fMRI Revealed Reduced Amygdala Activation after Nx4 in Mildly to Moderately Stressed Healthy Volunteers in a Randomized, Placebo-Controlled, Cross-Over Trial

Abstract

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 .

EEG revealed improved vigilance regulation after stress exposure under Nx4 – A randomized, placebo-controlled, double-blind, cross-over trial

“…It is approved by the German Federal Institute for Drugs and Medical Devices (German: Bundesinstitut für Arzneimittel und Medizinprodukte [BfArM]) for the treatment of sleep disorders and restlessness. Its effects have been demonstrated in several human ( Doering et al, 2016 , Herrmann et al, 2020 , Hübner et al, 2009H , Waldschütz and Klein, 2008 ) and rodent studies ( Dimpfel, et al, 2012 ). Thus, the intake of Nx4 for 28 days was shown to improve sleep quality by increasing sleep duration and reducing sleep latency as reported in patients’ sleep diaries over 14 days, and at the end of the study ( Waldschütz and Klein, 2008 ).…”

Amygdala Changes Through Breathing Exercise in Coping with the COVID-19 Pandemic

“…Noradrenaline is increased during the stress period. This will sensitize the amygdala (Herrmann et al, 2020).…”

“…It means there are lateralization effects of the amygdala when there is any stressor. The left amygdala has more frequent activation compared to the right one in trauma conditions such as post-traumatic stress disorders (Herrmann et al, 2020).…”

“…It is sensitized by acute stress. Acute stress will cause anxiety (Herrmann et al, 2020). However, the change of the amygdala is dynamic.…”

Cracking the Snake Detection Theory: The Subcortical Visual Pathway as a Major Player in Cultural Transformations

“…Perhaps the bilateral activation of the amygdala stands for an interhemispheric information transfer [79]. It seems there is a preference in the left section for images that evoke reasons for fear, as scared faces are surely bound to [80] [81]. Also, the left amygdala, as opposed to the right one, seem to be, according to a lesion study, important for the emotional enhancement of some stimuli, including aversive ones [81].…”