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

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. While HF of HR or BP represents a parasympathetic nervous system activity, LF of HR or BP represents a sympathetic nervous system (SNS) activity (Hilz, et al., 2001). In addition, we recently observed that the case of herpes encephalitis with right Ic lesion had left ventricular (LV) dysfunction at one week after admission (Kikumoto et al., 2018). Cardiac 123I‐meta‐iodobenzylguanidine uptake scintigraphy revealed reduced regional LV uptake in the earlier phase. LV hypokinesis was suggested to be derived according to reduced SNS activity due to right Ic lesion (Kikumoto et al., 2018). Mishra, John, Shukla, Sathyaprabha, and Devi (2018) also suggested that suppressed left Ic activity due to gliomas allowed for decreased parasympathetic nervous system activity with relatively increased SNS tone. These results support the notion that the right Ic has an association with the SNS activity while the left Ic has an association with the parasympathetic nervous system activity. 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. Bradycardia or depressor effect was significantly more commonly observed after stimulation of the left Ic. The degree of bradycardia or depressor was significantly greater on the stimulation of the posterior portion than that of the anterior portion in the left Ic (Oppenheimer et al., 1992). Thus, the left posterior Ic is suggested to be strongly involved in the parasympathetic autonomic nervous system activity. Kitamura et al. (2018) showed that the damage of the left posterior Ic in acute ischemic stroke was associated with increased BP variability, which was one of the representative SNS markers. However, Song et al.,(2018) had no descriptions for the patterns of reduction in the left Ic responses to the Valsalva maneuver according to the anterior or posterior portion which was associated with the genesis of sympatho‐vagal imbalance. Until now, there have been no reports that assessed the relationship between left Ic activity and autonomic imbalance according to the anterior or posterior portion in patients with HF. The results of Song et al. (2018) would be of more importance in these study literatures if a clear mechanism underlying that relationship was presented.