In mammals, the pupillary light reflex is mediated by intrinsically photosensitive melanopsin-containing retinal ganglion cells that also receive input from rod-cone photoreceptors. To assess the relative contribution of melanopsin and rod-cone photoreceptors to the pupillary light reflex in humans, we compared pupillary light responses in normally-sighted individuals (n = 24) with a blind individual lacking rod-cone function. Here, we show that visual photoreceptors are required for normal pupillary responses to continuous light exposure at low irradiance levels, and for sustained pupillary constriction during exposure to light in the long-wavelength portion of the visual spectrum. In the absence of rod-cone function, pupillomotor responses are slow and sustained, and cannot track intermittent light stimuli, suggesting that rods/cones are required for encoding fast modulations in light intensity. In sighted individuals, pupillary constriction decreased monotonically for at least 30 minutes during exposure to continuous low-irradiance light, indicating that steady-state pupillary responses are an order of magnitude slower than previously reported. Exposure to low-irradiance intermittent green light (543 nm; 0.1–4 Hz) for 30 min, which was given to activate cone photoreceptors repeatedly, elicited sustained pupillary constriction responses that were more than twice as great compared to exposure to continuous green light. Our findings demonstrate non-redundant roles for rod-cone photoreceptors and melanopsin in mediating pupillary responses to continuous light. Moreover, our results suggest that it might be possible to enhance non-visual light responses to low-irradiance exposures by using intermittent light to activate cone photoreceptors repeatedly in humans.

The circadian system regulates daily rhythms in lipid metabolism and adipose tissue function. Although disruption of circadian clock function is associated with negative cardiometabolic end points, very little is known about interindividual variation in circadianregulated metabolic pathways. Here, we used targeted lipidomicsbased approaches to profile the time course of 263 lipids in blood plasma in 20 healthy individuals. Over a span of 28 h, blood was collected every 4 h and plasma lipids were analyzed by HPLC/MS. Across subjects, about 13% of lipid metabolites showed circadian variation. Rhythmicity spanned all metabolite classes examined, suggesting widespread circadian control of lipid-mediated energy storage, transport, and signaling. Intersubject agreement for lipids identified as rhythmic was only about 20%, however, and the timing of lipid rhythms ranged up to 12 h apart between individuals. Healthy subjects therefore showed substantial variation in the timing and strength of rhythms across different lipid species. Strong interindividual differences were also observed for rhythms of blood glucose and insulin, but not cortisol. Using consensus clustering with iterative feature selection, subjects clustered into different groups based on strength of rhythmicity for a subset of triglycerides and phosphatidylcholines, suggesting that there are different circadian metabolic phenotypes in the general population. These results have potential implications for lipid metabolism disorders linked to circadian clock disruption.metabolomics | chronobiology T he circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus regulates daily rhythms in behavior and physiology, ensuring that metabolic pathways are temporally coordinated with 24-h cycles of rest-activity and feeding (1). The circadian system controls lipid and carbohydrate homeostasis, thus optimizing energy storage and utilization across the day (2). In humans, this is reflected in part by diurnal variation in glucose tolerance (3, 4), as well as circadian rhythms of glucose, insulin, triglycerides, and adipose-derived hormones in blood (5, 6). At the cellular level, circadian rhythms are generated by transcriptional and posttranscriptional feedback loops, with daily rhythms of cell biology driven by core clock genes and their protein products. The SCN neural rhythm is normally entrained by the 24-h solar cycle, whereas the phase of rhythms in peripheral tissues is thought to be determined primarily by daily rest-activity and/or feeding cycles (7).Disruption of circadian rhythms has been implicated in metabolic syndrome and dyslipidemia (2), and chronic circadian misalignment is thought to contribute to increased risk of cardiovascular disease and obesity in shift workers (8, 9). Although the mechanisms have yet to be fully elucidated, consumption of meals at night is associated with higher postprandial triglyceride levels, compared with meals consumed during the daytime (10, 11). In nocturnal mice, the circadian timing of food intake contribut...

The ECG carries information about a person's vigilance state. Hence, HRV measures could potentially be used to predict when an individual is at increased risk of attentional failure. Our results suggest that HRV monitoring, either alone or in combination with other physiologic measures, could be incorporated into safety devices to warn drowsy operators when their performance is impaired.

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Performance decrements in sustained attention during sleep deprivation associate with instability in behavioral and physiologic measures at baseline. Small individual differences in sustained attention that are present at baseline are amplified during prolonged wakefulness, thus contributing to large between-subjects differences in performance and sleepiness.