Brain structural changes associated with aberrant functional responses to the Valsalva maneuver in heart failure

Abstract

Heart failure (HF) patients show inability to regulate autonomic functions in response to autonomic challenges. The autonomic deficits may stem from brain tissue injury in central autonomic regulatory areas, resulting from ischemic and hypoxic processes accompanying the condition. However, the direct evaluation of correlations between brain structural injury and functional timing and magnitude of neural signal patterns within affected areas, which may lead to impaired autonomic outflow, is unclear. In this study, we evaluate neural responses to the Valsalva maneuver with blood oxygen level-dependent functional magnetic resonance imaging in 29 HF patients and 35 control subjects and brain structural changes using diffusion tensor imaging-based mean diffusivity in a subsample of 19 HF and 24 control subjects. HF showed decreased neural activation in multiple autonomic and motor control areas, including cerebellum cortices, vermis, left insular, left putamen, and bilateral postcentral gyrus. Structural brain changes emerged in similar autonomic, as well as cognitive and mood regulation areas. Functional MRI responses in cerebellum and insula in HF subjects are delayed or decreased in magnitude to the challenge. The impaired functional responses of insular and cerebellar sites are correlated with the severity of tissue changes. These results indicate that the functions of insular and cerebellar regions, sites that are involved in autonomic regulation, are compromised, and that autonomic deficits in these areas have brain structural basis for impaired functions. Our study enhanced our understanding of brain structural and functional alterations underlying impaired autonomic regulations in HF subjects.

How the insula speaks to the heart: Cardiac responses to insular stimulation in humans

“…In addition, our work reinforces some studies showing functional and structural alterations of the insula in cardiovascular diseases such as hypertension (Marins, Iddings, Fontes, & Filosa, ) or heart failure (Song, Roy, Fonarow, Woo, & Kumar, ). These insula alterations would maintain sympathetic hyperactivity and parasympathetic dysfunction, while it is well documented that these autonomic alterations predict morbidity and mortality in these populations (Malliani et al, ).…”

“…In particular, a neurovascular remodeling of the insular cortex was revealed in hypertension, which may contribute to the maintenance of sympathetic hyperactivity and of hypertension (Marins et al, ). In heart failure, Song et al () reported functional and structural alterations in the insula correlated with autonomic dysfunctions. Lastly, insular strokes have been associated with increased mortality (Laredo et al, ).…”

Aberrant left insular cortex response: A possible pathogenesis of reduced vagal nervous system activity in heart failure?

“…Thus, decreased left Ic response to the Valsalva maneuver reported by Song et al, (2018) was suggested to be associated with decreased parasympathetic nervous system activity in HF patients. Oppenheimer, Gelb, Girvin, and Hachinski (1992) have defined a site involved in cardiovascular regulation in the Ic.…”

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We have read the very interesting study by Song, Roy, Fonarow, Woo, and Kumar (2018) who showed that functional magnetic resonance imaging (MRI) responses of left insular cortex (Ic) in heart failure (HF) patients were delayed or decreased according to the magnitude of the Valsalva maneuver and that the impaired functional response of Ic had significant correlation with the degree of tissue changes.In earlier studies, the cardiovascular system has been suggested to be regulated by a central autonomic network (CAN) that consisted of the Ic, the anterior cingulate gyrus, and the amygdala (Nagai et al, 2017;Nagai, Hoshide, & Kario, 2010). In drug-refractory epilepsy patients, right hemispheric inactivation was associated with an increase in high frequency (HF) of the heart rate (HR) and blood pressure (BP), and the left hemispheric inactivation was associated with an increase in low frequency (LF) of HR and BP.

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“…We have read the very interesting study by Song, Roy, Fonarow, Woo, and Kumar (2018) who showed that functional magnetic resonance imaging (MRI) responses of left insular cortex (Ic) in heart failure (HF) patients were delayed or decreased according to the magnitude of the Valsalva maneuver and that the impaired functional response of Ic had significant correlation with the degree of tissue changes.…”