Intensification of functional neural control on heartbeat dynamics in subclinical depression

Abstract

Subclinical depression (dysphoria) is a common condition that may increase the risk of major depression and leads to impaired quality of life and severe comorbid somatic diseases. Despite its prevalence, specific biological markers are unknown; consequently, the identification of dysphoria currently relies exclusively on subjective clinical scores and structured interviews. Based on recent neurocardiology studies that link brain and cardiovascular disorders, it was hypothesized that multi-system biomarkers of brain-body interplay may effectively characterize dysphoria. Thus, an ad hoc computational technique was developed to quantify the functional bidirectional brain-heart interplay. Accordingly, 32-channel electroencephalographic and heart rate variability series were obtained from 24 young dysphoric adults and 36 healthy controls. All participants were females of a similar age, and results were obtained during a 5-min resting state. The experimental results suggest that a specific feature of dysphoria is linked to an augmented functional central-autonomic control to the heart, which originates from central, frontopolar, and occipital oscillations and acts through cardiovascular sympathovagal activity. These results enable further development of a large set of novel biomarkers for mood disorders based on comprehensive brain-body measurements.

Fig. 1. CAN scheme.

Schematic diagram showing the major central pathways regulating cardiac sympathetic (red) and parasympathetic (blue) outflows. Common pathways are indicated in purple. No distinction is made between the excitatory and inhibitory connections. DMNX dorsal motor nucleus of the vagus nerve, l lateral, MDH medullary dorsal horn of the trigeminal nucleus, MPFC medial prefrontal cortex, NAmb nucleus ambigus, NTS nucleus of the tractus solitarius, PAG periaqueductal grey matter, PVN hypothalamic paraventricular nucleus, vl ventrolateral, CVLM caudal ventrolateral medulla, DMH dorsomedial hypothalamus, RVLM rostral ventrolateral medulla, RVMM rostral ventromedial medulla (for more abbreviations, refer to text).

Fig. 2. Topographic distribution of the extracted BHI indexes in healthy participants during a resting state.

BHI indexed are explained in Table 2. (arbitrary units).

Fig. 3. Topographic distribution of the extracted BHI indexes in participants with dysphoria during a resting state.

BHI indexes are explained in Table 2. (arbitrary units).

Fig. 4. P-value topographic maps from non-parametric Mann–Whitney tests for unpaired samples in the proposed brain–heart model, between healthy subjects and dysphoric ones, in a resting state.

Significant brain regions (p < 0.05, corrected through multiple comparisons) are highlighted with respect to the green areas, which indicate no significant changes between conditions. Blue regions represent a BHI that is significantly higher in dysphoric subjects.

Fig. 5

Topographic distribution of the extracted HEP indexes in healthy (left) and dysphoric (right) participants during 5 min in a resting state.