A New Integrated Variable Based on Thermometry, Actimetry and Body Position (TAP) to Evaluate Circadian System Status in Humans

Abstract

The disruption of the circadian system in humans has been associated with the development of chronic illnesses and the worsening of pre-existing pathologies. Therefore, the assessment of human circadian system function under free living conditions using non-invasive techniques needs further research. Traditionally, overt rhythms such as activity and body temperature have been analyzed separately; however, a comprehensive index could reduce individual recording artifacts. Thus, a new variable (TAP), based on the integrated analysis of three simultaneous recordings: skin wrist temperature (T), motor activity (A) and body position (P) has been developed. Furthermore, we also tested the reliability of a single numerical index, the Circadian Function Index (CFI), to determine the circadian robustness. An actimeter and a temperature sensor were placed on the arm and wrist of the non-dominant hand, respectively, of 49 healthy young volunteers for a period of one week. T, A and P values were normalized for each subject. A non-parametric analysis was applied to both TAP and the separate variables to calculate their interdaily stability, intradaily variability and relative amplitude, and these values were then used for the CFI calculation. Modeling analyses were performed in order to determine TAP and CFI reliability. Each variable (T, A, P or TAP) was independently correlated with rest-activity logs kept by the volunteers. The highest correlation (r = −0.993, p<0.0001), along with highest specificity (0.870), sensitivity (0.740) and accuracy (0.904), were obtained when rest-activity records were compared to TAP. Furthermore, the CFI proved to be very sensitive to changes in circadian robustness. Our results demonstrate that the integrated TAP variable and the CFI calculation are powerful methods to assess circadian system status, improving sensitivity, specificity and accuracy in differentiating activity from rest over the analysis of wrist temperature, body position or activity alone.

Author Summary

Faced with environmental cycles and daily alternation between light and darkness, organisms have evolved a time measuring mechanism, the biological clocks. Besides following circadian rhythms, all physiological variables must be coordinated with one another, like an orchestra led by a conductor; if the appropriate rhythm is not kept, noise rather than music is produced. In an organism, when this temporal order is disrupted due to aging or shift work, health is compromised. Afflictions include metabolic syndrome, diabetes and cardiovascular diseases, among others, or even worse prognosis of preexisting illnesses like cancer. Since the circadian pacemaker (suprachiasmatic nuclei) is located deep within the brain in humans, the only way to evaluate its function is by assessing the output signals, observing marker rhythms such as the sleep-wake cycle, body temperature or activity. The problem is that isolated variable measurement is not error free. However, we can increase reliability by combining the information from several circadian marker rhythms in an integrated variable that we have called TAP (Temperature, Activity and Position), a methodological approach that has not been used before, that in conjunction with a new index called Circadian Function Index, provides a useful tool for standardizing the status of the circadian system.