Researchers at UCLA’s Department of Neurology and Drug Discovery Lab have identified a novel set of biomarkers that change based on levels of Cognitive Fatigue (CF). These biomarkers can be used to non-invasively predict and assess levels of cognitive fatigue.
BACKGROUND: Cognitive fatigue (CF) is an important factor in the efficiency and safety of performance-dependent tasks. CF-associated changes in overall physical state, reflect alterations in both cell signaling processes and biochemistry. It is postulated that the degree of CF experienced by an individual may be reflected by biomarkers in biofluids, such as saliva. Neuronal innervation of the salivary gland results in secretion of neuron-derived exosomes into saliva, while harboring signal molecules (proteins, lipids, mRNA, miRNA, DNA) that are indicative of changes in the cellular and molecular landscape of the central nervous system.
Understanding and accurately assessing CF levels is of great interest to a variety of sectors where operators are tasked with high-risk or high-cognitive load tasks requiring the user to execute with minimal mistakes. These sectors include but are not limited to the military, medicine, aviation, and finance. However, quantifying levels of CF is difficult and typical cognitive tests may be misleading as they can be memorized and habituated, in addition to taking valuable time to perform. As a result, there is a need for non-invasive methods of quantifying cognitive fatigue, and which can’t be altered by the user or biased by the administrator.
INNOVATION: UCLA researchers in the departments of Neurology and the Drug Discovery Lab have elucidated protein and microRNA biomarkers that vary significantly with CF in salivary neuronal exosomes. With these findings, they developed a novel panel of biomarkers for non-invasively assessing levels of CF. The biomarker panel was created and optimized on brain-derived exosomes which appear on saliva because of various brain-connected nerves and tissue layers innervating the salivary gland. These biomarkers rely on exosomes, small membrane-bound vesicles which can be readily found in the saliva.
This is the first discovery of a catalog of molecular predictors of cognitive fatigue present in saliva exosomes. The inclusion of various both miRNA and proteins in this panel, allows for two different approaches to assessing CF. Additionally, the panel contains markers that move in both directions, increasing or decreasing as CF goes up. By assessing CF on multiple fronts, miRNA, protein, increase/decrease, this panel provides a wholistic assessment of CF that is quantifiable and limitedly biased by user physiology. These biomarkers can be utilized in various situations to de-risk operators/user performance before performing high-risk or high-cognitive load tasks. Understanding these changes will enable development of training programs that enhance pilot cognitive endurance.
POTENTIAL APPLICATIONS:
- Detecting Cognitive Fatigue (CF) as a result of a particular event
- Assessing CF as a basis of time
- Assessing CF of operators in high-risk positions (e.g. fighter pilots, surgeons, patients)
- Aid in the development of cockpit devices and training programs to reduce CF in high-cognitive load tasks
ADVANTAGES:
- Non-invasive
- Relies on brain-derived exosomes
- Panel of various biomarkers
DEVELOPMENT-TO-DATE: The project was initiated in September 2017 funded by a grant from the US Air Force. A panel of biomarkers has been developed based on a cohort which underwent a 12-hour cognitively fatiguing event. Publication in an academic journal was successful in 2022.
Related Papers (from the inventors only): Cohn, W., Zhu, C., Campagna, J., Bilousova, T., Spilman, P., Teter, B., ... & John, V. (2022). Integrated Multiomics Analysis of Salivary Exosomes to Identify Biomarkers Associated with Changes in Mood States and Fatigue. Int. J. Mol. Sci., 23(9), 5257; doi.org/10.3390/ijms23095257