Brain correlates of autonomic modulation: Combining heart rate variability with fMRI

Abstract

The central autonomic network (CAN) has been described in animal models but has been difficult to elucidate in humans. Potential confounds include physiological noise artifacts affecting brainstem neuroimaging data, and difficulty in deriving non-invasive continuous assessments of autonomic modulation. We have developed and implemented a new method which relates cardiac-gated fMRI timeseries with continuous-time heart rate variability (HRV) to estimate central autonomic processing. As many autonomic structures of interest are in brain regions strongly affected by cardiogenic pulsatility, we chose to cardiac-gate our fMRI acquisition to increase sensitivity. Cardiac-gating introduces T1-variability, which was corrected by transforming fMRI data to a fixed TR using a previously published method (Guimaraes et al. 1998). The electrocardiogram was analyzed with a novel point process adaptive-filter algorithm for computation of the high-frequency (HF) index, reflecting the time-varying dynamics of efferent cardiovagal modulation. Central command of cardiovagal outflow was inferred by using the HF timeseries resampled at as a regressor to the fMRI data. A grip task was used to perturb the autonomic nervous system. Our combined HRV-fMRI approach demonstrated HF correlation with fMRI activity in the hypothalamus, cerebellum, parabrachial nucleus/locus ceruleus, periaqueductal gray, amygdala, hippocampus, thalamus, and dorsomedial/dorsolateral prefrontal, posterior insular, and middle temporal cortices. While some regions consistent with central cardiovagal control in animal models gave corroborative evidence for our methodology, other mostly higher cortical or limbic-related brain regions may be unique to humans. Our approach should be optimized and applied to study the human brain correlates of autonomic modulation for various stimuli in both physiological and pathological states.

Neurobiological substrates of cognitive rigidity and autonomic inflexibility in generalized anxiety disorder

“…The cerebellum is certainly involved in physiological regulation as a component of the central autonomic network (Spyer, 1999) contributing to the control of cardiovascular responses through its connections with the hypothalamus (Critchley, Corfield, Chandler, Mathias, & Dolan, 2000). Accordingly, covariation is observed between HRV and the cerebellum (Critchley et al 2003;Gianaros, Van Der Veen, & Jennings, 2004;Lane et al, 2009;Napadow et al, 2008).…”

Autonomic dysfunction in multiple sclerosis presenting with postural orthostatic tachycardia

“…Tachycardic response is mediated via sympathetic outflow from the rostral ventrolateral medulla that is modulated by excitatory and inhibitory, more central inputs [5]. Specifically, a positive correlation was found in the left hypothalamus, left amygdala, right anterior hippocampus, and right dorsomedial and dorsolateral prefrontal cortex, while a negative correlation was found in the right parabrachial nucleus/locus ceruleus, left periqueductal gray matter, right posterior hippocampus, right mediodorsal thalamus, left caudate and right septal nuclei, left posterior insula, and right medial temporal gyrus [6]. Therefore the probable mechanism of postural orthostatic tachycardia in our patient is thalamic lesion, which by inhibition of negative effect of right mediodorsal thalamic nucleus on heart rare could produce tachycardia.…”

Measurement fidelity of heart rate variability signal processing: The devil is in the details

“…There is growing interest and advancements using neuroimaging techniques (e.g., functional magnetic resonance imaging) to better understand neurobiological (brain-body) interactions (c.f., Gianaros and Sheu, 2009;Gianaros et al, 2004). For example, HF has been associated with activity within the ventral anterior cingulate (Matthews et al, 2004), posterior cingulate cortex (O'Connor et al, 2007), amygdala, periaqueductal gray, and the hypothalamus in response to somatosensory stimuli (Gray et al, 2009) and isometric exercise (Napadow et al, 2008). Given the evidence of an association between the brain and the ANS (i.e., parasympathetic and sympathetic activity), these promising research directions underscore the importance of purposeful and informed selection of HRV parameters.…”