Dataset Information

From dawn to dusk-mimicking natural daylight exposure improves circadian rhythm entrainment in patients with severe brain injury.

ABSTRACT:

Study objectives

While light therapy has proven effective in re-entraining circadian rhythms, the potential of such an intervention has not been evaluated systematically in post-comatose patients with disorders of consciousness (DOC), who often have strongly altered circadian rhythms.

Methods

We recorded skin temperature over 7-8 days in patients with DOC in each of two conditions: habitual light (HL), and dynamic daylight (DDL) condition. While patients were in a room with usual clinic lighting in the HL condition, they were in an otherwise comparable room with biodynamic lighting (i.e. higher illuminance and dynamic changes in spectral characteristics during the day) in the DDL condition. To detect rhythmicity in the patients' temperature data, we computed Lomb-Scargle periodograms and analyzed normalized power, and peak period. Furthermore, we computed interdaily stability and intradaily variability, which provide information about rhythm entrainment and fragmentation.

Results

We analyzed data from 17 patients with DOC (i.e. unresponsive wakefulness syndrome [n = 15] and minimally conscious state [n = 2]). The period length of the patients' temperature rhythms was closer to 24 h in the DDL as compared to the HL condition (median median deviation from 24 h: DDL = 0.52 h, HL = 3.62 h). Specifically, in 11/17 (65%) patients the period length was closer to 24 h in the DDL condition. Furthermore, the patients' rhythm was more pronounced, more stable, and less variable in the DDL condition.

Conclusions

Our results indicate that DDL stimulation entrains and stabilizes circadian rhythms. This highlights the importance of adequate room lighting as an adjunct therapeutic approach for improving circadian rhythms in severely brain-injured patients.

Trial registration information

German Clinical Trials Register (DRKS00016041); registration: 18.01.2019; recording start: 04.06.2019 https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016041.

SUBMITTER: Angerer M

PROVIDER: S-EPMC9272242 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The circadian rhythm, called Process C, regulates a wide range of biological processes in humans including sleep, metabolism, body temperature, and hormone secretion. Light is the dominant synchronizer of the circadian rhythm-it has been used to regulate the circadian phase to cope with jet-lag, shift work, and sleep disorder. The homeostatic oscillation of the sleep drive is called Process S. Process C and Process S together determine the sleep-wake cycle in what is known as the two-process model. This paper addresses the regulation of both Process C and Process S by scheduling light exposure and sleep based on numerical simulations of circadian rhythm and sleep mathematical models. This is a significant step beyond the existing literature that only considers the entrainment of Process C. Regulation of the two-process model poses several unique features and challenges: 1. Process S is non-smooth, i.e., the homeostatic dynamics are different in the sleep and wake regimes; 2. Light only indirectly affects Process S through Process C; 3. Light does not affect Process C during sleep. We consider two scenarios: optimizing light intensity as the control input with spontaneous (i.e., unscheduled) sleep/wake times and jointly optimizing the light intensity and the sleep/wake times, which allows limited delayed sleep and early waking as part of the decision variables. We solve the time-optimal entrainment problem for the two-process model for both scenarios using an extension of the gradient descent algorithm to non-smooth systems. To illustrate the efficacy of our time-optimal entrainment strategies, we consider two common use cases: transmeridian travelers and shift workers. For transmeridian travelers, joint optimization of the two-process model avoids the unrealistic long wake duration when only Process C is considered. The entrainment time also decreases when both the light input and the sleep schedule are optimized compared to when only the light input is optimized. For shift workers, we show that the entrainment time is significantly shortened by optimizing the night shift working light.