Feeling faint? AI’s got your back

Scientists have finally figured out the neural mechanisms that cause us to faint, offering a promising avenue of research for treating fainting-associated conditions.

Around 40% of individuals report at least one episode of syncope, or fainting, during their lifetime. In fact, losing consciousness is accountable for approximately 3% of emergency room visits and 6% of hospital admissions every year.

Despite being incredibly common, we have struggled to deduce the neural mechanisms behind what causes us to blackout. We understand what can trigger such events, such as dehydration, a sudden drop in blood pressure, or intense distress, but the root neuronal activity has remained elusive. Until now…

A collaborative effort from researchers from The Scripps Research Institute (CA, USA), University of California San Diego (USA) and other institutions has pinpointed the neurons responsible for inducing syncope, for the first time ever identifying the neural connections between the heart and brain.

To unearth this discovery, the team set about investigating the mechanisms involved in Bezold-Jarisch reflex (BJR), a cardioinhibitory reflex that is characterized by a triad of responses: bradycardia (abnormally low resting heart rate), hypotension (abnormally low blood pressure) and hypopnea (abnormally slow breathing). BJR has long been suspected to be mediated by vagal sensory neurons (VSNs), which are also thought to be linked to syncope.

Using single-cell RNA-sequencing data and HYBRiD tissue clearing, the team demonstrated that VSNs expressing neuropeptide Y receptor Y2 (NPY2R) primarily connect the ventricular wall of the heart to the area postrema, a structure in the brain stem with a vital role in controlling involuntary physiologic processes such as blood pressure and heart rate. When the team stimulated these NPY2R VSNs in mice using optogenetic activation, the BJR was elicited and the mice immediately fainted. During stimulation of the mice, the team recorded a variety of data, including heart activity, pupil diameter and whisking.

This data was analyzed using machine learning modelling, which illustrated that the activation of NPY2R VSNs suppressed blood flow to the brain, heart rate, blood pressure and breathing in mice. In additional testing, the team discovered that removing NPY2R VSNs in mice eliminated the BJR.

Vineet Augustine, School of Biological Sciences Assistant Professor at the University of California San Diego, stated, “what we are finding is that the heart also sends signals back to the brain, which can change brain function. Information resulting from the study could be relevant to better understanding and treating various psychiatric and neurological disorders linked with brain-heart connections, the researchers note in their paper.”

“Our study is the first comprehensive demonstration of a genetically defined cardiac reflex, which faithfully recapitulates characteristics of human syncope at physiological, behavioral and neural network levels.”

This research fundamentally changes the way we view the brain. Our traditional assumptions are that the brain controls our body through constant signaling, but it is now clear that the body also sends signals to the brain which then alters its function in response.

In the future, the team plans to undertake further research to better understand the causes of fainting, as well as develop targeted treatments for fainting-associated conditions.