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PubMed2002

[Establishment of the concept of new clinical entities--complete and incomplete form of congenital stationary night blindness].

I summarized our long-term study to prove that the complete and incomplete types of congenital stationary night blindness (CSNB) are different clinical entities and that the latter is a newly identified disease which has never been reported in the past. CSNB with normal fundi and negative electroretinogram (ERG) showing selective reduction of the b-wave was previously known as the "Schubert-Bornschein type". For the sake of convenience, we classified the disease into two types according to the absence or the presence of rod function: complete CSNB and incomplete CSNB. The hereditary mode of the former is X-linked recessive and autosomal recessive, while that of the latter is X-linked recessive. They are never found together in a single family. We found several additional differences between the two types, including ERG oscillatory potentials, cone mediated ERG, and refractive errors, all leading us to hypothesize that the two types are not variants of a single disease but are the sum of two different clinical entities. Our hypothesis has recently been proven true by molecular genetical analysis. Namely, the mutated gene in X-linked recessive complete CSNB was found in the nyctalopin (NYX) gene, while that in incomplete CSNB was found in the calcium channel (CANCA1F) gene which encodes the retina-specific calcium channel alpha 1-subunit. These results proved that complete and incomplete CSNB are different clinical entities and that the latter is the first disease of the eye which discloses mutation of this region. We classified 90 patients to include 49 complete and 41 incomplete types. Fifteen incomplete CSNB patients underwent gene analysis and they all showed mutation of the CACNA1F gene. We also examined for gene mutation in several patients who had progressive retinal disease and negative ERG and found two siblings with CANA1F gene mutation. This finding indicates that the mutation of the CACNA1F gene can also cause progressive retinal disease in addition to incomplete CSNB. Gene analysis of 11 patients with complete CSNB was performed and 6 revealed mutation of the NYX gene. The remaining 5 patients showed neither NYX nor CACNA1F gene mutation, suggesting they are of autosomal recessive complete CSNB where gene mutation has not been identified. The comparison of our phenotype and genotype diagnosis indicated that a precise ERG analysis can provide correct differentiation between complete and incomplete types. Other clinical findings include moderately low visual acuity in both types, high or moderate myopia in complete CSNB, and wide distribution from myopia to hyperopia in incomplete CSNB. Pathophysiology studies using clinical patients and animal models suggested that complete CSNB has a complete defect of the ON-bipolar cells or their synapses in the rod and cone visual pathways, leaving the OFF pathway intact (OFF-retina). On the other hand, the incomplete CSNB has an incomplete defect of the ON and OFF bipolar cells or their synapses in the rod and cone visual pathways. The macular function is relatively well preserved in both types, which was shown by focal macular ERG. The incomplete CSNB patients seldom complain of night blindness, which causes us to overlook this disease because we then tend not to perform ERG testing. This disease is not so rare and clinicians should be more aware of its existence. The incomplete CSNB is a new hereditary retinal disease detected by Japanese investigators just like the Oguchi disease, and it has much unknown pathophysiology which needs to be identified in the future. Since the namings of complete and incomplete CSNB may be misunderstood as indicating functional classification of one disease, it has been proposed internationally to change the name "complete type" to CSNB1 and that of "incomplete type" to CSNB2.

Humans↗

PubMed2000

Human development of perceptual organization.

Two relevant dimensions are revealed within which developmental patterns of perceptual organization might be investigated. Within the local-integrative dimension, employing a contour integration task, we found indications that spatial integration develops slowly. We also found reduced contextual modulation of a local target in children employing the Ebbinghaus illusion. Within the action-perception dimension, we hypothesize a relatively slow development of the perceptual system (mediated by the ventral visual stream), as compared to the development of the action system (mediated by the dorsal visual stream). Taken together, the data indicate that long-range neuronal connectivity supporting perceptual organization in the posterior pole of the brain, and in the ventral visual pathway is not fully developed in young children.

Adolescent↗

PubMed2005

Dynamic properties of thalamic neurons for vision.

A striking property of neurons in the lateral geniculate nucleus (LGN) of the thalamus is the ability to dynamically filter and transform the temporal structure of their retinal spike input. In particular, LGN neurons respond to visual stimuli with either burst spike responses or tonic spike responses. While much is known from in vitro studies about the cellular mechanisms that underlie burst and tonic spikes, relatively little is known about the sensory stimuli that evoke these two categories of spikes. This review examines recent progress that has been made towards understanding the spatiotemporal properties of visual stimuli that evoke burst and tonic spikes. Using white-noise stimuli and reverse-correlation analysis, results show that burst and tonic spikes carry similar, but distinct, information to cortex. Compared to tonic spikes, burst spikes (1) occur with a shorter latency between stimulus and response, (2) have a greater dependence on stimuli with transitions from suppressive to preferred states, and (3) prefer stimuli that provide increased drive to the receptive field center and even greater increased drive to the receptive field surround. These results are discussed with an emphasis placed on relating the cellular constraints for burst and tonic activity with the functional properties of the early visual pathway during sensory processing.

Action Potentials↗

PubMed1981

Auditory-visual synesthesia: sound-induced photisms.

Nine patients with visual loss due to lesions of the optic nerve or chiasm experienced photisms induced by sound. Descriptions of these varied from simple flashes of white light to complicated colorful hallucinations likened to a flame, a petal of oscillating lines, a kaleidoscope, or an ameba; they always appeared within a defective portion of the visual field as demonstrated by perimetry. The provoking sounds were usually those of normal daily life, ranged from soft to loud, and always seemed to be heard by the ear ipsilateral to the eye in which the photism was seen. Sound-induced photisms occurred under circumstances that would promote a startle reaction to sound, and each patient was startled when the photisms occurred. Visual evoked responses demonstrated partial deafferentation of the eye in which photisms were seen in seven patients tested. The phenomenon may occur when the patient with a partially deafferent anterior visual pathway is startled by sound.

Adult↗

PubMed1985

Pattern-reversal visual evoked potentials in rabbits are resistant to occlusion of the carotid artery.

Contrast (pattern-reversal) visual evoked potentials (VEPs) were examined in the awake rabbit to test the possibility that carotid occlusion would disrupt sensory transmission in the visual pathways. Rabbits were operated to ligate one carotid and to chronically transplant another one into a skin flap. VEPs to checkerboard stimuli reversing with a rate of 2/s were recorded from the visual cortex. No significant changes in latency, amplitude and waveshape of VEPs were noted after 3-30 min of carotid occlusion. Apparently, blood flow from the basilar system can be easily shunted via the circle of Willis to the territory of the internal carotid.

Animals↗

PubMed1994

The cerebral activity related to the visual perception of forward motion in depth.

We have used the technique of PET to chart the areas of human cerebral cortex specifically responsive to an optical flow stimulus simulating forward motion in depth over a flat horizontal surface. The optical flow display contained about 2000 dots accelerating in radial directions away from the focus of expansion, which subjects fixated at the centre of the display monitor. Dots remained of constant size, but their density decreased from the horizon, lying across the middle of the screen, to the foreground at the lower screen margin; the top half of the display was void. For the control stimulus the dot motions were randomized, removing any sensation of motion in depth and diminishing the impression of a flat terrain. Comparison of the regional cerebral blood flow (rCBF) elicited by the optical flow and control stimuli was thus intended to reveal any area selectively responsive to the radial velocity field that is characteristic of optical flow in its simplest natural form. Six subjects were scanned, and analysed as a group. Four subjects were analysed as individuals, their PET data being co-registered with MRIs of the cerebrum to localize rCBF changes to individual gyri and sulci. There were three main areas of activation associated with optical flow: the dorsal cuneus (area V3) and the latero-posterior precuneus (or superior parietal lobe) in the right hemisphere, and the occipito-temporal ventral surface, in the region of the fusiform gyrus, in both hemispheres. There was no significant activation of V1/V2, nor of V5. These results show that higher stages of motion take place in both the 'dorsal' and 'ventral' visual pathways, as these are commonly conceived, and that both may be fed by area V3. The information potentially derivable from optical flow concerns the direction of heading, and the layout of the visual environment, a form of three-dimensional structure-from-motion. The perceptual division of labour between the various activated areas cannot be directly inferred, though it is a reasonable supposition that the parietal activation reflects the utility of optic flow for guiding self-motion.

Adult↗

PubMed1989

Value of hyperventilation in pattern-reversal visual evoked potentials.

The effects of a standard 3 minutes' hyperventilation on the full-field pattern-reversal visual evoked potential (VEP) were studied in 33 normal subjects, 30 definite multiple sclerosis patients and in twenty-five patients with abnormal VEPs due to either tumourous compression of the anterior visual pathways or optic atrophy of other origin. Significantly greater reductions in P100 latency occurred in multiple sclerosis patients in comparison with controls (p less than 0.05). This change appeared to be specific for demyelinative type of lesion, for it was not found in cases with other types of pathology. Hyperventilation also increased the sensitivity of visual pathway impairment detection in multiple sclerosis.

Adult↗

PubMed1992

Nonselective loss of contrast sensitivity in visual system testing in early type I diabetes.

OBJECTIVE: Psychophysical methods in patients with diabetes mellitus reveal deficits of central or foveal vision. Our aim was to evaluate the contrast-sensitivity thresholds in 24 insulin-dependent (type I) diabetic patients with a short disease duration and without retinopathy, taking into account metabolic control. RESEARCH DESIGN AND METHODS: The control group consisted of age-matched nondiabetic subjects. None had visual or systemic symptoms. Contrast sensitivity measured at eight different spatial frequencies to sinusoidal bar patterns of 0.6-12.2 cycles/deg can detect functional defects in the spatially sensitive retinal ganglion cells or in higher visual pathways. We performed two different temporal types of contrast-sensitivity testing, dynamic (8 Hz) and static (0 Hz). RESULTS: Significant losses with dynamic contrast-sensitivity test at all but the highest spatial frequencies (i.e., 12.2 cycles/deg) were shown, whereas there was significant attenuation of contrast sensitivity at five spatial frequencies (1.0, 1.4, 2.2, 7.1, and 9.6 cycles/deg) in the static mode. Grating losses (less than 2SD of control means) of contrast sensitivity were found in 33.3% (dynamic) and in 72.9% (static) of eyes of diabetic patients. HbA1c values were positively correlated at variable spatial frequencies (1.0, 1.4, and 2.2 cycles/deg for dynamic test and 0.6, 1.0, 1.4, 2.2, 4.8, and 7.1 cycles/deg for static test). CONCLUSIONS: Our results suggest an early, generally nonselective neuronal damage of visual pathways that occurs before the onset of clinically detectable retinopathy. The visual deficit may be related directly to the effects of diabetes; repetitive minor hypoglycemic insults may contribute more than a marked hyperglycemic condition to the mechanisms underlying physiological changes along the optic nerve.

Adult↗

PubMed2001

Sexual differences and effect of photoperiod on melatonin receptor in avian brain.

Several data suggest that melatonin may influence avian reproduction by acting at the level of the hypothalamic-hypophisial-gonadal axis, and/or on neural circuits controlling reproductive behaviours. The action of melatonin is exerted through specific receptors whose distribution and pharmacological properties have been extensively investigated. This review will focus on the distribution, sexual dimorphism, and dependence upon the photoperiod of melatonin binding sites in avian species with a special emphasis on Japanese quail. Melatonin receptors are widely distributed in avian brain. They are mostly present in the visual pathways of all the investigated species and in the song controlling nuclei of oscine birds. Sexual dimorphism of melatonin binding sites (higher density in males than in females) was detected in some telencephalic nuclei of songbirds, in the visual pathways, and in the preoptic area of quail. The last region plays a key role in the activation of male quail copulatory behaviour and it hosts a large population of gonadotropin-releasing hormone-containing neurons. Sexual dimorphism of melatonin-binding sites in the above-mentioned regions suggests a differential role for this hormone in the modulation of visual perception, gonadotropin production, and seasonally activated behaviours in male and female quail. Further studies are necessary to understand interrelationships among photic cues, gonadal steroids, density, and sexually dimorphic distribution of melatonin receptors.

Animals↗

PubMed1977

Effects of subcortical lesions on visual intensity discriminations in rats.

The role of several subcortical structures in visual intensity discrimination was examined by comparing the effects of localized lesions on a variety of intensity discriminations. In Experiment 1 light avoidance was unimpaired after lesions of the ventral lateral geniculate nucleus (LGNv), nucleus lateralis posterior (TLP), nucleus posterior of Gurdijian (NPG), dorsal pretectum (PTd), and ventral pretectum (PTv). The LGNv, TLP, NPG and PTv, but not the PTd, groups were impaired on a simultaneous black versus white (BW) discrimination in Experiment 2. None of these groups was impaired on a horizontal versus vertical discrimination (HV). The TLP group showed a transient impairment on a successive light versus dark discrimination, not present with the LGNv and NPG groups (Experiment 3). In Experiment 4 all three groups were impaired on a successive BW discrimination. In Experiment 5 rats with LGNv lesions but not with TLP lesions had elevated relative brightness thresholds. Both groups had normal absolute thresholds. The results are related to the possibility that information about intensity and pattern is coded in separate visual pathways.

Animals↗

PubMed1998

Distribution of GABA receptor rho subunit transcripts in the rat brain.

The gamma-aminobutyric acid (GABA) receptor rho subunits recently cloned from rat and human retina are thought to form GABA receptor channels belonging to a pharmacologically distinct receptor class, termed GABA(C). In this work we have examined the distribution of rho1, rho2 and rho3 subunits, and found expression of all three transcripts in several regions of the rat nervous system. In situ hybridization revealed expression of rho2 in the adult rat retina and some other parts of the visual pathways. A high local rho2 expression was seen in the superficial grey layer of the superior colliculus, and in the dorsal lateral geniculate nucleus. Expression was also detected in the 6th layer of visual cortex and in the CA1 pyramidal cell layer of hippocampus. With reverse transcriptase-polymerase chain reaction, expression of rho1 was mainly seen in the adult rat retina and dorsal root ganglia, as well as, at a significantly lower level, in the superior colliculus, hippocampus, brain stem, thalamus, postnatal day 8 (P8) superior colliculus and P8 hippocampus. Expression pattern of rho3 mRNA was clearly different from that of rho1 and rho2, being strongest in the hippocampus, and significantly lower in the retina, dorsal root ganglia and cortex. No rho3 expression was observed in adult or P8 superior colliculus or in P8 hippocampus. The present results clearly demonstrate that expression of GABA receptor rho subunits is not restricted to the retina, but significant expression can also be detected in many other brain regions, especially in those belonging to the visual pathways. The expression pattern of the rho subunits may be helpful in solving the functional significance of the receptors formed from these subunits.

Animals↗

PubMed2006

[Significance of the cognitive context in formation of unconscious visual sets].

The experimental evidence that the cognitive set shifting in healthy humans depends on the context of cognitive performance is discussed. Lability/rigidity of the experimentally formed unconscious visual set is largely determined by the type of additional task ("what?" or "where?", i. e., stimulus recognition or spatial localization, respectively) introduced into the context of the experiment. It is suggested that the acquired set more readily shifts to a new one more adequate to modified conditions in case of alternation of the ventral and dorsal visual pathways involved in the information processing in the context of cognitive performance.

Brain↗

PubMed1985

Spatiotemporal responses of the visual system in demyelinating diseases.

Previous studies have shown that, in patients with lesions of the visual pathway, contrast sensitivity (CS) measured with stationary sine-wave gratings can demonstrate deficits, that is, anomalies in pattern detection. The purpose of this study was to investigate whether temporal processing can be affected in demyelinating lesions of the visual pathway. CS was measured for eight spatial frequencies (SF), using stationary and temporally modulated stimuli in a group of 10 patients with multiple sclerosis or optic neuritis. A control group was composed of 48 normal eyes. With stationary stimuli, CS losses were found in 17 eyes of patients; 11 of these eyes were 'unaffected'. The importance of the CS measurements in detecting early subclinical visual damage is emphasized. The effect of temporal modulation in patients with CS deficits was different from that observed in normals: CS deficits were modified by temporal variation in three distinct manners. In 7 eyes (type 1 effect), temporal modulation reduced the deficit at all SFs. In type 2 (5 eyes), the effect was reversed at low and high SFs: the deficit was reduced at low SFs (below 2-3 cycles/deg) and aggravated at high SFs. In type 3 (4 eyes), CS deficit was aggravated over most SFs. Thus these patients exhibited anomalies of the spatiotemporal responses which could not be predicted by the CS to stationary stimuli. Some theoretical models of spatiotemporal processing proposed in normal vision might account for our results. Possible explanations of these findings are proposed and discussed.

Adolescent↗

PubMed1987

[Evoked potentials in intracranial operations: current status and our experiences].

Intraoperative neuromonitoring, especially evoked potential monitoring, has gained interest in recent years for both the anesthesiologist evaluating cerebral function and the neurosurgeon wishing to avoid neuronal lesions during intracranial operations. Before evoked potential monitoring can be introduced as a routine method of intraoperative management, experience with this method particularly in intensive care units, is imperative. We recorded evoked potentials with the Compact Four (Nicolet) and Basis 8000 (Schwarzer Picker International) computer systems. Preoperative derivations should be done with the same apparatus used intraoperatively and parameters of peri- and intraoperative derivations should not be changed. The patient's head must be fixed in a Mayfield clamp in order to avoid artefacts during trepanation. The possible artefacts due to apparatus, patient, or anesthesia are summarized in the tables. The derivations of evoked potentials should be supervised by a person who is not involved in the anesthesia or the surgical procedure; this condition may change in the future with full automatization of the recording technique and alarms. Good communication between surgeon, anesthesiologist, and neurophysiological assistant is a prerequisite. The modality is chosen in accordance with the affected neuronal system: visual-evoked potential (VEP) monitoring in the management of processes affecting the visual pathway, brain stem auditory-(BAER) and somatosensory-evoked potential (SSEP) monitoring in lesions affecting these pathways, in particular space-occupying lesions of the posterior fossa. VEP monitoring may be useful, but we observed alterations of the responses without changes in the level of anesthesia or manipulation of the visual pathways. In space-occupying processes of the cerebellopontine angle, BAER could not be developed in nearly all cases because the large underlying tumor had caused the disappearance of waves II-V. In these cases SSEP monitoring could be carried out. Despite these difficulties, evoked potential monitoring seems useful. We believe, however, that it is not routinely used in operating rooms at present because alterations of the responses can be due to different causes; for the neurosurgeon, the problem as to which interdependent degrees of alteration in evoked potentials are related to neuronal disturbances remains unsolved.

Brain↗

PubMed1989

Reduction in [3H]glutamate binding in the visual cortex after unilateral orbital enucleation.

Glutamate is a major neurotransmitter in the rat visual system. The effect of lesion-induced functional deficit on [3H]glutamate binding sites within anatomical components of the visual pathway has been examined using quantitative autoradiography. In the same animals, the magnitude and extent of the functional deficit was assessed with quantitative [14C]-2-deoxyglucose autoradiography. At 24 h after orbital enucleation, significant reductions (approx. 25%) in glutamate binding were present throughout the visual cortex but there were no significant alterations in glutamate binding in the two principal projections of the retina, the superior colliculus or lateral geniculate body. Function-related glucose use was significantly reduced throughout the visual pathway after orbital enucleation. Thus, alterations in the number of glutamate binding sites occur in some, but not all, of the regions in a polysynaptic pathway in which activity is altered.

Animals↗

PubMed2005

AAV2-mediated ocular gene therapy for infantile neuronal ceroid lipofuscinosis.

Infantile neuronal ceroid lipofuscinosis (INCL) is a neurodegenerative disorder caused by mutations in the gene encoding the lysosomal enzyme palmitoyl protein thioesterase-1 (PPT1). The earliest clinical sign in INCL is blindness, followed by seizures, cognitive deficits, and early death. Little is known about the progression of the visual deficits in INCL. Here we characterize the progressive retinal dysfunction and examine the efficacy of AAV2-mediated ocular gene therapy in the murine model of INCL. Significant decreases in both mixed rod/cone and pure cone electroretinographic amplitudes were observed at as early as 2 months of age. Intravitreal injection of AAV2-PPT1 increased enzyme levels in the eye to greater than normal levels. The increased PPT1 activity correlated with improvements in the histological abnormalities as well as both mixed rod/cone and pure cone functions. We also demonstrated that palmitoyl protein thioesterase-1 activity was detected in the brain following intravitreal injection. The brain activity is likely due to anterograde axonal transport along the optic tracts. Interestingly, the degree of neurodegeneration throughout the visual pathways of the brain was greatly reduced in AAV-treated INCL mice. Therefore, intravitreal AAV-mediated gene therapy has direct benefits to the eye and to distal sites in the brain along the visual pathways.

Animals↗

PubMed1991

Ratios of template responses as the basis of semivision.

The template model starts with a layer of receptors that in the case of vision are leaky detectors or counters of photons. In many animals, the ratio of the responses of a few spectral types is the basis of colour vision irrespective of intensity. Ratios of template responses are now introduced as the basis of form discrimination. In insects, the second-order neurons on the visual pathway appear to detect temporal contrast at the spatial resolution of the retina. At the next level, in the optic medulla, we find a large number of small local neurons in a column on each visual axis. The template theory is a hypothesis about how the above system functions. All possible combinations of positive, indeterminate or negative temporal contrast are considered, at two adjacent visual axes at two successive instants, giving 81 possible local templates. These templates are therefore phasic detectors of all the possible spatiotemporal contrast combinations. Some of the template responses indicate polarity of edge, flicker, or direction of motion and other abstracted features of the stimulus pattern with the maximum spatial and temporal resolution. The ratios of numbers of template responses, in higher fields at a higher level, yield quantitative measures of the qualities of edges independently of the number of edges, but taking ratios causes a corresponding loss of the spatiotemporal resolution and the pattern within each field. Templates respond to transients without computation, are readily modified or selected in evolution and can be simulated in artificial vision.

Animals↗

PubMed2006

[Is it possible to compensate for visual field defects?].

Is it possible for a driver to compensate for visual field defects by skill along with eye and head movements? Monocular field defects with a normal second eye are no problem, because a normal binocular visual field is adequate for all areas of traffic. A total bitemporal hemianopia creates a special situation, because the patient loses a three-dimensional space behind a vertical line through the point of fixation. He may have no binocular visual field. In this case the ability to participate in certain traffic situations may be limited with reduced risk profile. A real problem is posed by defects in the binocular visual field, e.g., due to lesions of the suprachiasmal visual pathway or due to ocular diseases causing damage to both eyes (e.g., glaucoma, diabetic retinopathy, etc.). Such defects usually cannot be compensated for, neither by skill nor by eye or head movements. Saccadic eye movement training and other procedures are only of limited help. These procedures may provide some compensation for daily use; a complete restoration of the ability to participate in traffic is not possible. Rare exceptions may be patients with damage to the visual pathway acquired peri- or postnatally or in early childhood when there is still enough plasticity in the visual system to develop mechanisms of compensation by completely changing the system of eye and head movements.

Automobile Driving↗