There is large interindividual variability in circadian timing, which is underestimated by mathematical models of the circadian clock. Interindividual differences in timing have traditionally been modeled by changing the intrinsic circadian period, but recent findings reveal an additional potential source of variability: large interindividual differences in light sensitivity. Using an established model of the human circadian clock with real-world light recordings, we investigated whether changes in light sensitivity parameters or intrinsic circadian period could capture variability in circadian timing between and within individuals. Healthy participants (n = 12, aged 18-26 years) underwent continuous light monitoring for 3 weeks (Actiwatch Spectrum). Salivary dim-light melatonin onset (DLMO) was measured each week. Using the recorded light patterns, a sensitivity analysis for predicted DLMO times was performed, varying 3 model parameters within physiological ranges: (1) a parameter determining the steepness of the dose-response curve to light (p), (2) a parameter determining the shape of the phase-response curve to light (K), and (3) the intrinsic circadian period (tau). These parameters were then fitted to obtain optimal predictions of the three DLMO times for each individual. The sensitivity analysis showed that the range of variation in the average predicted DLMO times across participants was 0.65 h for p, 4.28 h for K, and 3.26 h for tau. The default model predicted the DLMO times with a mean absolute error of 1.02 h, whereas fitting all 3 parameters reduced the mean absolute error to 0.28 h. Fitting the parameters independently, we found mean absolute errors of 0.83 h for p, 0.53 h for K, and 0.42 h for tau. Fitting p and K together reduced the mean absolute error to 0.44 h. Light sensitivity parameters captured similar variability in phase compared with intrinsic circadian period, indicating they are viable targets for individualizing circadian phase predictions. Future prospective work is needed that uses measures of light sensitivity to validate this approach.

生物钟的数学模型低估了昼夜节律时间的个体间差异。时间上的个体差异传统上是通过改变内在昼夜节律来建模的，但最近的研究结果揭示了另一个潜在的变异来源：光敏感度的巨大个体差异。使用具有真实世界光记录的人类生物钟的既定模型，我们研究了光敏感参数或内在昼夜节律周期的变化是否可以捕获个体之间和个体内部昼夜节律时间的变化。健康参与者 ( n= 12，年龄 18-26 岁）接受了 3 周的连续光照监测（Actiwatch Spectrum）。每周测量唾液暗光褪黑激素起始 (DLMO)。使用记录的光模式，对预测的 DLMO 时间进行灵敏度分析，在生理范围内改变 3 个模型参数：(1) 确定剂量反应曲线对光 ( p )陡度的参数，(2) 确定参数对光的相位响应曲线的形状 ( K )，以及 (3) 内在昼夜节律 ( tau )。然后拟合这些参数以获得每个人的三个 DLMO 时间的最佳预测。敏感性分析表明，参与者平均预测 DLMO 时间的变化范围为 0.65 小时p，K为 4.28小时，tau为 3.26 小时。默认模型以 1.02 小时的平均绝对误差预测 DLMO 时间，而拟合所有 3 个参数将平均绝对误差降低到 0.28 小时。独立拟合参数，我们发现p 的平均绝对误差为 0.83 小时，K为0.53小时，tau为 0.42 小时。拟合p和K一起将平均绝对误差降低到 0.44 小时。与固有昼夜节律周期相比，光敏参数捕获了类似的相位变异性，表明它们是个性化昼夜节律相位预测的可行目标。未来的前瞻性工作需要使用光敏度的措施来验证这种方法。