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[Visual cortex in the Tolosa-Hunt syndrome. Functional imaging for the detection of a psychogenic disorder--a case report].

Besides painful ophthalmoplegia, patients suffering from Tolosa-Hunt syndrome often present increasing loss of visual perception. The impairment of the optic nerve leads to a delay of the VEP (visual evoked potentials) responses. Using the method of magnetic resonance imaging (MRI), some patients present unspecific alterations in the vicinity of the optic nerve. However, both methods (VEP and MRI) are unsuitable to assess the effect of an impaired optic nerve function on neuronal processing in the visual cortex. We report one patient suffering from Tolosa-Hunt syndrome affecting the optic nerve. We used fMRI (functional magnetic resonance imaging) to show how this impairment of the optic nerve alters cortical processing of visual information. The activity of the unaffected visual cortex was bilaterally reduced when compared to healthy volunteers but greater that obtained from patients suffering from bilateral occipital infarction. Our results offer new opportunities to assess the efficiency of therapy in patients with increasing loss of visual perception due to the Tolosa-Hunt syndrome. Further studies are necessary to investigate, whether fMRI also provides the possibility to assess the efficiency of drug therapy on optic nerve function.

Humans↗

Early 'visual' cortex activation correlates with superior verbal memory performance in the blind.

The visual cortex may be more modifiable than previously considered. Using functional magnetic resonance imaging (fMRI) in ten congenitally blind human participants, we found robust occipital activation during a verbal-memory task (in the absence of any sensory input), as well as during verb generation and Braille reading. We also found evidence for reorganization and specialization of the occipital cortex, along the anterior-posterior axis. Whereas anterior regions showed preference for Braille, posterior regions (including V1) showed preference for verbal-memory and verb generation (which both require memory of verbal material). No such occipital activation was found in sighted subjects. This difference between the groups was mirrored by superior performance of the blind in various verbal-memory tasks. Moreover, the magnitude of V1 activation during the verbal-memory condition was highly correlated with the blind individual's abilities in a variety of verbal-memory tests, suggesting that the additional occipital activation may have a functional role.

Acoustic Stimulation↗

Co-regulation of long-term potentiation and experience-dependent synaptic plasticity in visual cortex by age and experience.

Long-term potentiation (LTP) is a lasting enhancement of excitatory synaptic transmission that follows specific patterns of electrical stimulation. Although the mechanism of LTP has been intensively studied, particularly in the hippocampus, its significance for normal brain function remains unproven. It has been proposed that LTP-like mechanisms may contribute to naturally occurring, experience-dependent synaptic modifications in the visual cortex. The formation of normal binocular connections within the visual cortex requires simultaneous input from both eyes during a postnatal critical period that can be delayed by rearing animals in complete darkness. To explore the role of LTP in this experience-dependent maturation process, we induced LTP in visual cortical slices taken at different ages from light-reared and dark-reared rats. Susceptibility to LTP coincides with the critical period and, like the critical period, can be prolonged by rearing animals in darkness. These findings support the hypothesis that LTP reflects a normal mechanism of experience-dependent synaptic modification in the developing mammalian brain.

Aging↗

Histochemical evidence for a catecholaminergic (presumably dopaminergic) projection from the ventral mesencephalic tegmentum to visual cortex in the cat.

An histochemical technique combining the retrograde transport of horseradish peroxidase (HRP) and catecholamine histofluorescence was used to identify those neurons of the cat's mesencephalic ventromedial tegmentum (VMT) which project to visual cortex. In a region corresponding to the ventral tegmental area-A10 nucleus we identified a group of fluorescent cells which were retrogradely labeled by HRP injections into visual cortex. It is suggested that these cells belong to a hitherto unknown, posterior part of the mesocortical dopaminergic system.

Afferent Pathways↗

Learning to see: experience and attention in primary visual cortex.

The response properties of neurons in primary sensory cortices remain malleable throughout life. The existence of such plasticity, and the characteristics of a form of implicit learning known as perceptual learning, suggest that changes in primary sensory cortex may mediate learning. We explored whether modification of the functional properties of primary visual cortex (V1) accompanies perceptual learning. Basic receptive field properties, such as location, size and orientation selectivity, were unaffected by perceptual training, and visual topography (as measured by magnification factor) was indistinguishable between trained and untrained animals. On the other hand, the influence of contextual stimuli placed outside the receptive field showed a change consistent with the trained discrimination. Furthermore, this property showed task dependence, only being manifest when the animal was performing the trained discrimination.

Animals↗

Fast cerebral functional signal in the 100-ms range detected in the visual cortex by frequency-domain near-infrared spectrophotometry.

Brain activity is associated with physiological changes, which alter the optical properties of the tissue in the near-infrared part of the spectrum. Two major types of optical signals following functional brain activation can be distinguished: a slow signal due to hemodynamic changes and a fast signal, which is directly related to neuronal activity. The fast signal is small and therefore difficult to detect. We used a specially noise-optimized frequency-domain near-infrared spectrometer with a pi-sensor, which was expected to be particularly sensitive to deeper tissue layers, to investigate the human visual cortex during visual stimulation generated by a checkerboard. We were able to detect significant fast signals in single light bundles, but not in pi-signals. The fast signals were mostly collocated with strong slow hemodynamic signals, but showed a higher degree of localization than the latter. The latencies of 40 +/- 16 ms of the fast signals were similar between locations. Our results also indicate that the brain responds differently to a single and double (forth and back) reversal of the checkerboard, with a stronger reaction upon the double reversal.

Adult↗

Corticothalamic projections from the primary visual cortex in rats: a single fiber study using biocytin as an anterograde tracer.

This study investigates the pattern of axonal projections of single corticothalamic neurons from the rat primary visual cortex. Microiontophoretic injections of biocytin were made in cortical laminae V and VI to label small pools of corticothalamic cells and their intrathalamic axonal projections. After a survival period of 48 h, the animals were perfused and the tissue was processed for biocytin histochemistry. On the basis of the intrathalamic distribution of axonal fields and the types of terminations found in the thalamus, three types of corticothalamic projections were identified. (1) Cells of the upper part of lamina VI projected to the dorsal lateral geniculate nucleus where they arborized in rostrocaudally oriented bands or "rods" parallel to the lines of projection of retinal afferents. (2) Cells of the lower part of lamina VI projected to the lateral part of the lateral posterior nucleus and they also sent collaterals to the dorsal lateral geniculate nucleus where they participated in the formation of rods. (3) The corticothalamic projection of lamina V cells originated from collaterals of corticofugal cells whose main axons reached the tectum and/or the pontine nuclei. These collaterals never terminated within the dorsal lateral geniculate nucleus; they arborized in the lateral posterior, lateral dorsal and ventral lateral geniculate nuclei. All corticothalamic cells from lamina VI displayed the same type of axonal network made of long branches decorated by terminal boutons emitted "en passant" at the tip of fine stalks. Corticothalamic fibers arising from lamina V, however, generated varicose endings in restricted regions of their target nuclei. All corticothalamic axons derived from lamina VI cells, but not those derived from lamina V cells, gave off collaterals as they traversed the thalamic reticular complex. These results demonstrate that corticothalamic fibers arising from the rat primary visual cortex display a lamina-dependent projection pattern. In the light of previous studies on the topographical organization of corticothalamic projections, it is proposed that a similar organizational plan characterizes corticothalamic relationships in other sensory systems in the rat and in other species.

Animals↗

The effect of visual cortex lesions on vertical optokinetic nystagmus in the cat.

Vertical optokinetic nystagmus (VOKN) was measured before and after visual cortex lesions using the magnetic search coil technique. In normal cats, upward motion elicits higher slow phase gain than downward motion, especially at high stimulus velocities. Following decortication, the gain of upward VOKN may be attenuated by as much as 35% at stimulus velocities of 20% or more. This high velocity deficit in upward VOKN is consistent with the results of single unit studies of the lateral terminal nucleus (LTN) of the accessory optic system which suggest that visual cortical input (via the LTN) makes a direction specific contribution to the motion sensitivity of VOKN.

Animals↗

Experience-dependent regulation of the zincergic innervation of visual cortex in adult monkeys.

Zinc is packaged in, and released from, a subset of glutamatergic synapses in the mammalian telencephalon where it has been shown to act as a potent neuromodulator. In order to establish the functional role for zincergic neurons in visual cortical function and plasticity we have compared the topographic distribution of zincergic terminals in the primary visual cortex (V1) of normal adult vervet monkeys (Cercopithicus aethiops) to that in monkeys monocularly deprived of visual input for short (24 h) or long (3 months) survival times. In normal animals, staining levels for zinc were highest in layers 1-3, 4b, 5 and 6 and lowest in layers 4a and 4c. The laminar and tangential patterns of zinc staining were complementary to staining patterns demonstrated using cytochrome oxidase (CO) histochemistry. Following 3 months of monocular deprivation by enucleation, levels of zinc staining in layers 3, 4calpha and 6a were heterogeneously reduced, clearly revealing the ocular dominance pattern in V1. When compared with the pattern of CO staining, levels of both CO and zinc were reduced in cortical territory innervated by the enucleated eye. Zinc histochemistry also revealed the ocular dominance pattern after only 24 h of monocular impulse blockade induced by enucleation or intravitreal tetrodotoxin infusion. However, by either means of deprivation for 24 h, levels of zinc were increased in deprived-eye stripes relative to nondeprived-eye stripes. These results indicate that zincergic terminals demarcate distinct compartments in the primate visual cortex. Furthermore, levels of synaptic zinc are rapidly and dynamically regulated, suggesting that zinc and/or zincergic neurons participate in mediating activity-dependent changes in the organization of the adult neocortex.

Animals↗

Combined activation and deactivation of visual cortex during tactile sensory processing.

The involvement of occipital cortex in sensory processing is not restricted solely to the visual modality. Tactile processing has been shown to modulate higher-order visual and multisensory integration areas in sighted as well as visually deprived subjects; however, the extent of involvement of early visual cortical areas remains unclear. To investigate this issue, we employed functional magnetic resonance imaging in normally sighted, briefly blindfolded subjects with well-defined visuotopic borders as they tactually explored and rated raised-dot patterns. Tactile task performance resulted in significant activation in primary visual cortex (V1) and deactivation of extrastriate cortical regions V2, V3, V3A, and hV4 with greater deactivation in dorsal subregions and higher visual areas. These results suggest that tactile processing affects occipital cortex via two distinct pathways: a suppressive top-down pathway descending through the visual cortical hierarchy and an excitatory pathway arising from outside the visual cortical hierarchy that drives area V1 directly.

Adult↗

Nuclear respiratory factor-2 subunit protein: correlation with cytochrome oxydase and regulation by functional activity in the monkey primary visual cortex.

Previous studies have shown that a transcription factor of the Ets family, nuclear respiratory factor 2 (NRF-2), can activate in vitro the gene expression of cytochrome oxidase (CO), a mitochondrial enzyme of oxidative metabolism. The goals of our present study were to determine whether the distribution of NRF-2 alpha subunit proteins correlated with that of CO activity in the macaque monkey visual cortex and whether the level could be perturbed by visual deprivation. We generated polyclonal antibodies specifically against human NRF-2 alpha subunit. In normal monkeys, patterns of NRF-2 alpha distribution resembled closely that of CO activity: 1) NRF-2 alpha immunoreactivity was localized in both nuclei and cytoplasm of neurons, but the levels differed among various laminae; 2) layers IVA, IVC, and VI, which had high CO activity, were labeled more densely by NRF-2 alpha than layers I, IVB, and V, which contained lower levels of both NRF-2 alpha and CO activity; and 3) CO-rich puffs in layers II and III contained a higher level of NRF-2 alpha than CO-poor interpuffs. From 1 day to 7 days after monocular impulse blockade with tetrodotoxin, there was a progressive reduction of NRF-2 alpha in deprived ocular dominance columns, in parallel with decreases in CO activity. These results suggest that local levels of NRF-2 in the monkey visual cortex closely reflect neuronal physiological and metabolic levels revealed by CO activity and that the expression of NRF-2 alpha, like that of CO, is regulated tightly by neural functional activity.

Amino Acid Sequence↗

Anatomical evidence of subcortical contributions to the orientation selectivity and columns of the cat's primary visual cortex.

Physiological studies have demonstrated a subcortical origin for orientation selectivity and the orientation columns of the primary visual cortex. However, there are no anatomical data showing how subcortical cells contribute to this important property. Optical imaging, combined with 1,1'-dioctadecyl-3,3,3,3'-tetramethylin-docarbocyanine perchlolate (DiI) and biocytin retrograde tracing, reveals that relay cells projecting to a single orientation column representing the horizontal meridian were clustered within 300 microm in the dorsal lateral geniculate nucleus (LGN). Interestingly, some labeled cells were located on a line parallel to an iso-elevation line in the LGN. Thus, according to the quantitative projection of the visual field to the LGN (J. Comp. Neurol. 143 (1971) 101), their receptive fields must distribute horizontally in alignment in the visual field providing the first anatomical evidence for Hubel and Wiesel's model of simple cell receptive fields (J. Physiol. 160 (1962) 106).

Action Potentials↗

Developmental expression of intracellular targets of cGMP in rat visual cortex and alteration with dark rearing.

We describe the temporal pattern of mRNA expression of some of the molecular components of the NO/cGMP second messenger system in the developing rat visual cortex and the effect of dark rearing on their expression levels using semiquantitative RT-PCR. mRNA expression for these molecules was altered by dark rearing in one of three ways: (1) no change--rod, olfactory, and cone/testis CNG channels, nonselective cation channels gated by cyclic nucleotides and highly permeable to Ca2+; (2) decrease--cyclic nucleotide phosphodiesterases which regulate cyclic nucleotide levels, and soluble guanylyl cyclase, the key synthetic enzyme producing cGMP and potently activated by nitric oxide; and (3) increase--cGMP kinase 1, a key enzyme activated by cGMP to phosphorylate a variety of intracellular proteins including cytoskeletal elements. These data suggest important and distinct roles for the cGMP system in both early and late developmental events in the rat visual cortex.

3',5'-Cyclic-AMP Phosphodiesterases↗

Receptive field structure in the visual cortex: does selective stimulation induce plasticity?

Sensory areas of adult cerebral cortex can reorganize in response to long-term alterations in patterns of afferent signals. This long-term plasticity is thought to play a crucial role in recovery from injury and in some forms of learning. However, the degree to which sensory representations in primary cortical areas depend on short-term (i.e., minute to minute) stimulus variations remains unclear. A traditional view is that each neuron in the mature cortex has a fixed receptive field structure. An alternative view, with fundamentally different implications for understanding cortical function, is that each cell's receptive field is highly malleable, changing according to the recent history of the sensory environment. Consistent with the latter view, it has been reported that selective stimulation of regions surrounding the receptive field induces a dramatic short-term increase in receptive field size for neurons in the visual cortex [Pettet, M. W. & Gilbert, C. D. (1992) Proc. Natl. Acad. Sci. USA 89, 8366-8370]. In contrast, we report here that there is no change in either the size or the internal structure of the receptive field following several minutes of surround stimulation. However, for some cells, overall responsiveness increases. These results suggest that dynamic alterations of receptive field structure do not underlie short-term plasticity in the mature primary visual cortex. However, some degree of short-term adaptability could be mediated by changes in responsiveness.

Animals↗

Maternal exposure to polychlorinated biphenyls inhibits long-term potentiation in the visual cortex of adult rats.

Rats were exposed prenatally to the coplanar congener 3,3',4,4'-tetrachlorobiphenyl (TCB). The amount of long-term potentiation (LTP) was measured in slices from the visual cortex and hippocampus of the adult males as well as of controls. While in the cortical slices from the controls a stable LTP could be induced, LTP was inhibited in the TCB-exposed rats. In hippocampal slices, the amount of LTP was not significantly different between the two groups. Our results suggest that the visual cortex of adult animals is functionally altered by TCB if the exposure takes place during embryonic development.

Animals↗

The effect of age on binding of MK-801 in the cat visual cortex.

We have examined the effect of age on the binding of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine maleate (MK-801) in the cat visual cortex. We hypothesized that this binding might change with age because: (1) MK-801 binds to a site associated with the N-methyl-D-aspartate (NMDA) receptor; (2) the NMDA receptor complex has been implicated in neural plasticity; (3) plasticity in the cat visual cortex is age dependent. We used standard receptor binding techniques to measure MK-801 binding in membrane homogenates in cats aged 7 days (d), 21 d, 43 d, 83 d, 7-8 months (mo) and over 2 years. Glutamate (100 microM), glycine (30 microM) and spermidine (20 microM) were used to enhance binding. We found that MK-801 binding is maximal at about 6 weeks of age, decreases slightly by 83 days and then decreases more dramatically in adults. Saturation analysis showed that the of binding with age resulted from variation in number of binding sites and not from variation in affinity. The ability of Mg2+ to inhibit MK-801 binding did not change with age. Dark rearing did not alter the development of MK-801 binding sites.

Aging↗

A study of geniculate unit activity during cryogenic blockade of the primary visual cortex in the cat.

In cats under nembutal or chloralose anesthesia, unilateral temporary cryogenic blockades of the primary visual cortex were performed and their influence on unitary responses to restricted light spots was tested in the ipsilateral geniculate nucleus. No significant effect could thus be observed, at variance with previous positive results obtained by our group in structures like superior colliculus and pulvinar complex using the same experimental procedure.

Animals↗

Strength of figure-ground activity in monkey primary visual cortex predicts saccadic reaction time in a delayed detection task.

When and where are decisions made? In the visual system a saccade, which is a fast shift of gaze toward a target in the visual scene, is the behavioral outcome of a decision. Current neurophysiological data and reaction time models show that saccadic reaction times are determined by a build-up of activity in motor-related structures, such as the frontal eye fields. These structures depend on the sensory evidence of the stimulus. Here we use a delayed figure-ground detection task to show that late modulated activity in the visual cortex (V1) predicts saccadic reaction time. This predictive activity is part of the process of figure-ground segregation and is specific for the saccade target location. These observations indicate that sensory signals are directly involved in the decision of when and where to look.

Animals↗