Biology subjects

Spitschan, M.

Publications and source records attributed to Spitschan, M..

44 records · Page 3Linked to original sources

bioRxiv2020

Rest-activity cycles and melatonin phase angle of circadian entrainment in people without cone-mediated vision

BackgroundLight exposure entrains the circadian clock through the intrinsically photosensitive retinal ganglion cells, which sense light in addition to the cones and rods. In congenital achromatopsia (ACHM; prevalence 1:30-50,000), the cone system is non-functional, resulting in severe light avoidance and photophobia at daytime light levels. How this condition affects circadian and neuroendocrine responses to light is not known. MethodsIn genetically confirmed ACHM patients (n=7; age 30-72 years; 6 women, 1 male), we examined survey-assessed sleep/circadian phenotype (PSQI, ESS, MEQ, MCTQ), self-reported visual function (NEI-VFQ-25), sensitivity to light (VLSQ-8) and use of spectral filters that modify chronic light exposure. In all but one patient, we measured rest-activity cycles using actigraphy over 3 weeks and measured the melatonin phase angle of entrainment using the dim-light melatonin onset (DLMO). ResultsACHM patients experience a severely attenuated light-dark cycle due to severe light sensitivity and habitual use of filters to reduce retinal illumination. In aggregate, both MEQ and MCTQ indicated a tendency to late chronotype. We found regular rest-activity patterns in all patients and normal phase angles of entrainment in participants with a measurable DLMO. ConclusionsOur results reveal that a functional cone system and exposure to daytime light intensities are not necessary for regular behavioural and hormonal entrainment, even when survey-assessed sleep and circadian phenotype indicated a tendency for a late chronotype and sleep problems in our ACHM cohort. Our results can be explained by an adaptation mechanism in circadian photoreception which adjusts to the range of habitual light exposures.

neuroscience↗

bioRxiv2019

No evidence for an S cone contribution to the human circadian response to light

Exposure to even moderately bright, short-wavelength light in the evening can strongly suppress the production of melatonin and can delay our circadian rhythm. These effects are mediated by the retinohypothalamic pathway, connecting a subset of retinal ganglion cells to the circadian pacemaker in the suprachiasmatic nucleus (SCN) in the brain. These retinal ganglion cells directly express the photosensitive protein melanopsin, rendering them intrinsically photosensitive (ipRGCs). But ipRGCs also receive input from the classical photoreceptors -- the cones and rods. Here, we examined whether the short-wavelength-sensitive (S) cones contribute to circadian photoreception by using lights which differed exclusively in the amount of S cone excitation by almost two orders of magnitude (ratio 1:83), but not in the excitation of long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cones, rods, and melanopsin. We find no evidence for a role of S cones in the acute alerting and melatonin supressing response to evening light exposure, pointing to an exclusive role of melanopsin in driving circadian responses.

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bioRxiv2019

Duration invariance of the human circadian system response to pulsed light

The melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are characterised by a delayed off-time following light offset. Here, we exploited this unusual physiologic property to characterise the exquisite sensitivity of the human circadian system to flashed light. In a 34-hour in-laboratory between-subjects design, we examined variable-intensity (3-9500 photopic lux; n=28 participants) full-field flashes at fixed duration (2 ms), and variable-duration (10 s-10 s) full-field flashes at fixed intensity (2000 photopic lux; n=31 participants) delivered using eye masks. We measured the circadian phase shift of the dim-light melatonin onset (DLMO) on the subsequent evening, acute melatonin suppression, objective alertness, and subjective sleepiness during the flash sequence. We find a clear dose-response relationship between flash intensity and the induced circadian phase shift, with an approximate increase of 10 minutes of phase delay for each ten-fold increase in photopic illuminance, but no parametric relationship between flash duration and induced circadian phase shift.

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bioRxiv2019

Photoreceptor inputs into pupil control

The size of the pupil depends on light level. Watson & Yellott (2012) developed a unified formula to predict pupil size from luminance, field diameter, age, and number of eyes. Luminance reflects input from the L and M cones in the retina but ignores the contribution of intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin, which are known to control the size of the pupil. We discuss the role of melanopsin in controlling pupil size by reanalysing an extant data set. We confirm that melanopsin-weighted quantities, in conjunction with Watson & Yellotts formula, adequately model intensity-dependent pupil size. We discuss the contributions of other photoreceptors into pupil control.

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bioRxiv2019

Visual and non-visual properties of filters manipulating short-wavelength light

Optical filters and tints manipulating short-wavelength light (so-called \"blue-blocking\" or \"blue-attenuating\") are used as a remedy for a range of ocular, retinal, neurological and psychiatric disorders. In many cases, the only available quantification of the optical effects of a given optical filter is the spectral transmittance, which specifies the amount of light transmitted as a function of wavelength. Here, we propose a novel physiologically relevant and retinally referenced framework for quantifying the visual and non-visual effects of these filters, incorporating the attenuation of luminance (luminance factor), the attenuation of melanopsin activation (melanopsin factor), the shift in colour, and the reduction of the colour gamut (gamut factor). We examined a novel data base of optical transmittance filters (n=120) which were digitally extracted from a variety of sources and find a large diversity in the alteration of visual and non-visual properties. We suggest that future studies and examinations of the physiological effects of optical filters quantify the visual and non-visual effects of the filters beyond the spectral transmittance, which will eventually aid in developing a mechanistic understanding of how different filters affect physiology.

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bioRxiv2018

Pupil responses to hidden photoreceptor-specific modulations in movies

Under typical daytime light levels, the human pupillary light response (PLR) is driven by the activity of the L, M, and S cones, and melanopsin expressed in the so-called intrinsically photosensitive retinal ganglion cells (ipRGCs). However, the importance of each of these photoreceptive mechanisms in defining pupil size under real-world viewing conditions remains to be established. To address this question, we embedded photoreceptor-specific modulations in a movie displayed using a novel projector-based five-primary spatial stimulation system, which allowed for the precise control of photoreceptor activations in time and space. We measured the pupillary light response in eleven observers, who viewed short cartoon movies which contained hidden low-frequency (0.25 Hz) silent-substitution modulations of the L, M and S cones (no stimulation of melanopsin), melanopsin (no stimulation of L, M and S cones), both L, M, and S cones and melanopsin or no modulation at all. We find that all photoreceptors active at photopic light levels regulate pupil size under this condition. Our data imply that embedding modulations in photoreceptor contrast could provide a method to manipulate key adaptive aspects of the human visual system in everyday, real-world activities such as watching a movie.

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bioRxiv2018

Pulses of melanopsin-directed contrast produce highly reliable pupil responses that are insensitive to a change in background radiance

PurposeTo measure the pupil response to pulses of melanopsin-directed contrast, and compare this response to those evoked by cone-directed contrast and spectrally-narrowband stimuli.\n\nMethods3-second unipolar pulses were used to elicit pupil responses in human subjects across 3 sessions. Thirty subjects were studied in Session 1, and most returned for Sessions 2 and 3. The stimuli of primary interest were \"silent substitution\" cone- and melanopsin-directed modulations. Red and blue narrowband pulses delivered using the post-illumination pupil response (PIPR) paradigm were also studied. Sessions 1 and 2 were identical, while Session 3 involved modulations around higher radiance backgrounds. The pupil responses were fit by a model whose parameters described response amplitude and temporal shape.\n\nResultsGroup average pupil responses for all stimuli overlapped extensively across Sessions 1 and 2, indicating high reproducibility. Model fits indicate that the response to melanopsin-directed contrast is prolonged relative to that elicited by cone-directed contrast. The group average cone- and melanopsin-directed pupil responses from Session 3 were highly similar to those from Sessions 1 and 2, suggesting that these responses are insensitive to background radiance over the range studied. The increase in radiance enhanced persistent pupil constriction to blue light.\n\nConclusionsThe group average pupil response to stimuli designed through silent substitution provides a reliable probe of the function of a melanopsin-mediated system in humans. As disruption of the melanopsin system may relate to clinical pathology, the reproducibility of response suggests that silent substitution pupillometry can test if melanopsin signals differ between clinical groups.

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bioRxiv2017

The Human Visual Cortex Response To Melanopsin-Directed Stimulation Is Accompanied By A Distinct Perceptual Experience

The photopigment melanopsin supports reflexive visual functions in people, such as pupil constriction and circadian photoentrainment. What contribution melanopsin makes to conscious visual perception is less studied. We devised a stimulus that targeted melanopsin separately from the cones using pulsed (3 s) spectral modulations around a photopic background. Pupil-lometry confirmed that the melanopsin stimulus drives a retinal mechanism distinct from luminance. In each of four subjects, a functional MRI response in area V1 was found. This response scaled with melanopic contrast and was not easily explained by imprecision in the silencing of the cones. Twenty additional subjects then observed melanopsin pulses and provided a structured rating of the perceptual experience. Melanopsin stimulation was described as an unpleasant, blurry, minimal brightening that quickly faded. We conclude that isolated stimulation of melanopsin is likely associated with a response within the cortical visual pathway and with an evoked conscious percept.

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