Vulnerability to simple faints is predicted by regional differences in brain anatomy

Abstract

Neurocardiogenic syncope (NCS, simple fainting) is a common and typically benign familial condition, which rarely may result in traumatic injury or hypoxic convulsions. NCS is associated with emotional triggers, anxiety states and stress. However, the etiology of NCS, as a psychophysiological process, is poorly understood. We therefore investigated the relationship between NCS and brain anatomy. We studied a non-clinical sample of eighteen individuals with histories characteristic of NCS, and nineteen matched controls who had never fainted. We recorded fainting frequency, resting heart rate variability measures and anxiety levels. Structural T1-weighted magnetic resonance images (MRI) were acquired at 1.5 T. Associations between brain morphometry (regional gray and white matter volumes) and NCS, resting physiology and anxiety were tested using voxel-based morphometry (VBM). Compared to controls, NCS participants had lower regional brain volume within medulla and midbrain (a priori regions of interest). Moreover, across NCS individuals, lower gray matter volume in contiguous regions of left caudate nucleus predicted enhanced parasympathetic cardiac tone, fainting frequency and anxiety levels. Our findings provide preliminary evidence for a hierarchical anatomical basis to NCS. First, differences in the volume of brainstem centers supporting cardiovascular homeostasis may relate to constitutional predisposition to NCS. Second, differences in the structural organization of the caudate nucleus in NCS individuals may relate to fainting frequency via interactions between emotional state and parasympathetic control of the heart. These observations highlight the application of VBM to the identification of neurovisceral mechanisms relevant to psychosomatic medicine and the neuroscience of emotion.

Fig. 1

(A) Significant differences (two-tailed) in medullary gray matter volumes in individuals with a history of NCS (n = 18) and controls (n = 19), superimposed on T1-weighted images (medullary region centered at − 5, − 39, − 62). (B) Scatter plot of medullary gray matter for NCS and control groups, showing group means. (C) Significant differences (two-tailed) in midbrain white matter volumes in NCS individuals and controls. (D) Scatter plot of medullary gray matter for NCS and control groups, showing group means.

Fig. 2

(A) Left caudate region showing significant negative correlations between regional gray matter volumes and fainting frequency, within NCS participants. (B) Significant negative logarithmic relationship between HF-HRV and fainting frequency, within NCS participants [p = 0.005, R² = 0.422]. (C) Left caudate region showing significant negative correlations between regional gray matter volumes and HF-HRV, within NCS participants. Contrast estimates reveal this correlation was driven primarily by NCS participants.

Fig. 3

(A) caudate regions showing significant negative correlations between regional gray matter volumes and anxiety levels, within NCS participants. (B) Within NCS participants, left caudate regions showing significant negative correlations between regional gray matter volumes and anxiety levels (red), fainting frequency (yellow) and HF-HRV (green). These regions are also shown magnified and presented at p = 0.005.