Efficient measurements for the dynamic range of human lightness perception.

PURPOSE: Patients with an eye disease often report nyctalopia, hemianopia, and/or photophobia. We hypothesized that such symptoms are related to the disease impacting the dynamic range of lightness perception (DRL). However, there is currently no standardized approach for measuring DRL for clinical use. We developed an efficient measurement method to estimate DRL. STUDY DESIGN: Clinical trial METHODS: Fifty-five photophobic patients with eye disease and 46 controls participated. Each participant judged the appearance of visual stimuli, a thick bar with luminance that gradually changed from maximum to minimum was displayed on uniform background. On different trials the background luminance changed pseudo-randomly between three levels. The participants repeatedly tapped a border on the bar that divided the appearance of grayish white/black and perfect white/black. We defined the DRL as the ratio between the luminance values at the tapped point of the border between gray and white/black. RESULTS: The mean DRL of the patients was approximately 15 dB, significantly smaller than that of the controls (20 dB). The center of each patient's DRL shift depending on background luminance, which we named index of contextual susceptibility (iCS), was significantly larger than controls. The DRL of retinitis pigmentosa was smaller than controls for every luminance condition. Only the iCS of glaucoma was significantly larger than controls. CONCLUSIONS: This measurement technique detects an abnormality of the DRL. The results support our hypothesis that the DRL abnormality characterizes lightness-relevant symptoms that may elucidate the causes of nyctalopia, hemeralopia, and photophobia.

V1 Projection Zone Signals in Human Macular Degeneration Depend on Task Despite Absence of Visual Stimulus.

Identifying the plastic and stable components of the visual cortex after retinal loss is an important topic in visual neuroscience and neuro-ophthalmology.1-5 Humans with juvenile macular degeneration (JMD) show significant blood-oxygen-level-dependent (BOLD) responses in the primary visual area (V1) lesion projection zone (LPZ),6 despite the absence of the feedforward signals from the degenerated retina. Our previous study7 reported that V1 LPZ responds to full-field visual stimuli during the one-back task (OBT), not during passive viewing, suggesting the involvement of task-related feedback signals. Aiming to clarify whether visual inputs to the intact retina are necessary for the LPZ responses, here, we measured BOLD responses to tactile and auditory stimuli for both JMD patients and control participants with and without OBT. Participants were instructed to close their eyes during the experiment for the purpose of eliminating retinal inputs. Without OBT, no V1 responses were detected in both groups of participants. With OBT, to the contrary, both stimuli caused substantial V1 responses in JMD patients, but not controls. Furthermore, we also found that the task-dependent activity in V1 LPZ became less pronounced when JMD patients opened their eyes, suggesting that task-related feedback signals can be partially suppressed by residual feedforward signals. Modality-independent V1 LPZ responses only in the task condition suggest that V1 LPZ responses reflect task-related feedback signals rather than reorganized feedforward visual inputs.

High prevalence of mutations in the EYS gene in Japanese patients with autosomal recessive retinitis pigmentosa.

PURPOSE: To screen for disease-causing mutations in the Eyes shut homolog (EYS) gene in Japanese patients with retinitis pigmentosa (RP). Methods. Blood samples were obtained from 68 RP patients and 68 controls. Genomic DNA was extracted from the blood samples and used for screening of mutations in the coding exons by direct sequencing. Each patient underwent a detailed clinical examination. RESULTS: Nine nucleotide sequence variations causing amino acid changes were observed in homozygous or heterozygous alleles in 26 patients but not in 68 controls. Seven truncating mutations were found in 21 (32.8%) of 64 patients with nonsyndromic RP composed of 23 autosomal recessive RP (arRP) and 41 sporadic cases. The most abundant mutation was p.S1653Kfs*2, which was generated by a single adenine insertion into exon 26 (c.4957dupA) and was carried by 15 patients. The mutation p.Y2935*, produced by a single nucleotide substitution (c.8805C>A) in the last exon, was carried by five patients. These two truncating mutations were probably founder mutations because each was carried by the particular haplotype. The patients with homozygous or compound heterozygous truncating mutations showed a severe decline in visual acuity, whereas those with a single truncating mutation showed a mild decline. CONCLUSIONS: One-third of Japanese patients with nonsyndromic arRP carried probable pathogenic mutations in the EYS gene, including two founder mutations. Because the genotype was correlated with the phenotype, genotyping in the EYS gene could be a valuable tool for predicting long-term prognoses of Japanese patients with arRP and thus could be useful for genetic counseling and future gene therapy.

Effects of selective-wavelength block filters on pupillary light reflex under red and blue light stimuli.

PURPOSE: To investigate at which wavelength melanopsin-containing retinal ganglion cells (mRGCs) depolarize and how they affect pupillary constriction induced by light stimulation in humans. METHODS: The pupil light reflex was evaluated for 30 normal subjects by use of an infrared pupillometer. Blue light stimulation (470 nm) and red light stimulation (635 nm) of 100 cd/m(2) were selected. Selective-wavelength block filters which can selectively remove the wavelengths 440 and 470 nm were used. Visual tests were also performed to observe the effects of the filters on visual acuity, color vision, and contrast sensitivity. RESULTS: The pupil transiently constricts and then settles toward a steady-state diameter when stimulated with the light. When the 470-nm-block filter was worn, the sustained phase of pupillary constriction, thought to be mediated by the mRGCs, was not stable but there was no effect on the initial phase of pupillary constriction under blue light stimulation. Visual acuity, color vision, and contrast sensitivity were not affected by the 470-nm-block filter. CONCLUSIONS: These results suggest that the mRGC in humans may respond to 470-nm-wavelength light at 100 cd/m(2), and there is a possibility of affecting the sustained phase of the light reflex without changing visual performance.

Reconsideration of the most appropriate criterion in the lowest classification of vision disability in Japan.

PURPOSE: To verify the current Japanese classification of vision disability in regard to visual acuity. METHODS: A questionnaire was sent to 100 ophthalmology services in Japan. Each service was asked to extract 300 of their outpatient records. From these records, patients who had a sum of corrected visual acuity in both eyes of less than or equal to 0.62 were selected for the questionnaire. The questionnaire consisted of items related to prevalence, age, sex, with or without vision-disabled certification at any grade, the corrected visual acuity of each eye and the name of any disease the subject may have had. RESULTS: Sixty-five services responded, and, of 20,235 total records reviewed, 971 patients were eligible for the questionnaire. The average age was 66.9 ± 20.0 years, and 74.6% were over 60 years old. The distribution of corrected visual acuity showed three categories. CONCLUSIONS: Our analysis indicates that a new candidate criterion for vision-disabled certification is needed for the sixth grade, which, at present is defined as, "The sum of the corrected visual acuity of both eyes is more than 0.2, but less than or equal to 0.4."

Activation in left primary visual cortex representing parafoveal visual field during reading Japanese texts.

Activation in the left primary visual cortex (V1) representing the parafoveal field during text reading has been interpreted as attentional modulation in the process of deciding saccadic target for reading ahead. Kanji words serve the main cue to decide the goal of saccades in Japanese. We aimed to determine the exact location of this modulation in the V1 and to determine whether the area of the modulation changes according to the location where the next Kanji word appears or it is fixed on a certain region in V1. Using functional magnetic resonance imaging, we determined the area in V1 representing each eccentricity on the horizontal meridian of the visual field for each participant. Then we investigated brain activation while they were reading two sets of Japanese texts that scrolled leftward as the participants. In set 1, the distance between the heads of adjacent Kanji words was about 3°. In set 2, the distance was about 5°. From the results of these experiments, we obtained activation amplitude of the area corresponding to each eccentricity. We recorded eye movements simultaneously with the acquisition of fMRI data. The maximum peak of the activation was found in the region representing about 4.5° of eccentricity on the horizontal meridian in the left V1 for each participant. The activation pattern did not essentially differ between the two text conditions, although the location of the saccades made for reading next section of the text corresponds to the head of the next Kanji word. The activation modulation during reading Japanese texts occurs in the parafoveal V1 of the left hemisphere. The attentional modulation did not change with the distance to the next goal of saccade but was fixed on the area representing about 4.5° of eccentricity.

Task-dependent V1 responses in human retinitis pigmentosa.

PURPOSE: During measurement with functional MRI (fMRI) during passive viewing, subjects with macular degeneration (MD) have a large unresponsive lesion projection zone (LPZ) in V1. fMRI responses can be evoked from the LPZ when subjects engage in a stimulus-related task. The authors report fMRI measurements on a different class of subjects, those with retinitis pigmentosa (RP), who have intact foveal vision but peripheral visual field loss. METHODS: The authors measured three RP subjects and two control subjects. fMRI was performed while the subjects viewed drifting contrast pattern stimuli. The subjects passively viewed the stimuli or performed a stimulus-related task. RESULTS: During passive viewing, the BOLD response in the posterior calcarine cortex of all RP subjects was in phase with the stimulus. A bordering, anterior LPZ could be identified by responses that were in opposite phase to the stimulus. When the RP subjects made stimulus-related judgments, however, the LPZ responses changed: the responses modulated in phase with the stimulus and task. In control subjects, the responses in a simulated V1 LPZ were unchanged between the passive and the stimulus-related judgment conditions. CONCLUSIONS: Task-dependent LPZ responses are present in RP subjects, similar to responses measured in MD subjects. The results are consistent with the hypothesis that deleting the retinal input to the LPZ unmasks preexisting extrastriate feedback signals that are present across V1. The authors discuss the implications of this hypothesis for visual therapy designed to replace the missing V1 LPZ inputs and to restore vision.

Evaluation of early state of cyanopsia with subjective color settings immediately after cataract removal surgery.

We evaluated cyanopsia by means of achromatic-point settings at several time points started from the day before intraocular lens (IOL) implantation for cataract removal surgery. We intensively measured the initial drift in color appearance; we started the measurement less than 30 min after eyepatch removal, and the measurement continued for several weeks. The shifts were mainly observed in the direction of color space that selectively varies short-wavelength-sensitive cone (S-cone) responses. The time constant of shifts in color appearance was estimated at the initial stage of cyanopsia by fitting exponential curves. The result of fitting suggests that color appearance is recalibrated during cyanopsia by some neural mechanisms with a time constant of several hours. It also became clear that the migration of the achromatic point becomes slower within approximately 12 h after eyepatch removal.

Objective perimetry using functional magnetic resonance imaging in patients with visual field loss.

In ophthalmic clinics, subjective perimetry is a standard examination method. However, for certain patients, objective perimetry is useful since it avoids the need for subjective judgments. The purpose of the present study is to demonstrate the feasibility of objective perimetry using functional magnetic resonance imaging (fMRI). fMRI was performed in 8 patients with visual field defects caused by cerebral lesions. The composite stimulus was either the combination of an expanding ring and a clockwise rotating wedge, or a contracting ring and a counter-clockwise rotating wedge. The largest radius was a 10 degrees visual angle with magnifying glasses. The cycle period for the ring and wedge components differed, enabling us to distinguish the two targets within a single time series. Data were analyzed using custom software that interprets the two stimuli and estimates visual field maps. Regions of interest (ROIs) were set covering the entirety of the occipital lobes, and the most effective visual field location for each voxel was calculated from these two response components. The visual field maps obtained with fMRI were compared with the 10-2 Humphrey visual field (HVF) program. While some divergences were observed, in most subjects the visual field defects on fMRI agreed with those on HVF. Cross-correlation coefficients between grayscale values of visual field maps obtained with fMRI and decibel values obtained with HVF were significant (P<0.05) in all subjects. fMRI in conjunction with our method is feasible for objectively and efficiently measuring the visual field of patients with visual field loss.

Two temporal channels in human V1 identified using fMRI.

Human visual sensitivity to a fairly broad class of dynamic stimuli can be modeled accurately using two temporal channels. Here, we analyze fMRI measurements of the temporal step response to spatially uniform stimuli to estimate these channels in human primary visual cortex (V1). In agreement with the psychophysical literature, the V1 fMRI temporal responses are modeled accurately as a mixture of two (transient and sustained) channels. We derive estimates of the relative contributions from these two channels at a range of eccentricities. We find that all portions of V1 contain a significant transient response. The central visual field representation includes a significant sustained response, but the amplitude of the sustained channel signal declines with eccentricity. The sustained signals may reflect the emphasis on pattern recognition and color in the central visual field; the dominant transient response in the visual periphery may reflect responses in the human visual attention system.

V1 projection zone signals in human macular degeneration depend on task, not stimulus.

We used functional magnetic resonance imaging to assess abnormal cortical signals in humans with juvenile macular degeneration (JMD). These signals have been interpreted as indicating large-scale cortical reorganization. Subjects viewed a stimulus passively or performed a task; the task was either related or unrelated to the stimulus. During passive viewing, or while performing tasks unrelated to the stimulus, there were large unresponsive V1 regions. These regions included the foveal projection zone, and we refer to them as the lesion projection zone (LPZ). In 3 JMD subjects, we observed highly significant responses in the LPZ while they performed stimulus-related judgments. In control subjects, where we presented the stimulus only within the peripheral visual field, there was no V1 response in the foveal projection zone in any condition. The difference between JMD and control responses can be explained by hypotheses that have very different implications for V1 reorganization. In controls retinal afferents carry signals indicating the presence of a uniform (zero-contrast) region of the visual field. Deletion of retinal input may 1) spur the formation of new cortical pathways that carry task-dependent signals (reorganization), or 2) unmask preexisting task-dependent cortical signals that ordinarily are suppressed by the deleted signals (no reorganization).

[Functional MRI activation in area V4 alpha during a hue arrangement test].

BACKGROUND: Recent studies of cerebral information processing have shown that area V4 alpha, the area anterior to area V4, which is known as the human color center, is also associated with color. However, our clinical study has shown that lesions associated with hue arrangement test failures are more anterior than those associated with pseudoisochromatic plate test failure. PURPOSE AND METHODS: We studied area V4 alpha, and planned two functional magnetic resonance experiments for V4 alpha activity during the hue arrangement test. The task in the first experiment was virtual simulation of the hue arrangement test. The second experiment involved a task more specific to color information processing. RESULTS: We found significant activity in area V4 alpha in healthy subjects. CONCLUSIONS: We have reported that one of our patients with a more anterior lesion excluding area V4 had dyschromatopsia, as revealed by a panel D-15 test. Our experimental data and the clinical findings suggest that area V4 alpha plays an important role in processing during the hue arrangement test.

[Analysis with magnetic resonance imaging of lesions in cerebral achromatopsia].

PURPOSE: To localize the lesions associated with cerebral achromatopsia. METHODS: We examined 20 patients with homonymous hemianopsia caused by cerebral infarction(17 men and 3 women aged 49 to 81 years; mean age, 65.1 years). Ishihara plates, standard pseudoisochromatic plates(part 2) and the panel D-15 test were used to examine color perception. Color matching tasks and color naming tasks were used to test color recognition. We tried to apply functional magnetic resonance imaging(fMRI) to lesion analysis in the brain. RESULTS: Cerebral achromatopsia was diagnosed in four patients. The analysis showed that lesions in the infracalcarine area(Brodmann's area 18 and 19) were associated with cerebral achromatopsia. Additionally, the lesions associated with failure of the panel D-15(PD-15) test were located more anterior than the lesions associated with failure of Ishihara plates. CONCLUSION: We show evidence that lesions in the anterio-ventral temporo-occipital area are associated with cerebral achromatopsia. This result is in accord with past observations(autopsy, fMRI and positron emission tomography).