Resetting Body Clock May Help the Brain to Heal

Circadian temperature rhythms linked to arousal in study

From MedPage Today | By Salynn Boyles

Circadian-related variations in body temperatures were found to be linked to arousal in people in vegetative or minimally conscious states in a newly reported study, suggesting a possible role for circadian rhythm manipulation in the treatment of severe brain injury.

Findings from the small, cross-sectional study provide early evidence for an association between circadian body temperature rhythms and arousal as a necessary precondition for consciousness, researcher Christine Blume, PhD, of Austria’s University of Saltzburg, and colleagues wrote.

Their study was published online April 19 in the journal Neurology.

The researchers wrote that temporal disorganization of circadian rhythms may impede recovery in critically ill patients, and that studying circadian rhythms in patients with consciousness disorders may be especially important for several reasons.

“First, the presence or absence of circadian rhythms as well as anomalies in them could be informative about the state of the patient as well as the potential for recovery,” they wrote. “Second, this could provide information about time points that best capture remaining cognitive functions, e.g., with behavioral scales such as the Coma Recovery Scale-Revised (CRS-R).”

Molecular biologist Helen Hellmich, PhD, of the University of Texas Medical Branch at Galveston, has been studying circadian rhythm disturbances in brain injured rats in her lab for almost two decades.

In an interview with MedPage Today, Hellmich said the newly published human study expands upon her work and those of her colleagues showing that brain injury disrupts circadian gene expression in rat models. They were the first to show this in a study and suggest a mechanism in a study published in the journal PLoS One in 2012.

She said ongoing studies by her colleagues suggest that bright light therapy speeds brain recovery among the brain injured rats, possibly by increasing levels of the protein brain derived neurotrophic factor, or BDNF.

In the newly published study, Blume and colleagues investigated circadian temperature rhythms under a habitual light condition for one week and they also explored the potential of bright light stimulation to enhance circadian rhythmicity.

Lomb-Scargle periodogram analyses revealed circadian rhythms in all 18 patients with period lengths ranging from 23.5 to 26.3 hours (median 23.95 hours). Patients with traumatic brain injury exhibited a marginally significantly longer period length than patients with nontraumatic cause.

Scores on the arousal subscale CRS-R were found to be closely linked to circadian variations in body temperature.

In a light-stimulation substudy, bright light stimulation appeared to boost circadian rhythmicity in two of the eight patients included in the substudy.

The intervention consisted of bright light stimulation three times a day (7 am, 1 pm and 7 pm) for one hour over the course of a week.

While there was some evidence of improvement in arousal in the two patients, the contribution of the light therapy was not clear and the effect was not statistically significant.

The researchers argued that a proof of principal study is needed "before drawing conclusions about the usefulness of bright light stimulation therapy.

In contrast to findings from smaller, similar studies published in 2009 and 2013, the current study showed circadian rhythms in all patients, regardless of disorder of consciousness state, which the researchers attributed to the increased sensitivity of their analysis methods.

“More precisely, our results indicate that the less the patients’ circadian temperature rhythm deviated from healthy rhythmicity,the better it was entrained to the 24-hour light-dark cycle and the more pronounced the circadian rhythm (i.e., the higher the normalized power of the circadian peak in the periodogram), the better the behavioral repertoire and the state of the patient (as measured with the CRS-R),” the researchers wrote.

This observation was especially pronounced for the arousal subscale.

Body temperature is believed to be a key player in the regulation of sleep-wake cycles and arousal levels, which are known to fluctuate in patients in vegetative, unresponsive wakefulness and minimally-conscious states, the researchers noted.

“Thus, preserved circadian temperature rhythms may stabilize the integrity of patients' sleep-wake patterns, which in turn would support sustained arousal and eventually attention and (residual) awareness,” they wrote. “From a clinical perspective, this renders circadian rhythms promising targets for therapeutic approaches and our findings therefore make a case for treatment aiming at the promotion and stabilization of circadian rhythms.”

“There is a whole lot going wrong with the brain in people with severe brain injuries,” Hellmich said. “Circadian disruptions is just one thing, but it may be a very important thing.”

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