Satoshi Nakadomari

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).

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.

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.

Phakomatous choristoma of the eyelid: Immunohistochemical observation

This article reports the first case of phakomatous choristoma of the eyelid in Japan. The tumor occurred in a 2-week-old boy and was located in the left lower lid near the inner canthus. An immunohistochemical study of this rare, congenital tumor was performed. The immunohistochemical analysis revealed that the epithelial cells of this tumor showed positive staining for vimentin, S-100 protein, and neuron-specific enolase, while they had no immunoreactivity for cytokeratin, glial fibrillary acidic protein, epithelial membrane antigen, or a macrophage marker. Both the epithelial cells and the central contents of the islands in this tumor showed positive staining with anti-human alpha crystallin monoclonal mouse IgG. These results strongly indicated that a phakomatous choristoma was of a lenticular origin.

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.

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.

Lack of photophobia associated with bilateral ventral occipital lesion

Keywords Photophobia Bilateral ventral occipitalcortex Brightness Cerebral achromatopsiaBackgroundPhotophobia is a negative reaction to light, a ‘dazzling’ thatcauses temporary discomfort and/or decline in visualfunction. In healthy individuals, transient photophobiaoccurs in response to either bright light or glare and mayserve as a protective function. In patients, chronic orpathological photophobia may occur, persisting in even avery dim light. Many factors are known to cause patho-logical photophobia, but the neural mechanisms areunknown. Here, we report a pathology of the opposite type:three patients with total lack of photophobia resulting frombilateral lesions in the ventral occipital lobe. These caseshighlight the important role the ventral occipital cortexplays in photophobia.Case reportsThree patients had large lesions in the bilateral ventraloccipital lobe with cerebral infarction (Fig. 1a–c). Fundu-scopic examination, which elicits a photophobic reaction inhealthy individuals, did not produce any reaction in thesepatients. Hence, we asked the patients whether any brightlight, including the sun, caused an aversive reaction. Thepatients said that after their brain infarction they couldview the sun directly without any photophobia (thoughthey avoided doing so because they knew it was harmful).We used a simple qualitative observation to evaluatephotophobia [1]. After exposing each patient’s eyesvia indirect ophthalmoscopy with bright-intensity light(1,592 cd/m

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(Brodmanns 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).

Retinex processing from the fMRI study on V4: artistic research of colored picture using functional MRI

Artists can imagine 2 kinds of coloured scenes with no recognizable objects. One is the abstract picture such as colour Mondrian, which includes geometric pattern: rectangles, circles and crosses. Another is the decorative texture such as Japanese traditional cloud pattern which is colour camouflage pattern and does not include geometric pattern. We created these 2 kinds of colour dot pattern stimuli composed of 4 iso-luminance colours and the same area and an achromatic version. These functional magnetic resonance imaging stimuli reveal multiple colour-sensitive areas in human ventral occipitotemporal cortex. The results showed that area V4 is highly activated by the stimulus of the abstract picture such as rectangle pattern and spiral but little activated by the stimulus of the decorative texture such as random colour dot picture and cloud pattern. We suggest V4 is activated by figures composed of colour dots with eye-like shape such as disks, crosses, gratings, spirals, and windmill-like figures, and V4 has low response to the camouflage figure in which colour dots do not include eye-like shapes.

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.