D. Max Snodderly

Response Variability of Neurons in Primary Visual Cortex (V1) of Alert Monkeys

Response variability of neurons limits the reliability and resolution of sensory systems. It is generally thought that response variability in the visual system increases at cortical levels, but the causes of the variability have not been identified. We have measured the response variability of neurons in primary visual cortex (V1) of alert monkeys. We recorded from 80 single cells distributed over all V1 layers and from 8 parvocellular cells of the lateral geniculate nucleus. All cells were stimulated with a bar of near-optimal orientation, color, and dimensions while continuously monitoring the eye movements of fixation. To minimize the effects of eye movements, responses that occurred while the eye was relatively steady were selected for analysis. The impulses elicited by each stimulus presentation were counted, and the variance and coefficient of variation were computed. Both measures of response variability were much lower than reported previously for V1 cells of both alert and anesthetized monkeys. Our data show that fixational eye movements cause a large component of response variance in alert monkeys. Moreover, the reliability of V1 neurons is not obviously degraded compared with lateral geniculate nucleus cells. The high reliability of neurons in alert monkeys is consistent with expectations from conventional biophysical models, and it suggests that activity in a modest number of neurons may suffice to form a perceptual decision.

Individual variations in the spatial profile of human macular pigment

Individual variations in the spatial profile of macular pigment (MP) density were measured for 32 subjects. Peak density of MP measured with a 460-nm, 12-arcmin stimulus averaged 0.58, standard deviation (SD) = 0.26, with a range of 0.175 to 1.39. To assess the symmetry of the MP distribution, MP density was measured on the horizontal and vertical meridians at +/-1 deg eccentricity. The density varied by no more than 16% at these four locations, indicating a basically symmetric distribution. Based on a linear interpolation between measured locations, the width of the spatial distribution of MP at half the maximal density averaged 1.03 deg, SD = 0.38, with a range of 0.25 to 1.9 deg. The average spatial profile of MP density across subjects was fitted with both an exponential and a Gaussian function. An exponential decay with eccentricity explained more variance in the data than did a Gaussian function. Assuming an exponential decay with eccentricity, once MP density has been measured in the center of the retina (denoted A), MP density at more eccentric locations (X, deg) can be predicted with a standardized equation (MP = A x 10(-0.42x)). For individual cases, small deviations from an exponential function suggest the existence of minor flanking peaks or shoulders for 40% of the subjects. We also examined the temporal stability of the MP profile of four subjects over a time span of 4-14 months and for a single spatial location for ten subjects over a time span of 1-16 years. These longitudinal data show that differences in MP density among subjects are maintained over time, if dietary patterns are stable.

Cigarette Smoking and Retinal Carotenoids: Implications for Age-related Macular Degeneration

The foveal region of the retina has a yellow pigmentation composed primarily of the carotenoids lutein and zeaxanthin. Past studies have shown that cigarette smoking depresses carotenoid concentrations in the blood. This is the first report on the effects of cigarette smoking on carotenoids in the retina. Macular pigment optical density (MP) was measured psychophysically by comparing foveal and parafoveal sensitivities to light of 460 and 550 nm. General dietary patterns, smoking frequency (cigaretts/day) and personal data were collected by questionnaire. Thirty-four smokers and 34 nonsmokers were compared. Subjects were matched with respect to age, sex, dietary patterns and overall pigmentation (i.e., eye, skin and hair color). The smoking group had a mean MP of 0.16 (SD = 0.12) compared to a mean MP of 0.34 (SD = 0.15) for nonsmokers (P < 0.0001). MP density and smoking frequency were inversely related (r = -0.498 P < 0.001) in a dose-response relationship. A variety of evidence suggests that MP protects the macula from actinic damage both passively (by screening potentially harmful short-wave light) and actively as an antioxidant (e.g., by quenching reactive oxygen species). If smoking causes a reduction in MP density, then smokers may be at risk. Epidemiologic data identifying smoking as a risk factor for the neovascular form of age-related macular degeneration are consistent with this hypothesis.

Sex Differences in Macular Pigment Optical Density:: Relation to Plasma Carotenoid Concentrations and Dietary Patterns

Sex differences in macular pigment (MP) optical density (measured psychophysically) were examined. Concentrations of lutein and zeaxanthin (L and Z) (non-separated) and beta-carotene (BC) in the blood were determined using reverse phase high-performance liquid chromatography. Dietary intake of L and Z, BC, fat, and iron were estimated by questionnaire. Males had 38% higher MP density than females (P < 0.001) despite similar plasma carotenoid concentrations and similar dietary intake (except for fat). Dietary intake of carotenoids, fat and iron, as well as plasma concentrations of L and Z were positively related to MP density in males. Conversely, only plasma L and Z was related to MP density for females, and dietary fat was negatively related to MP density. Sex differences in protection of the retina by MP and in the relationship between the retina, blood and diet could be a factor in the incidence of retinal diseases, especially age-related macular degeneration.

Cognitive findings of an exploratory trial of docosahexaenoic acid and lutein supplementation in older women

Abstract Introduction: Low dietary intake of docosahexaenoic acid (DHA) and/or foods rich in lutein may be associated with increased risk of cognitive decline in the elderly. Subjects and methods: The cognitive benefit of DHA and lutein in unimpaired elder women was explored in the context of a 4-month, double-blind, intervention trial of DHA and lutein supplementation for eye health. Forty-nine women (aged 60–80 years) were randomized to receive DHA (800 mg/day; n = 14), lutein (12 mg/day; n = 11), a combination of DHA and lutein (n = 14) or placebo (n = 10). Subjects underwent cognitive tests measuring verbal fluency, memory, processing speed and accuracy, and self-reports of mood at randomization and upon completion of the trial. Results: Following supplementation, verbal fluency scores improved significantly in the DHA, lutein, and combined treatment groups (P < 0.03). Memory scores and rate of learning improved significantly in the combined treatment group (P < 0.03), who also displayed a trend toward more efficient learning (P = 0.07). Measures of mental processing speed, accuracy and mood were not affected by supplementation. Conclusions: These exploratory findings suggest that DHA and lutein supplementation may have cognitive benefit for older adults.

A dissociation between brain activity and perception: chromatically opponent cortical neurons signal chromatic flicker that is not perceived.

When two isoluminant colors alternate at frequencies > 10 Hz, we perceive only one fused color with a minimal sensation of brightness flicker. In spite of the perception of color fusion, color opponent (CO) cells at early stages of the visual pathway are known to respond to chromatic flicker at frequencies far exceeding the perceptual fusion frequency. To explain color fusion, several groups have predicted that CO cells in V1-unlike the retina and lateral geniculate nucleus-should not follow high-frequency flicker. To test this prediction we recorded from 12 CO cells in various V1 layers. We found, contrary to expectations, that these neurons follow high frequency flicker well above heterochromatic fusion frequencies. All followed 15 Hz flicker and 10/12 followed 30 Hz flicker. For three cells, we tested 60 Hz luminance flicker and found clear responses. We thus present evidence of cortical activity in alert, trained monkeys that is clearly representing visual stimulation, yet is not perceived. Our data call into question explanations of perceptual phenomena that invoke a low temporal frequency cut-off of CO cells in V1 to account for the failure to perceive fast temporal changes in the chromatic domain.

Selective activation of visual cortex neurons by fixational eye movements: implications for neural coding.

During normal vision, when subjects attempt to fix their gaze on a small stimulus feature, small fixational eye movements persist. We have recorded the impulse activity of single neurons in primary visual cortex (V1) of macaque monkeys while their fixational eye movements moved the receptive-field activating region (AR) over and around a stationary stimulus. Three types of eye movement activation were found. (1) Saccade cells discharged when a fixational saccade moved the AR onto the stimulus, off the stimulus, or across the stimulus. (2) Position/drift cells discharged during the intersaccadic (drift) intervals and were not activated by saccades that swept the AR across the stimulus without remaining on it. To activate these neurons, it was essential that the AR be placed on the stimulus and many of these cells were selective for the sign of contrast. They had smaller ARs than the other cell types. (3) Mixed cells fired bursts of activity immediately following saccades and continued to fire at a lower rate during intersaccadic intervals. The tendency of each neuron to fire transient bursts or sustained trains of impulses following saccades was strongly correlated with the transiency of its response to stationary flashed stimuli. For one monkey, an extraretinal influence accompanying fixational saccades was identified. During natural viewing, the different eye movement classes probably make different contributions to visual processing. Position/drift neurons are well suited for coding spatial details of the visual scene because of their small AR size and their selectivity for sign of contrast and retinal position. However, saccade neurons transmit information that is ambiguous with respect to the spatial details of the retinal image because they are activated whether the AR lands on a stimulus contour, or the AR leaves or crosses the contour and lands in another location. Saccade neurons may be involved in constructing a stable world in spite of incessant retinal image motion, as well as in suppressing potentially confusing input associated with saccades.

Saccades and drifts differentially modulate neuronal activity in V1: Effects of retinal image motion, position, and extraretinal influences

In natural vision, continuously changing input is generated by fast saccadic eye movements and slow drifts. We analyzed effects of fixational saccades, voluntary saccades, and drifts on the activity of macaque V1 neurons. Effects of fixational saccades and small voluntary saccades were equivalent. In the presence of a near-optimal stimulus, separate populations of neurons fired transient bursts after saccades, sustained discharges during drifts, or both. Strength, time course, and selectivity of activation by fast and slow eye movements were strongly correlated with responses to flashed or to externally moved stimuli. These neuronal properties support complementary functions for post-saccadic bursts and drift responses. Local post-saccadic bursts signal rapid motion or abrupt change of potentially salient stimuli within the receptive field; widespread synchronized bursts signal occurrence of a saccade. Sustained firing during drifts conveys more specific information about location and contrast of small spatial features that contribute to perception of fine detail. In addition to stimulus-driven responses, biphasic extraretinal modulation accompanying saccades was identified in one third of the cells. Brief perisaccadic suppression was followed by stronger and longer-lasting enhancement that could bias perception in favor of saccade targets. These diverse patterns of neuronal activation underlie the dynamic encoding of our visual world.

Nutritional manipulation of primate retinas, V: effects of lutein, zeaxanthin, and n-3 fatty acids on retinal sensitivity to blue-light-induced damage.

PURPOSE Blue-light photooxidative damage has been implicated in the etiology of age-related macular degeneration (AMD). The macular pigment xanthophylls lutein (L) and zeaxanthin (Z) and n-3 fatty acids may reduce this damage and lower the risk of AMD. This study investigated the effects of the lifelong absence of xanthophylls followed by L or Z supplementation, combined with the effects of n-3 fatty acid deficiency, on acute blue-light photochemical damage. METHODS Subjects included eight rhesus monkeys with no lifelong intake of xanthophylls and no detectable macular pigment. Of these, four had low n-3 fatty acid intake and four had adequate intakes. Control subjects had typical L, Z, and n-3 fatty acid intake. Retinas received 150-μm-diameter exposures of low-power 476-nm laser light at 0.5 mm (∼2°) eccentricity, which is adjacent to the macular pigment peak, and parafoveally at 1.5 mm (∼6°). Exposures of xanthophyll-free animals were repeated after supplementation with pure L or Z for 22 to 28 weeks. Ophthalmoscopically visible lesion areas were plotted as a function of exposure energy, with greater slopes of the regression lines indicating greater sensitivity to damage. RESULTS In control animals, the fovea was less sensitive to blue-light-induced damage than the parafovea. Foveal protection was absent in xanthophyll-free animals but was evident after supplementation. In the parafovea, animals low in n-3 fatty acids showed greater sensitivity to damage than animals with adequate levels. CONCLUSIONS After long-term xanthophyll deficiency, L or Z supplementation protected the fovea from blue light-induced damage, whereas adequate n-3 fatty acid levels reduced the damage in the parafovea.

Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin

Purpose. Although oxidative stress may play an important role in the development of age-related cataract, the degree of protection reported for antioxidant vitamins and carotenoids has been inconsistent across studies. These varied results may be due in part to the lack of good biomarkers for measuring the long-term nutritional status of the eye. The present experiments investigated the relationship between retinal carotenoids (i.e., macular pigment), used as a long-term measure of tissue carotenoids, and lens optical density, used as an indicator of lens health. Methods. Macular pigment (460 nm) and lens (440, 500, and 550 nm) optical density were measured psychophysically in the same individuals. Groups of younger subjects—7 females (ages 24 to 36 years), and 5 males (ages 24 to 31 years)—were compared with older subjects—23 older females (ages 55 to 78 years), and 16 older males (ages 48 to 82 years). Results. Lens density (440 nm) increased as a function of age (r=0.65, p<0.001), as expected. For the oldest group, a significant inverse relationship (y=1.53−0.83x, r=−0.47, p<0.001) was found between macular pigment density (440 nm) and lens density (440 nm). No relationship was found for the youngest group (p<0.42). Conclusions. The main finding of this study was an age-dependent, inverse relationship between macular pigment density and lens density. Macular pigment is composed of lutein and zeaxanthin, the only two carotenoids that have been identified in the human lens. Thus, an inverse relationship between these two variables suggests that lutein and zeaxanthin, or other dietary factors with which they are correlated, may retard age-related increases in lens density.