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

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


Elisabet Ortiz-Tudela1, Antonio Martinez-Nicolas1, Manuel Campos2, María Ángeles Rol1*, Juan Antonio Madrid1

1 Chronobiology Laboratory, Department of Physiology, University of Murcia, Murcia, Spain, 2 Department of Computer Science and Systems, University of Murcia, Murcia, Spain

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.

Citation: Ortiz-Tudela E, Martinez-Nicolas A, Campos M, Rol MÁ, Madrid JA (2010) A New Integrated Variable Based on Thermometry, Actimetry and Body Position (TAP) to Evaluate Circadian System Status in Humans. PLoS Comput Biol 6(11): e1000996. doi:10.1371/journal.pcbi.1000996

Editor: Philip E. Bourne, University of California San Diego, United States of America

Received: April 20, 2010; Accepted: October 8, 2010; Published: November 11, 2010

Copyright: © 2010 Ortiz-Tudela et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors wish to thank the Instituto de Salud Carlos III, the Ministry of Education and Science and the Seneca Foundation for their financial support of this study through the Red de Investigacion Cooperativa en Envejecimiento y Fragilidad [The Ageing and Frailty Cooperative Research Network], RETICEF (RD06/0013/0019), BFU 2010-21945-CO1 to J. A. Madrid, and project 08853/PI/08 to M. Campos. Furthermore, the authors wish to thank the Ministry of Education and Science for the research fellowship awarded to E. Ortiz-Tudela (AP2008-2850) and to the University of Murcia for the research fellowship awarded to A. Martinez-Nicolas. Those funding this study played no role in the study design, data collection and analysis, the decision to publish or the preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: angerol@um.es

full-text:
PLoS Computational Biology: A New Integrated Variable Based on Thermometry, Actimetry and Body Position (TAP) to Evaluate Circadian System Status in Humans




NEUROLOGÍA
Actualidad Ultimas noticias - JANOes y agencias -
Investigadores españoles crean un índice para estudiar el ritmo de sueño y vigilia

JANO.es y agencias · 03 Enero 2011 09:40

Esta herramienta puede resultar útil para evaluar el sistema circadiano en pacientes con cáncer colorrectal, obesidad, apnea obstructiva del sueño e hipertensión arterial.


Investigadores del Laboratorio de Cronobiología de la Universidad de Murcia (UMU) han creado un Índice de Funcionamiento del Sistema Circadiano tras estudiar el registro ambulatorio de los ritmos circadianos humanos. Se trata de un avance de gran trascendencia en la clínica, ya que permite estudiar, entre otras cosas, el ritmo de sueño-vigilia sin utilizar polisomnografía.

El trabajo, publicado por la revista PLOS Computacional Biology, establece un abordaje metodológico que no se ha utilizado con anterioridad y que, junto con un nuevo índice denominado Circadian Function Index (CFI) o Índice de Funcionamiento del Sistema Circadiano, proporciona la herramienta que se necesita para evaluar y estandarizar el estado funcional del sistema circadiano.

El laboratorio murciano está utilizando estas herramientas en la clínica para la evaluación del sistema circadiano en relación con el envejecimiento, maduración de los ritmos circadianos en recién nacidos, en pacientes con cáncer colorrectal, obesidad, apnea obstructiva del sueño e hipertensión arterial.

Enfrentados a los ciclos ambientales y a la alternancia diaria entre la luz y la oscuridad, los organismos han desarrollado mecanismos para medir el tiempo, los relojes biológicos. Todas las variables fisiológicas muestran ritmos circadianos, pero además, esos ritmos deben estar coordinados entre sí, “como una orquesta bajo las órdenes de su director", explican los investigadores de la UMU.

Si no se lleva el ritmo apropiado "en vez de música se produce ruido y se pone en peligro la salud", y entre las afecciones más frecuentes producidas por estas alteraciones se encuentran el síndrome metabólico, la diabetes o enfermedades cardiovasculares, e incluso un peor pronóstico de enfermedades preexistentes como el cáncer.


PLoS Comput Biol 6(11): e1000996. doi:10.1371/journal.pcbi.1000996
PLoS Computational Biology: A New Integrated Variable Based on Thermometry, Actimetry and Body Position (TAP) to Evaluate Circadian System Status in Humans

Universidad de Murcia
Universidad de Murcia

Actualidad Ultimas noticias - JANOes y agencias - Investigadores espanoles crean un indice para estudiar el ritmo de sueno y vigilia - JANO.es - ELSEVIER