Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli

Abstract

Ventromedial prefrontal cortex (VMPFC) lesions can alter emotional and autonomic responses. In animals, VMPFC activation results in cardiovascular sympathetic inhibition. In humans, VMPFC modulates emotional processing and autonomic response to arousal (e.g. accompanying decision-making). The specific role of the left or right VMPFC in mediating somatic responses to non-arousing, daily-life pleasant or unpleasant stimuli is unclear. To further evaluate VMPFC interaction with autonomic processing of non-stressful emotional stimuli and assess the effects of stimulus valence, we studied patients with unilateral VMPFC lesions and assessed autonomic modulation at rest and during physical challenge, and heart rate (HR) and blood pressure (BP) responses to non-stressful neutral, pleasant and unpleasant visual stimulation (VES) via emotionally laden slides. In 6 patients (54.0 +/- 7.2 years) with left-sided VMPFC lesions (VMPFC-L), 7 patients (43.3 +/- 11.6 years) with right-sided VMPFC lesions (VMPFC-R) and 13 healthy volunteers (44.7 +/- 11.6 years), we monitored HR as R-R interval (RRI), BP, respiration, end-tidal carbon dioxide levels, and oxygen saturation at rest, during autonomic challenge by metronomic breathing, a Valsalva manoeuvre and active standing, and in response to non-stressful pleasant, unpleasant and neutral VES. Pleasantness versus unpleasantness of slides was rated on a 7-point Likert scale. At rest, during physical autonomic challenge, and during neutral VES, parameters did not differ between the patient groups and volunteers. During VES, Likert scores also were similar across the three groups. During pleasant and unpleasant VES, HR decreased (i.e. RRI increased) significantly whereas BP remained unchanged in volunteers. In VMPFC-L patients, HR decrease was insignificant with pleasant and unpleasant VES. BP slightly increased (P = 0.06) with pleasant VES but was stable with unpleasant VES. In contrast, VMPFC-R patients had significant increases in HR and BP during pleasant and not quite significant HR increases (P = 0.06) with only slight BP increase during unpleasant VES. Other biosignals remained unchanged during VES in all groups. Our results show that VMPFC has no major influence on autonomic modulation at rest and during non-emotional, physical stimulation. The paradoxical HR and BP responses in VMPFC-R patients suggest hemispheric specialization for VMPFC interaction with predominant parasympathetic activation by the left, but sympathetic inhibition by the right VMPFC. Valence of non-stressful stimuli has a limited effect with more prominent left VMPFC modulation of pleasant and more right VMPFC modulation of unpleasant stimuli. The paradoxical sympathetic disinhibition in VMPFC-R patients may increase their risk of sympathetic hyperexcitability with negative consequences such as anxiety, hypertension or cardiac arrhythmias.

The Insular Cortex and the Regulation of Cardiac Function

“…In experiments investigating effects of positive or negative emotional stimuli on heart rate in those with a variety of lesions including head trauma, arteriovenous malformations, tumors, or stroke confined either to the right or left ventromedial prefrontal cortex (VMPFC) the results indicated that those with left sided lesions showed a blunted response (little heart rate change to emotional visual content compared to the decrease seen in controls) whereas those with right ventromedial prefrontal VMPFC cortical lesions had evidence of increased cardiovascular sympathetic responses (increased heart rate response compared to controls) (134). A rating scale indicated that the emotional content perceived by those in the three groups was similar.…”

Stroke-Induced Sudden-Autonomic Death

“…14 Left VMPFC lesions result in dampened heart rate or blood pressure adjustment to visual emotional stimuli, whereas right-sided VMPFC lesions bear a risk of exaggerated cardiovascular responses with paradoxical heart rate and blood pressure increase. 14 Similarly, lateralized effects on resting cardiovascular modulation have been observed after insular stroke. 11,[15][16][17] Zamrini et al 18 and Hilz et al 19 observed a hemispheric dominance of sympathetic or parasympathetic activity in temporal lobe epilepsy patients who underwent hemispheric inactivation during the so-called WADA testing procedure before epilepsy surgery.…”

“…An ischemiainduced decrease in sympathetic temporal lobe contribution to autonomic balance is likely to result in a shift toward cardiovagal predominance which then facilitates bradycardia or even asystole. 14,19 Surprisingly, Rincon and coworkers could not confirm a dominant association of the insular cortex with increased mortality. Some of the discrepancy to findings by Oppenheimer and coworkers 21 might be due to the fact that Oppenheimer deduced their conclusions from insular cortex stimulations in rodents, ie, from activation of brain areas that may be silent or dysfunctional after stroke.…”

Causal interactions between the cerebral cortex and the autonomic nervous system

“…The spectral power of the HRV was calculated in the low frequency (LF: 0.04-0.15 Hz) and high frequency (HF: 0.15-0.4 Hz) ranges [20,21]. The fluctuation of HR in the LF range is influenced by the baroreceptor system, and reflects both sympathetic and parasympathetic activity [22]. The fluctuation of HR in the HF range is mainly related to parasympathetic efferent activity.…”