Brain metabolites in autonomic regulatory insular sites in heart failure

Abstract

Autonomic, pain, and neuropsychologic comorbidities appear in heart failure (HF), likely resulting from brain changes, indicated as loss of structural integrity and functional deficits. Among affected brain sites, the anterior insulae are prominent in serving major regulatory roles in many of the disrupted functions commonly seen in HF. Metabolite levels, including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and myo-inositol (MI), could indicate the nature of anterior insula tissue injury in HF. The study aim was to assess anterior insular metabolites to determine processes mediating autonomic, pain, and neuropsychologic disruptions in HF. We performed magnetic resonance spectroscopy in bilateral anterior insulae in 11 HF and 53 controls, using a 3.0-Tesla magnetic resonance imaging scanner. Peaks for NAA at 2.02ppm, Cr at 3.02ppm, Cho at 3.2ppm, and MI at 3.56ppm were assigned, peak areas calculated, and metabolites expressed as ratios, including NAA/Cr, Cho/Cr, and MI/Cr. HF patients showed significantly increased Cho/Cr ratios, indicative of glial proliferation or injury, on the left anterior insula, and reduced NAA/Cr levels, suggesting neuronal loss/dysfunction, on the right anterior insula over controls. No differences in MI/Cr ratios appeared between groups. Right anterior insular neuronal loss and left glial alterations may contribute to distorted autonomic, pain, and neuropsychologic functions found in HF.

Heart and brain interaction in patients with heart failure: overview and proposal for a taxonomy. A position paper from the Study Group on Heart and Brain Interaction of the Heart Failure Association

“…This has implications for our assessment of chronic actions of the chemoreflex, baroreflex, and central sympatho–vagal balance. Imaging studies of brain areas involved in autonomic regulation have shown distinct metabolic alterations and abnormal functional response to autonomic challenges such as Valsalva manoeuvre or cold pressure challenges . Abnormal blood pressure, heart rate and breathing control, which derives from a reduction in baroreflex sensitivity and a concomitant increase in both peripheral and central chemosensitivity, leads to a classical pattern on reflex instability with a reduction in high and low frequency oscillations and a dominant very low frequency oscillation, which in many cases (both in sleep and wakefulness) can manifest as frank Cheyne–Stokes respiration.…”

Forebrain neurocircuitry associated with human reflex cardiovascular control

“…Longer-term disruption of cardiovascular regulation can be observed as well, as indicated by Critchley et al ( 2003 ) who reported reduced cardiovascular arousal in three patients following stroke isolated to the anterior cingulate cortex (ACC). In addition to acute cortical damage models, the observations of significant changes in structure, function and metabolite levels of the insula in patients with heart failure (Woo et al, 2003 , 2014 ) and obstructive sleep apnea (Macey et al, 2008 ; Fatouleh et al, 2014 ; Yadav et al, 2014 ) highlight the growing understanding that cortical autonomic regions have broad-based involvement in cardiovascular disease.…”

The Neuroprotective Effects of Endurance Training on the Aging Brain

“…The insula cortex (IC) exhibits strong associations with cardiovascular control in functional imaging studies with humans (Cechetto and Saper 1990, Kimmerly, O'Leary et al 2005, Macey, Wu et al 2012, clinical studies (Critchley, Mathias et al 2003, Woo, Macey et al 2003, Woo, Yadav et al 2014, and experimental rodent models (Cechetto andChen 1990, Verberne and. These associations are representative of strong sensory, as well as efferent top-down, sensitivities of this region.…”

“…Experimental models in rodents , as well as clinical , Critchley, Mathias et al 2003, Woo, Macey et al 2003, Woo, Yadav et al 2014, and observational studies in humans , indicate that several cortical sites modulate autonomic cardiovascular control. In fact, cognitive (Critchley, Mathias et al 2003, Critchley, Wiens et al 2004, Critchley, Rotshtein et al 2005, Critchley, Nagai et al 2011) and autonomic network regions (Cechetto and appear to overlap in critical cortical sites including the medial prefrontal cortex (MPFC), hippocampus (HC), anterior cingulate cortex (ACC), and insula cortex (IC) , Soufer, Bremner et al 1998, Gianaros, Derbyshire et al 2005.…”

“…Certainly, experimental models in lower animals , as well as clinical , Critchley, Mathias et al 2003, Woo, Macey et al 2003, Woo, Yadav et al 2014, and observational studies in humans ) , indicate that several cortical sites modulate autonomic cardiovascular control.…”