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Biomedical subjects

R E Kronauer

Publications and source records attributed to R E Kronauer.

At least 55 records · Page 3Linked to original sources
PubMed1993

Colour is what the eye sees best.

It has been argued by Watson, Barlow and Robson that the visual stimulus that humans detect best specifies the spatial-temporal structure of the receptive field of the most sensitive visual neurons. To investigate 'what the eye sees best' they used stimuli that varied in luminance alone. Because the most abundant primate retinal ganglion cells, the P cells, are colour-opponent, we might expect that a coloured pattern would also be detected well. We generalized Watson et al.'s study to include variations in colour as well as luminance. We report here that our best detected coloured stimulus was seen 5-9-fold better than our best luminance spot and 3-8-fold better than Watson's best luminance stimulus. The high sensitivity to colour is consistent with the prevalence and high colour contrast-gain of retinal P cells, and may compensate for the low chromatic contrasts typically found in natural scenes.

Color Perception↗
PubMed1993

Circadian sleep regulation in the absence of light perception: chronic non-24-hour circadian rhythm sleep disorder in a blind man with a regular 24-hour sleep-wake schedule.

Sleep disturbances and the failure to entrain circadian rhythms to the 24-hour day have been reported in the majority of totally blind subjects. The present case study of a totally blind man with a well-documented recurring sleep disturbance was designed to investigate the mutual relationship between sleep and the circadian timing system. The 63-year-old subject, a high school teacher with a regular work schedule, had suffered from cyclically recurring insomnia for the past 28 years. Analysis of a sleep log that he had kept for the past 15 years suggested that his circadian rhythms were not entrained to the 24-hour day. During a 3-month inpatient study, the period of the endogenous circadian pacemaker was assessed by analysis of ambulatory core body temperature, urinary excretion and a series of estimates of the phase of core body temperature cycles and plasma cortisol levels during constant routines. All circadian markers revealed periods in the range of 24.22-24.27 hours, with no evidence for a modulation of the observed periods by the sleep-wake cycle. During this 3-month inpatient study, a complete cycle of the subject's sleep disturbance and remission was polysomnographically documented while the subject lived on a regular 24-hour schedule. Because the subject's circadian rhythms were free-running and his sleep times were fixed, sleep occurred at virtually all circadian phases. Analysis of sleep latency, REM sleep latency, sleep duration, wake in sleep episode and REM sleep during sleep episode revealed a strong modulation by circadian phase. These findings in this blind man suggest that: 1) the period of his cyclically recurring sleep disturbance is directly related to the nonentrained period of an endogenous circadian pacemaker that drives circadian variation in core body temperature, urinary excretion, plasma cortisol and sleep propensity; 2) both his sleep structure and the severity of his daily sleep disruption are directly related to circadian phase and 3) his circadian pacemaker, which has an endogenous period that deviates only 0.2-0.3 hours from 24 hours, cannot be entrained by periodic daily exposure to nonphotic time cues, including a very regular 24-hour sleep-wake schedule.

Blindness↗
PubMed1991

Light-induced suppression of endogenous circadian amplitude in humans.

Winfree reported 20 years ago the intriguing finding that a light stimulus of a critical strength applied at a critical circadian phase could essentially stop the circadian clock in Drosophila pseudo-obscura by resetting the circadian oscillator close to its singularity (a phaseless position at which the amplitude of circadian oscillation is zero). Since then, similar observations of attenuated circadian amplitude in response to critical stimuli have been limited to unicells, insects and plants. Our recent demonstration that the phase of the human circadian pacemaker could be inverted using an unconventional three-cycle stimulus led us to investigate whether critically timed exposure to a more moderate stimulus could drive that oscillator towards its singularity. Here we report that exposure of humans to fewer cycles of bright light, centred around the time at which the human circadian pacemaker is most sensitive to light-induced phase shifts, can markedly attenuate endogenous circadian amplitude. In some cases this results in an apparent loss of rhythmicity, as expected to occur in the region of singularity.

Adolescent↗
PubMed1991

Temporal phase response of the short-wave cone signal for color and luminance.

A chromatic discrimination paradigm was used to measure the temporal phase of the S (short-wave cone) signal relative to the L--M (long-wave cone minus middle-wave cone) signal. Suprathreshold equiluminant red-green flicker that stimulates the L--M mechanism was presented on a steady, intense yellow-green adapting field. Violet flicker that stimulates the S cones was added to the red-green flicker at different temporal phase angles, and the violet modulation depth was varied to achieve a chromatic discrimination threshold. A template was fitted to the data relating thresholds to phase: the location of the template symmetry axis showed that the S signal lagged L--M by about 75-90 degrees at 10 Hz. This is about one half the phase lag obtained for luminance or motion discrimination. The phase discrepancy shows that there are separate luminance and chromatic mechanisms receiving S cone inputs. The hue of the flicker in the present study varied strongly with phase angle, with the positive and negative excursions of the S cone signal producing a reddish-blue and greenish-yellow, respectively, and these colors combined with the reddish and greenish hues produced by the L--M signal. The observed phase shift, and measured color appearance of the combined flicker, account for the colors seen on a radially segmented disk of Munsell hues when rotated: the colors differ strikingly depending on the direction of rotation.

Adaptation, Ocular↗
PubMed1991

Detection uncertainty and the facilitation of chromatic detection by luminance contours.

A suprathreshold luminance flash (1 degree, 200 msec) on a large uniform yellow field facilitates detection of a coincident (1 degree, 200 msec) red or green equiluminant flash and approximately linearizes the psychometric function for detecting the chromatic flash. The facilitation is produced by the suprathreshold contour created by the luminance flash. We tested whether the contour facilitates detection by reducing spatiotemporal uncertainty in detecting the chromatic flash. Uncertainty increase false alarms, and this effect can be factored out by correcting yes-no psychometric functions for guessing. Uncertainty also alters the shape of the receiver operating characteristic. Measurements of yes-no psychometric functions and receiver operating characteristics do not support the uncertainty reduction hypothesis.

Color Perception↗
PubMed1990

Exposure to bright light and darkness to treat physiologic maladaptation to night work.

Working at night results in a misalignment between the sleep-wake cycle and the output of the hypothalamic pacemaker that regulates the circadian rhythms of certain physiologic and behavioral variables. We evaluated whether such physiologic maladaptation to nighttime work could be prevented effectively by a treatment regimen of exposure to bright light during the night and darkness during the day. We assessed the functioning of the circadian pacemaker in five control and five treatment studies in order to assess the extent of adaptation in eight normal young men to a week of night work. In the control studies, on the sixth consecutive night of sedentary work in ordinary light (approximately 150 lux), the mean (+/- SEM) nadir of the endogenous temperature cycle continued to occur during the night (at 3:31 +/- 0:56 hours), indicating a lack of circadian adaptation to the nighttime work schedule. In contrast, the subjects in the treatment studies were exposed to bright light (7000 to 12,000 lux) at night and to nearly complete darkness during the day, and the temperature nadir shifted after four days of treatment to a significantly later, midafternoon hour (14:53 +/- 0:32; P less than 0.0001), indicating a successful circadian adaptation to daytime sleep and nighttime work. There were concomitant shifts in the 24-hour patterns of plasma cortisol concentration, urinary excretion rate, subjective assessment of alertness, and cognitive performance in the treatment studies. These shifts resulted in a significant improvement in both alertness and cognitive performance in the treatment group during the night-shift hours. We conclude that maladaptation of the human circadian system to night work, with its associated decline in alertness, performance, and quality of daytime sleep, can be treated effectively with scheduled exposure to bright light at night and darkness during the day.

Adaptation, Physiological↗
PubMed1990

Visual interactions with luminance and chromatic stimuli.

The visibility of a 1 degree, 200-msec flash on a large yellow field was measured as a function of the intensity of a coincident pedestal flash (a flash that was the same in both temporal intervals of a two-alternative forced-choice trial). The various flashes were incremental (+Lum) or decremental (-Lum) yellow luminance flashes or green (+Chr) or red (-Chr) isoluminant chromatic flashes. With uncrossed conditions (Lum tests on Lum pedestals or Chr tests on Chr pedestals), we obtained the conventional dipper function, that is, the function of threshold test intensity was highly asymmetric about zero pedestal intensity, and strong pedestals induced strong masking. Crossed conditions produced neither effect: for example, with Chr tests on Lum pedestals, there was no dipper function: the function of threshold test intensity was symmetric about zero pedestal intensity, and strong pedestals produced no masking. Instead, the suprathreshold luminance pedestals facilitated chromatic detection by as much as 2-3X and also linearized the chromatic psychometric function, further enhancing sensitivity to weak chromatic stimuli. (Chromatic sensitivity on the suprathreshold luminance pedestal was approximately 25X higher than luminance sensitivity on the uniform field.) A pedestal consisting of a thin luminance ring that surrounded the chromatic test produced facilitation equal to that of the uniform-luminance pedestal: the pedestal may thus act to demarcate the test spatially and promote chromatic comparison with the surround. Removing the uniform yellow surround eliminated this crossed facilitation but did not eliminate the uncrossed facilitation (the dipper function), suggesting that different mechanisms mediate the crossed and uncrossed facilitations.

Color↗
PubMed1989

Bright light induction of strong (type 0) resetting of the human circadian pacemaker.

The response of the human circadian pacemaker to light was measured in 45 resetting trials. Each trial consisted of an initial endogenous circadian phase assessment, a three-cycle stimulus which included 5 hours of bright light per cycle, and a final phase assessment. The stimulus induced strong (type 0) resetting, with responses highly dependent on the initial circadian phase of light exposure. The magnitude and direction of the phase shifts were modulated by the timing of exposure to ordinary room light, previously thought to be undetectable by the human pacemaker. The data indicate that the sensitivity of the human circadian pacemaker to light is far greater than previously recognized and have important implications for the therapeutic use of light in the management of disorders of circadian regulation.

Adult↗
PubMed1987

Chromatic suppression of cone inputs to the luminance flicker mechanism.

Eisner and MacLeod [J. opt. Soc. Am. 71, 705-718 (1981)] showed that intense green and red chromatic adapting fields may suppress respectively the M and L cone input to the luminance mechanism by a factor considerably greater than Weber's law. We obtained evidence for such chromatic suppression by measuring complete detection contours for different ratios of red and green test lights presented in rapid flicker in the center of a uniform field. The detection contours represent thresholds as the quantal modulation of the M and L cones normalized by the quantal catch owing to the field. Luminance flicker mechanisms were identified by sections of the contours where detection was controlled by a linear sum of the M and L cone test signals. The slope of these sections indicated that intense red fields selectively suppressed the L cone input to the luminance mechanism by a factor greater than Weber's law; evidence was much less firm for an analogous suppression of the M cone input by intense green fields. The shape of the detection contours also suggests that intense red fields, which differentially light-adapt the M and L cones, may produce a moderate temporal phase-shift between the M and L cone signals. The shape of the temporal MTF of the M cone and the L cone input to the luminance mechanism may be determined at the cone stage, with the absolute sensitivity (vertical scaling) being partially dependent on selective chromatic suppression of the cone inputs owing to the intense chromatic field. Luminance and red-green chromatic temporal sensitivity functions are presented in terms of the M and L cone quantal modulations. Chromatic sensitivity progressively rises above luminance sensitivity as temporal frequency is gradually lowered below 15 Hz, with the consequence that 'contrast sensitivity' may be much higher for color than for luminance.

Adaptation, Ocular↗
PubMed1987

Circadian pacemaker interferes with sleep onset at specific times each day: role in insomnia.

The human circadian pacemaker modulates our desire and ability to fall asleep at different times of day. To study this circadian component of sleep tendency, we have analyzed the sleep-wake patterns recorded from 15 free-running subjects in whom the sleep-wake cycle spontaneously desynchronized from the circadian rhythm of body temperature. The analysis indicates that the distribution of sleep onsets during free run is bimodal, with one peak at the temperature trough and, contrary to previous reports, a second peak 9-10 h later. Furthermore, there are two consistent zones in the circadian temperature cycle during which normal subjects rarely fall asleep. We hypothesize that this bimodal rhythm of sleep tendency, revealed under free-running conditions, maintains the same fixed phase relation to the circadian temperature cycle during 24-h entrainment. This would imply that normally entrained individuals should experience a peak of sleep tendency in the midafternoon and a zone of minimal sleep tendency approximately 1-3 h before habitual bedtime. Our temporal isolation data thereby account quantitatively for the timing of the afternoon siesta and suggest that malfunctions of the phasing of the circadian pacemaker may underlie the insomnia associated with sleep-scheduling disorders.

Chronobiology Phenomena↗
PubMed1987

Biologic rhythm disorders, depression, and phototherapy. A new hypothesis.

Disturbances of the circadian timing system are implicated in the pathogenesis of numerous clinical syndromes, including sleep and affective disorders. Abnormalities of circadian rhythms can now be directly measured in the clinical laboratory and potentially corrected. Sleep scheduling disorders are most commonly due to phase misalignments between the endogenous circadian pacemaker and the socioenvironmental schedule. Current research is increasing our understanding of the influence of bright light exposure on the circadian timing system and has begun to be used successfully in the management of these conditions. There is substantial evidence that abnormalities of the circadian timing system are associated with depression. However, the application of new biologic rhythm diagnostic techniques would be required to establish whether circadian dysfunction is involved in the pathogenesis of these conditions. We propose a new hypothesis that phototherapy for seasonal depression may act by increasing an abnormally low circadian amplitude in those patients, such as that reported in endogenously depressed patients. The powerful effect of light on the circadian system indicates that phototherapy may become an important tool in the management of disorders of circadian etiology.

Circadian Rhythm↗
PubMed1986

Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle.

Human circadian rhythms were once thought to be insensitive to light, with synchronization to the 24-hour day accomplished either through social contacts or the sleep-wake schedule. Yet the demonstration of an intensity-dependent neuroendocrine response to bright light has led to renewed consideration of light as a possible synchronizer of the human circadian pacemaker. In a laboratory study, the output of the circadian pacemaker of an elderly woman was monitored before and after exposure to 4 hours of bright light for seven consecutive evenings, and before and after a control study in ordinary room light while her sleep-wake schedule and social contacts remained unchanged. The exposure to bright light in the evening induced a 6-hour delay shift of her circadian pacemaker, as indicated by recordings of body temperature and cortisol secretion. The unexpected magnitude, rapidity, and stability of the shift challenge existing concepts regarding circadian phase-resetting capacity in man and suggest that exposure to bright light can indeed reset the human circadian pacemaker, which controls daily variations in physiologic, behavioral, and cognitive function.

Aged↗
PubMed1986

Circadian regulation dominates homeostatic control of sleep length and prior wake length in humans.

During prolonged temporal isolation in caves or windowless rooms, human subjects often develop complicated sleep-wake patterns. Seeking lawful structure in these patterns, we have reanalyzed the spontaneous timing of 359 sleep-wake cycles recorded from 15 internally desynchronized human subjects. The observed sleep-wake patterns obey a simple rule: The phase of the circadian temperature rhythm at bedtime determines the lengths of both prior wake (alpha) and subsequent sleep (rho). From this rule we derive an average alpha:rho relationship that depends on circadian phase. The relationship reconciles the established negative alpha:rho correlation observed in synchronized subjects with the positive alpha:rho correlation found in desynchronized subjects. Our most surprising result concerns the residual deviations of alpha and rho from their circadian phase-adjusted mean values. We report that there is no significant positive correlation between the residuals of alpha and rho, contrary to the prediction of restorative models of sleep duration. Our findings illuminate the mechanisms underlying sleep regulation and provide much-needed tests of mathematical models of the sleep-wake cycle.

Adult↗
PubMed1985

Second-site adaptation in the red-green chromatic pathways.

On different chromatic adapting fields, thresholds were measured with a 1.2 deg flash consisting of simultaneous incremental and decremental red and green components that stimulate the M and L cones in any desired ratio. Thresholds were plotted in normalized coordinates in which the quantal change in the M and L cones due to the flash was divided by the quantal catch due to the field. Detection contours for a wide range of test flashes provide evidence for luminance and chromatic mechanisms that respectively respond to the sum and difference of the M and L cone signals. Field color has little influence on the luminance mechanism but strongly affects chromatic detection, with sensitivity being maximal on yellow fields and declining slightly on green fields and declining strongly on red fields. Similar effects were obtained for long (200 msec) and very brief flashes, although the shape of the contours differed considerably. The results provide evidence for a second adaptation site within the red-green chromatic pathways, similar to the second-site in the S cone pathways. Chromatic fields (green and red) polarize the site and reduce sensitivity to chromatic flashes.

Adaptation, Ocular↗
PubMed1985

Phase shifting two coupled circadian pacemakers: implications for jet lag.

Flights across time zones produce an abrupt displacement of the environmental time cues (zeitgebers), and the endogenous circadian timing system resynchronizes only gradually to the new schedule. A coupled two-oscillator model can simulate the human circadian system in temporal isolation and in artificial zeitgeber cycles. The model is here shown to explain the major features of resynchronization of circadian rhythms after time zone shifts, i.e., the rate of adjustment depends on the rhythm being measured, the number of time zones crossed, the flight direction (eastward or westward), and the strength of the zeitgebers in the new time zone. Investigations of the contribution of different model parameters to system performances suggest that intersubject differences in pacemaker periods may be a major factor in the observed variability in the effects of time zone shifts on circadian rhythms. With individualized period estimate the models can simulate case studies in which four subjects recorded their sleep-wake and core body temperature rhythms throughout simple and complex patterns of transmeridian flights.

Body Temperature↗
PubMed1984

Adaptive processes controlling sensitivity of short-wave cone pathways to different spatial frequencies.

The sensitivity of the short-wave cone pathways was measured with violet interference gratings on monochromatic adapting fields. Spectral field sensitivity functions for test gratings of 2, 4 and 8 c/deg approximately matched Stiles' pi 3 function, which presumably reflects light-adaptation of the short-wave cones. Previous work had suggested that field sensitivity varies as a function of test spatial frequency, but this now seems an artifact of spatial adaptation. (The present study shows the pathway is highly susceptible to spatial adaptation induced by fine patterns.) For various spatial frequencies that affect the short-wave pathway, signals also pass through a cancellate adaptation site where signals from the short-wave and the middle- and long-wave cones act in opposition. Transient inputs in either opponent direction polarize or desensitize the opponent site. Additional transient inputs of the opposite sign then reduce the polarization and increase sensitivity. Such effects were demonstrated with test gratings as high as 12 c/deg. Transient effects at the opponent site are particularly evident at higher spatial frequencies.

Adaptation, Ocular↗