The brain continuously receives input from the internal and external environment. Using this information, the brain exerts its influence on both itself and the body to facilitate an appropriate response. The dynamic interplay between the brain and the heart and how external conditions modulate this relationship deserves attention. In high-stress situations, synchrony between various brain regions such as the prefrontal cortex and the heart may alter. This flexibility is believed to facilitate transitions between functional states related to cognitive, emotional, and especially autonomic activity. This study examined the dynamic temporal functional association of heart rate variability (HRV) with the interaction between three main canonical brain networks in 38 healthy male subjects at rest and directly after a psychosocial stress task. A sliding window approach was used to estimate the functional connectivity (FC) among the salience network (SN), central executive network (CEN), and default mode network (DMN) in 60-s windows on time series of blood-oxygen-level dependent (BOLD) signal. FC between brain networks was calculated by Pearson correlation. A multilevel linear mixed model was conducted to examine the window-by-window association between the root mean square of successive differences between normal heartbeats (RMSSD) and FC of network-pairs across sessions. Our findings showed that the minute-by-minute correlation between the FC and RMSSD was significantly stronger between DMN and CEN than for SN and CEN in the baseline session [b = 4.36, t(5025) = 3.20, p = 0.006]. Additionally, this differential relationship between network pairs and RMSSD disappeared after the stress task; FC between DMN and CEN showed a weaker correlation with RMSSD in comparison to baseline [b = −3.35, t(5025) = −3.47, p = 0.006]. These results suggest a dynamic functional interplay between HRV and the functional association between brain networks that varies depending on the needs created by changing conditions.

Social stress contributes to major societal health burdens, such as anxiety disorders and nervousness. Nx4 has been found to modulate stress responses. We investigated whether dampening of such responses is associated with neuronal correlates in brain regions involved in stress and anxiety. In a randomized, placebo-controlled, double-blind, cross-over trial, 39 healthy males took a single dose (three tablets) of either placebo or Nx4, 40 to 60 minutes before an fMRI scan session. We here report on drug effects on amygdala responses during a face-matching task, which was performed during a complex test battery further including resting-state brain connectivity and a social stress experiment. The first of the Primary Outcomes, defined in a hierarchical order, concerned reduced amygdala effects after intake of verum compared to placebo. We found a statistically significant reduction in differential activations in the left amygdala for the contrast negative faces versus forms during verum versus placebo condition. Our results indicate that effects of Nx4 can be monitored in the brain. Previously noted effects on stress responses may thus be modulated by affective brain regions including the amygdala. More than half of the population in Germany suffered from stress in the past five years, and almost 25% suffered frequently 1. But what is stress? Hans Selye influenced the definition of the term "stress", describing it as "the non-specific response of the body to any demand for change" 2. The reaction of the body to any unexpected positive or negative stimuli from external and internal cues for survival was defined to be stress. Nowadays, the term "stress" usually refers to a state of tension. Depending on the cognitive appraisal of the physiological outcome and the stress-inducing stimulus, a highly recurrent and long-lasting tension state may lead to a maladaptive reaction to the stressor and an increase in physio-and psychopathology 3-5. Chronic stress is assumed to be a major risk factor for several physical and psychological disorders leading to increased heart rate and blood pressure, raised cholesterol, headache, restlessness, inability to concentrate, fatigue, state of anxiety, and feeling of depression 6 .

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