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A generalized phase resetting method for phase-locked modes prediction.

ABSTRACT: We derived analytically and checked numerically a set of novel conditions for the existence and the stability of phase-locked modes in a biologically relevant master-slave neural network with a dynamic feedback loop. Since neural oscillators even in the three-neuron network investigated here receive multiple inputs per cycle, we generalized the concept of phase resetting to accommodate multiple inputs per cycle. We proved that the phase resetting produced by two or more stimuli per cycle can be recursively computed from the traditional, single stimulus, phase resetting. We applied the newly derived generalized phase resetting definition to predicting the relative phase and the stability of a phase-locked mode that was experimentally observed in this type of master-slave network with a dynamic loop network.

SUBMITTER: Oprisan SA

PROVIDER: S-EPMC5360347 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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A generalized phase resetting method for phase-locked modes prediction.

Oprisan Sorinel A SA Austin Dave I DI

PloS one 20170321 3

We derived analytically and checked numerically a set of novel conditions for the existence and the stability of phase-locked modes in a biologically relevant master-slave neural network with a dynamic feedback loop. Since neural oscillators even in the three-neuron network investigated here receive multiple inputs per cycle, we generalized the concept of phase resetting to accommodate multiple inputs per cycle. We proved that the phase resetting produced by two or more stimuli per cycle can be ...[more]

PMID: 28323894

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Project description:Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n = 16 males, mean age ± SD = 23.4 ± 2.3 years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near-identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n = 25, 14 females, 36.3 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue-enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue-enriched white light. In the delay protocols, the cholesterol rhythm shifted later by -3.7 hours and -4.2 hours, respectively, compared to -6.6 hours and -4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.

Project description:BACKGROUND. In humans, a single light exposure of 12 minutes and multiple-millisecond light exposures can shift the phase of the circadian pacemaker. We investigated the response of the human circadian pacemaker to a single 15-second or 2-minute light pulse administered during the biological night. METHODS. Twenty-six healthy individuals participated in a 9-day inpatient protocol that included assessment of dim light melatonin onset time (DLMO time) before and after exposure to a single 15-second (n = 8) or 2-minute (n = 12) pulse of bright light (9,500 lux; 4,100 K fluorescent) or control background dim light (<3 lux; n = 6). Phase shifts were calculated as the difference in clock time between the two phase estimates. RESULTS. Both 15-second and 2-minute exposures induced phase delay shifts [median (± SD)] of -34.8 ± 47.2 minutes and -45.4 ± 28.4 minutes, respectively, that were significantly (P = 0.04) greater than the control condition (advance shift: +22.3 ± 51.3 minutes) but were not significantly different from each other. Comparisons with historic data collected under the same conditions confirmed a nonlinear relationship between exposure duration and the magnitude of phase shift. CONCLUSIONS. Our results underscore the exquisite sensitivity of the human pacemaker to even short-duration single exposures to light. These findings may have real-world implications for circadian disruption induced by exposure to brief light stimuli at night. TRIAL REGISTRATION. The study was registered as a clinical trial on www.clinicaltrials.org, NCT #01330992. FUNDING. Funding for this study was provided by NSBRI HFP02802 and NIH P01-AG09975, R01-HL114088 (EBK), RC2-HL101340-0 (EBK, SWL, SAR, REK), K02-HD045459 (EBK), K24-HL105664 (EBK), T32-HL07901 (MSH, SAR), HL094654 (CAC), and AG044416 (JFD). The project described was supported by NIH grant 1UL1 TR001102-01, 8UL1TR000170-05, UL1 RR 025758, Harvard Clinical and Translational Science Center, from the National Center for Advancing Translational Science.

Dataset Information

A generalized phase resetting method for phase-locked modes prediction.

Publications

A generalized phase resetting method for phase-locked modes prediction.

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