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Physiological aspects of visual perception. I. Functional aspects of visual cortex.

The first part of the Bennett Lecture for 1975 is a description of the dissociation of visual perception in the macaque monkey by ablation of area 17 on the one hand, and of areas 18 and 19 on the other. Bilateral removal of area 17, with careful preservation of a great part of areas 18 and 19, and of the inferior pulvinar, resulted in loss of binocular fixation, loss of visual recognition of still objects, and loss of visuosocial behavior such as grimacing and vocalization. There remained excellent visuospatial orientation and reaching for moving peripheral visual targets. Removal of areas 18 and 19, with isolation of area 17 from the remainder of cortex, was accomplished in two animals and left intact the ability to distinguish and sort out still objects by vision, with intact fixation, and visuosocial behavior. Spatial orientation was then easily confused by movement.

Animals↗

Optical imaging of intrinsic signals as a tool to visualize the functional architecture of adult and developing visual cortex.

One of the most common principles of cortical organization is that neurons with similar response properties are clustered together in space. Thereby the environment is represented in an orderly fashion on the cortical surface in a so-called "cortical map". In primary visual cortex, for instance, neurons with similar orientation preferences are grouped together, forming the orientation preference map. Optical imaging of intrinsic signals allows to investigate the organization of such maps in vivo. Neuronal activity was measured utilizing the fact that the transition from oxy-hemoglobin to hemoglobin in active brain areas can be detected optically by recording changes in light reflectance with a high resolution CCD-camera. When using this technique to look at the exact patterning of orientation preference maps in cat visual cortex a novel principle for the organization of cortical maps was observed: orientation was not organized in parallel bands as had previously been thought but iso-orientation domains were organized radially; orientations from 0 to 180 degrees were laid out in a pinwheel-like fashion around singularities which we termed "orientation-centers". After observing pinwheel patterns in orientation preference maps in adult cat visual cortex it was also investigated how these meticulously arranged maps develop in the cortex of young kittens. Performing chronical recordings in kittens from the age of postnatal day 17 on we were able to observe how orientation maps form already during the third week of life and--under normal conditions--remain largely unchanged thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Visualization of functionally activated circuitry in the brain.

We have used a transgenic approach to visualize functionally activated neurons and their projections. The transgenic mice contain a tau-lacZ fusion gene regulated by the promoter for c-fos, an immediate early gene that is rapidly induced in neurons after functional stimulation. Constitutive expression of beta-galactosidase (beta-gal), the lacZ product, was low and in accord with previous reports of c-fos expression. However, expression of beta-gal in positive neurons was clearly in cell bodies, axons, and dendrites. Treatment of the mice with kainic acid, a strong inducer of c-fos expression, resulted in high induction of beta-gal. beta-gal was induced in the same defined populations of neurons in the brain as those that express c-fos after kainic acid induction. Furthermore, the pattern of beta-gal expression within the neurons changed over time after kainic acid treatment. Early after kainate treatment, beta-gal was found mainly in cell bodies; at later times, expression extended further along the neuronal processes. This expression pattern is consistent with induction and anterograde transport of the Fos-Tau-beta-gal protein in the neurons. To test whether a functionally activated pathway could be visualized, transgenic mice were deprived of water, which activates nuclei involved in body fluid homeostasis. beta-gal induction was traced in neurons and their processes in the lamina terminalis, in magnocellular neurons of the supraoptic and paraventricular nuclei, and in their projections to the posterior pituitary gland. This strategy allowed the mapping of an activated osmoregulatory pathway. This transgenic approach may have general application in the mapping of functionally activated circuitry in the brain.

Animals↗

Enhanced interictal responsiveness of the migraineous visual cortex to incongruent bar stimulation: a functional MRI visual activation study.

Since visual aura is usually described as expanding zigzag lines, neurones involved with the perception of line orientation may initiate this phenomenon. A visual incongruent line stimulation protocol was developed to obtain functional magnetic resonance images (fMRI) interictally in 5 female migraine patients with typical fortification spectra and in 5 normal matched controls. Activation in the visual cortex was present contralateral to the side of stimulation in 4 of 5 patients, notably in the extrastriate visual cortex. In 4 of 5 controls activation was observed in the medial and anterior orbitofrontal cortex. In one of them additional activation at the right nucleus accumbens/ventral striatum and right ventral pallidum was present. In the remaining control subject activation was present in the left primary visual cortex. The enhanced interictal reactivity of the visual cortex in migraineurs supports the hypothesis of abnormal cortical excitability as an important pathophysiological mechanism in migraine aura, though the role of specific regions of the visual cortex remains to be explored.

Adult↗

Measurement of low vision in children and infants.

The authors evaluated a preferential looking technique (Teller acuity cards) and a set of gross behavioral indicators (visual function battery) for the ability to rank visually impaired children and infants on the basis of their visual function. Fourteen older children with a diagnosis of cicatricial retinopathy of prematurity who were capable of giving Snellen acuities and a group of 31 preverbal infants with decreased vision due to a variety of causes were tested. Teller acuity card and visual function battery findings were highly correlated with each other (and with Snellen acuities in the older group); however, the Teller acuity cards provided better discrimination in the moderately visually impaired range, whereas the visual function battery was better in the severely impaired range. It is concluded that, in children and infants, visual function over the entire spectrum of low vision can be characterized by using a combination of the Teller acuity cards and the visual function battery.

Adolescent↗

[A new reading chart for simultaneous determination of reading vision and reading speed].

BACKGROUND: Reading acuity as well as reading speed are good predictors of everyday visual function. As visual acuity tests are poor predictors of the real-world function, performance-based tests, e.g., reading speed measurements, can be used for the determination of visual function. Thus, a German reading chart was developed in order to evaluate reading acuity as well as reading speed. METHODS: Print size is defined as the height of a lower case x and progresses logarithmically from one phrase to another (factor: 1.25). Reading acuity is determined in LogRAD (Reading Acuity Determination). 32 short German phrases were created, comparable concerning grammatical difficulty as well as in number (n = 14), length and position of words. The reading speed parameters measured with a stop-watch in 160 persons (aged: Phi = 21a +/- 3.8a) were calculated in words per minute (w/min). Out of the 32 phrases the 24 most similar ones were selected statistically and used for the reading charts (Radner Reading Charts). With these reading charts a reading acuity score (LogRAD-score) can be calculated considering reading errors in words of different length. Reading speed can be determined at the same time. Reading acuity (LogRAD-Score) was measured in 32 normal eyes of 16 students and compared to the angular visual acuity (LogMAR). RESULTS: The mean reading speed of the test persons was 211.8 +/- 34.1 w/min. 24 phrases fulfilled the test item criteria for the reading chart: mean +/- 0.25 x SD. The reliability analyses yielded an overall Cronbach's alpha coefficient of 0.98! The mean visual acuity measured in 32 eyes was -0.115 +/- 0.097 LogMAR and the mean reading acuity score was +0.026 +/- 0.091 LogRAD. The mean difference was +0.104 +/- 0.066 and the correlation between LogMAR and LogRAD was good (r = 0.59). CONCLUSIONS: With these reading charts it is for the first time possible to simultaneously determine reading acuity as well as reading speed in German. The high reliability of the 24 phrases and the high correlation between LogMAR and LogRAD leads us to expect a good reproducibility of the reading acuity evaluations. For the "Radner Reading Charts" we have shown that print size is the main reason for changes of reading speed.

Adolescent↗

Duration of self assessed benefit of cataract extraction: a long term study.

AIM: To investigate how long patients' improved visual function lasts after a cataract extraction. METHODS: Patients' self assessed visual function was evaluated using the Catquest questionnaire both before and 6 months after a cataract extraction. The study population consisted of 615 patients undergoing a cataract extraction during 1995-2002. A final follow up with a new questionnaire was performed in 2003, between 1 year and 8 years after surgery. RESULTS: 445 (72.4%) patients were alive at follow up and agreed to participate in the study. The number of subjects still showing improved visual function after surgery decreased with longer follow up. After 7 years, 80% had improved visual function compared with before surgery. 50% of all originally operated subjects were alive 7 years postoperatively and enjoyed better visual function than they had done before surgery. Ocular co-morbidity in the operated eye or self assessed poor visual function before surgery was significantly related to deteriorated visual function at follow up. CONCLUSION: The number of subjects who experienced improved visual function after a cataract extraction decreased over the course of time postoperatively. Presence of ocular co-morbidity was significantly related to worsened function.

Aged↗

Thalamic atrophy in infants with PVL and cerebral visual impairment.

The aim of this retrospective study was to establish the presence and severity of cerebral visual impairment in preterm infants with PVL. We also wished to establish whether abnormalities of visual function are related to brain MRI findings and more specifically not only to the involvement of optic radiations and occipital cortex but also to changes in the thalami, that are often affected in infants with PVL. Twelve infants with cystic PVL were assessed at 1 year (+2) corrected age with a battery of tests specifically designed to assess various aspects of visual function in infancy, such as ocular movements, visual acuity, visual fields and fixation shift. All infants also had a brain MRI. Eleven of the 12 had involvement of the optic radiations: all had some abnormalities of visual function and visual impairment was more severe in infants with more extensive involvement of the optic radiations. The child with normal optic radiations had normal visual function. Six of the 12 infants also had obvious signs of atrophy of the thalami and all had severe and wide-ranging abnormalities of visual function in all testing domains. Two children had equivocal atrophy of the thalami, both had some abnormalities of visual function. Four children had normal thalami and had normal visual function or only minor abnormalities on one of the visual tests. Our results suggest that the atrophy of the thalami may play an additional role in the abnormal development of visual function in infants with PVL and abnormal optic radiations.

Atrophy↗

Higher functions and plasticity in visual pathways.

A summary of the visual pathways in the brain is presented as a basis for considering abnormalities in this system. The role of the cortical associative regions in visual function is briefly delineated. A short summary of experiments describing plastic properties of the visual pathways at early age is also presented, and experiments describing neural and behavioural changes after binocular deprivation are reviewed. It is concluded that early visual deprivation leads to a profound alteration of the associative systems of the brain and that in monkeys and humans these changes are difficult to remedy later. Therefore early detection and correction of visual abnormalities is very important as well as early compensation using other forms of sensory communication.

Adult↗

Soluble guanylate cyclase is required during development for visual system function in Drosophila.

A requirement for nitric oxide (NO) in visual system development has been demonstrated in many model systems, but the role of potential downstream effector molecules has not been established. Developing Drosophila photoreceptors express an NO-sensitive soluble guanylate cyclase (sGC), whereas the optic lobe targets express NO synthase. Both of these molecules are expressed after photoreceptor outgrowth to the optic lobe, when retinal growth cones are actively selecting their postsynaptic partners. We have previously shown that inhibition of the NO-cGMP pathway in vitro leads to overgrowth of retinal axons. Here we examined flies mutant for the alpha subunit gene of the Drosophila sGC (Gcalpha1). This mutation severely reduced but did not abolish GCalpha1 protein levels and NO-stimulated sGC activity in the developing photoreceptors. Although few mutant individuals possessed a disorganized retinal projection pattern, pharmacological NOS inhibition during metamorphosis increased this disorganization in mutants to a greater degree than in the wild type. Adult mutants lacked phototactic behavior, and the off-transient component of electroretinograms was frequently absent or greatly reduced in amplitude. Normal phototaxis and off-transient amplitude were restored by heat shock-mediated Gcalpha1 expression applied during metamorphosis but not in the adult. We propose that diminished sGC activity in the visual system during development causes inappropriate or inadequate formation of first-order retinal synapses, leading to defects in visual system function and visually mediated behavior.

Animals↗

[The relationship between visual agnosia and visual pathway for perception].

We report a patient with a unique visual agnosia, who was thought to have lost visual functions except for the primary visual function. The patient was a 71-year-old woman with progressive memory loss and cerebro-cortical atrophy in MRI; her clinical diagnosis was senile dementia of Alzheimer's type. A battery of tests to detect higher visual dysfunctions was performed. First of all, we presented small dots and lines in front of the patient; the patient was able to recognize them. When a triangle, a tetragon, a cube, pieces of paper of different colors and lines of different length were presented, she was unable to recognize those objects. When pictures of her family members or filled circles of different size including small dots and lines were presented, the patient could only detect those small dots and any of lines; she could not recognize the members of her family. The cerebral blood flow was severely reduced in the occipital lobe except for the striate cortex. These data suggested that the visual function of striate cortex was preserved in this patient; the disturbance of higher visual functions was thought to be caused by the dysfunction of extra striate cortex.

Aged↗

Vision after early-onset lesions of the occipital cortex: I. Neuropsychological and psychophysical studies.

We analyzed the visual functions of two patients (MS, FJ) with bilateral lesion of the primary visual cortex, which occurred at gestational age 33 wk in MS and at postnatal month 7 in FJ. In both patients basic visual functions--visual acuity, contrast sensitivity, color, form, motion perception-are similarly preserved or modestly impaired. Functions requiring higher visual processing, particularly figure-ground segregation based on textural cues, are severely impaired. In MS, studied longitudinally, the deficits attenuated between the ages of 4.5 and 8 y, suggesting that the developing visual system can display a considerable degree of adaptive plasticity several years after the occurrence of a lesion. In FJ (age 18:9 to 20:6 y), who is more impaired, the recovery, if any, was less.

Adolescent↗

[Studies on vision mediated behavioral changes of rat with photic injury].

OBJECTIVE: To evaluate the relationship of visual function and photoreceptor cell loss, and to establish a visual function assessment system based on the observation of optokinetic behavior in rat with photic injury. METHODS: SD rats were exposed to (950 +/- 50) lux green light for 3 hours, 12 hours and 24 hours respectively after 24-hour dark adaptation. Then 24-hour dark recovery was followed by 48-hour observation before the eyes were enucleated. Frozen sections were obtained. Slides were stained by HE and rhodopsin immunofluorescent stainings. Vision mediated disturbance of consciousness and pre-pulse response were used to assess the visual function. Optokinetic behavior test was conducted 2 days before and after photic injury. Average velocity of motion were analyzed. RESULTS: Vision mediated disturbance of consciousness response are gradually weakened; while pre-pulse response is reinforced as the photic injury time increases. The relationship of optokinetic behavior and rat visual function is statistically significant. Optokinetic behavior test shows the average velocity of motion gradually decreases as the injury is aggravated. CONCLUSIONS: Longer light exposure time leads to increased photoreceptor injury, which in turn, causes decrease of visual function in SD rat. Optokinetic behavior test, represented by average velocity of motion, is correlated with rat visual function. Thus, optokinetic behavior test can be used to assess the visual function of SD rat quantitatively.

Animals↗

Visual dysfunction in workers exposed to a mixture of organic solvents.

The aim of this study was to investigate the relationship between the workers occupationally exposed to a mixture of organic solvents and their visual functions. Here the visual functions included color vision (CV), visual contrast sensitivity (CS) and visual evoked potentials (VEP). Test subjects were 182 workers at 53 furniture factories in the same industrial area of Japan. As control, a group consisted of 96 workers without exposure to any organic solvent was also tested. Exposure assessments were made both by the environmental concentration and biological monitoring. CV and CS tests were carried out for all the subjects. VEP was measured for 21 exposed subjects who were considered to have impaired CV and CS. In the results, the color confusion index (CCI) values of the exposed subjects were significantly higher than that of the age-matched controls (P<0.01). Their CS values were significantly lower than those in the controls at spatial frequencies of 6 and 12 cycles per degree (cpd) (P<0.01 and <0.05, respectively). A significant correlation between the concentration of urinary methylhippuric acid and contrast sensitivity was found by a multiple regression analysis (P<0.05). CCI showed a negative correlation at all spatial frequencies of CS in a simple regression analysis, no abnormal data were found by the VEP test in the exposed subjects who were found to have impaired CV and CS. The results suppose that a low concentration of the mixed organic solvents might affect the retina and optic nerve. However, it needs to be further researched if such an impact affects the Brodmann's areas of visual cortex in the brain.

Adult↗

A protocol for measuring ophthalmologic morbidity and recovery after cranial base surgery.

Patients with cranial base tumors often have impairment in visual function, either due to the pathologic process itself or as a result of surgical treatment of the lesion. We conducted a pilot study in which we performed ophthalmologic evaluations on patients before and after cranial base surgery. The results of the study were used to develop a protocol and reporting form for longitudinal assessment of visual function in these patients. Use of the protocol and reporting form for the past 2(1/2) years has shown that they are easy for physicians to use and that the results provide a representative evaluation of the patient's ability to function visually in everyday life. The authors propose implementation of the protocol and reporting form as a means of collecting data for further research into visual function in patients with cranial base tumors.

Journal Article↗

Relationship between vision impairment and eye disease to vision-specific quality of life and function in rural India: the Aravind Comprehensive Eye Survey.

PURPOSE: To determine the impact of vision impairment and eye diseases on vision-specific quality of life and visual function in an older population of rural southern India. METHODS: Presenting and best-corrected visual acuity and burden of eye diseases were determined in a population aged 40 years and older, identified through a random cluster sampling strategy from 50 villages of rural south India. A questionnaire validated previously for use in this population was used to ascertain quality of life and visual function. Visual acuity measurements were obtained with illiterate E Early Treatment Diabetic Retinopathy Study (ETDRS) charts. Cataract was graded and defined based on the Lens Opacities Classification System (LOCS) III. Macular degeneration was defined based on the classification system proposed by the International ARM Epidemiologic Study Group. Glaucoma was defined based on results of clinical examinations including optic disc and visual fields. Analyses were performed to explore the relationship of overall and subscale quality-of-life and visual function scores with presenting acuity in the better-seeing eye, specific eye diseases, and demographic variables. RESULTS: Information on quality of life and visual function were available for 5119 (99.4%) of 5150 study subjects. The mean presenting visual acuity in the better eye was 0.76 +/- 0.53 logMAR (logarithm of the minimum angle of resolution) units. Age, education, occupation, presenting acuity in the better eye, and presence of a cataract, glaucoma, or refractive error were independently associated with overall quality-of-life and vision function scores. After adjustment for demographic variables and ocular disease, persons with vision impairment or bilateral blindness based on presenting visual acuity had lower scores across all domains of quality of life and vision function. Scores for subscales of quality-of-life and vision function domains were significantly lower among those with age-related cataract and glaucoma compared with persons without those eye diseases. CONCLUSIONS: Presenting vision in the better eye was associated with quality of life and vision function in this older population of rural south India. Subjects with glaucoma and age-related cataract had an associated decrease in quality of life and vision function, independent of presenting visual acuity in the better eye.

Adult↗

Management of sight-threatening optic nerve sheath meningioma with fractionated stereotactic radiotherapy.

BACKGROUND: Previous management of optic nerve sheath meningioma included conservative observation, surgery, radiosurgery and conventional radiotherapy. All carried significant risk, either of visual loss or damage to adjacent structures. Fractionated stereotactic radiotherapy appears to have few side-effects and may preserve or improve vision. To date only three groups have published their experience with this modality. METHODS: A retrospective review of patients with optic nerve sheath meningioma treated with stereotactic radiotherapy in an academic complex was conducted. Patients with greater than 18 months follow up and no previous related surgery were eligible for inclusion. Patients received an average of 43.5 Gy to the tumour in 26 fractions. Case records from the treating institutions as well as those of the referring ophthalmologist were analysed. The limited literature on the subject was reviewed in order to draw conclusions relevant to contemporary patient management. RESULTS: Four patients had undergone follow up for over 18 months. Prior to treatment all had exhibited progressive loss of visual function. In all cases visual function remained stable or improved at the last assessment. Side-effects included radiologically detected cerebral changes in one patient and transient hair loss in one patient. CONCLUSIONS: This treatment modality represents a promising refinement of previous treatment options. It may be offered to patients who demonstrate progressive loss of visual function caused by optic nerve sheath meningioma. It offers significant advantages over other currently available therapeutic options but its use should be tempered by the knowledge that long-term side-effects are yet to be determined.

Adult↗