially shares characteristics with RCVS.…”

Altered spontaneous brain activity during dobutamine challenge in healthy young adults: A resting-state functional magnetic resonance imaging study

“…The elevated heart rate but reduced functional activity in the corresponding regions in the present study is also consistent with the results of a study linking regional BOLD fluctuations to heart rate, in that a negative correlation occurred between the bilateral orbitofrontal cortex and heart rate (Kassinopoulos et al, 2021).…”

Does global signal regression alter fMRI connectivity patterns related to EEG activity? An EEG-fMRI study in humans

“…Even in the absence of overt behaviour, brain activity fluctuates in an organized fashion in the form of large-scale brain networks that resemble those observed during behavioral tasks (Biswal et al, 1995; Fox and Raichle, 2007; Gratton et al, 2018; Smith et al, 2009). Functional magnetic resonance imaging (fMRI) has been widely used for studying the resting-state activity of temporally correlated and spatially distributed brain regions, and has shown promise to uncover mechanisms underlying neurological disorders (Gratton et al, 2019; Kassinopoulos et al, 2021; Xia et al, 2018). However, the blood-oxygenated level dependent (BOLD) signal typically employed in fMRI studies is only partially attributed to neural activity.…”