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Hull, Joseph Thomas

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Hull

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Joseph Thomas

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Hull, Joseph Thomas
Author's Publications: search.filters.isAuthorOfPublication.96cae56e-1f4c-4024-a20e-c12e582e9bf9

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    Analysis Method and Experimental Conditions Affect Computed Circadian Phase from Melatonin Data
    (Public Library of Science, 2012) Klerman, Hadassa; St. Hilaire, Melissa A.; Gronfier, Claude; Santhi, Nayantara; Kronauer, Richard; Gooley, Joshua James; Hull, Joseph Thomas; Lockley, Steven; Wang, Wei; Klerman, Elizabeth
    Accurate determination of circadian phase is necessary for research and clinical purposes because of the influence of the master circadian pacemaker on multiple physiologic functions. Melatonin is presently the most accurate marker of the activity of the human circadian pacemaker. Current methods of analyzing the plasma melatonin rhythm can be grouped into three categories: curve-fitting, threshold-based and physiologically-based linear differential equations. To determine which method provides the most accurate assessment of circadian phase, we compared the ability to fit the data and the variability of phase estimates for seventeen different markers of melatonin phase derived from these methodological categories. We used data from three experimental conditions under which circadian rhythms - and therefore calculated melatonin phase - were expected to remain constant or progress uniformly. Melatonin profiles from older subjects and subjects with lower melatonin amplitude were less likely to be fit by all analysis methods. When circadian drift over multiple study days was algebraically removed, there were no significant differences between analysis methods of melatonin onsets (P = 0.57), but there were significant differences between those of melatonin offsets (P<0.0001). For a subset of phase assessment methods, we also examined the effects of data loss on variability of phase estimates by systematically removing data in 2-hour segments. Data loss near onset of melatonin secretion differentially affected phase estimates from the methods, with some methods incorrectly assigning phases too early while other methods assigning phases too late; missing data at other times did not affect analyses of the melatonin profile. We conclude that melatonin data set characteristics, including amplitude and completeness of data collection, differentially affect the results depending on the melatonin analysis method used.
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    Short-Wavelength Light Sensitivity of Circadian, Pupillary, and Visual Awareness in Humans Lacking an Outer Retina
    (Cell Press, 2007) Zaidi, Farhan H.; Peirson, Stuart N.; Wulff, Katharina; Brainard, George C.; Gregory-Evans, Kevin; Moseley, Merrick J.; Hull, Joseph Thomas; Aeschback, Daniel; Gooley, Joshua James; Rizzo, Joseph; Czeisler, Charles; Foster, Russell G.; Lockley, Steven
    Summary As the ear has dual functions for audition and balance, the eye has a dual role in detecting light for a wide range of behavioral and physiological functions separate from sight [1–11]. These responses are driven primarily by stimulation of photosensitive retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength (∼480 nm) blue light and remain functional in the absence of rods and cones [8–10]. We examined the spectral sensitivity of non-image-forming responses in two profoundly blind subjects lacking functional rods and cones (one male, 56 yr old; one female, 87 yr old). In the male subject, we found that short-wavelength light preferentially suppressed melatonin, reset the circadian pacemaker, and directly enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of the photopic visual system. In an action spectrum for pupillary constriction, the female subject exhibited a peak spectral sensitivity (λmax) of 480 nm, matching that of the pRGCs but not that of the rods and cones. This subject was also able to correctly report a threshold short-wavelength stimulus (∼480 nm) but not other wavelengths. Collectively these data show that pRGCs contribute to both circadian physiology and rudimentary visual awareness in humans and challenge the assumption that rod- and cone-based photoreception mediate all “visual” responses to light.