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The role of functional MR imaging in patients with ischemia in the visual cortex.

BACKGROUND AND PURPOSE: Functional MR (fMR) imaging is based on changes in regional blood flow. The purpose of this study was to evaluate the role of fMR imaging for detection of a vascular compromised status in the occipital lobe in patients with ischemia in the visual cortex. METHODS: We performed fMR imaging in seven control subjects and seven patients with symptoms and signs of visual cortical transient ischemia and/or infarct. fMR imaging was performed using a gradient-echo sequence with the 2D fast low-angle shot technique. An axial slice including both visual cortices was selected, and stimulation of the visual cortex was performed using a red photostimulator. The number of activated pixels in each primary visual cortex area were counted and an asymmetry ratio [AR (%) = 100 x (R-L)/(R+L)/2] was calculated. Patients and control subjects underwent visual field examination, conventional MR imaging, and vascular imaging (MR angiography in all patients and control subjects, conventional catheter angiography in two patients). fMR imaging results were compared with the results of a visual field examination, conventional MR imaging, and vascular imaging. RESULTS: fMR imaging of the patients showed significant activation asymmetry (P <.05) compared with that of control subjects. Vascular abnormalities in the posterior circulation were found in all seven patients. By conventional MR imaging, five patients were found to have infarction in the occipital lobe and the remaining two patients showed no abnormality. In visual field examination, six of the seven patients showed homonymous hemi- or quadrantanopsia suggesting postchiasmic abnormalities, and the remaining patient had normal findings. fMR imaging showed decreased activity in the visual cortices corresponding to vascular abnormalities (seven of seven patients), permanent infarction (five of seven patients), or visual field defect (six of seven patients). Two patients with normal conventional MR imaging had vascular lesions in the posterior circulation, and fMR imaging showed decreased activity in the corresponding visual cortices. One patient with normal visual field examination had multifocal stenosis in the posterior cerebral artery without infarction, and fMR imaging showed decreased activity in the corresponding visual cortex. CONCLUSION: fMR imaging of the visual cortex may be a sensitive method for the detection of vascular-compromised status in the occipital lobe.

Adult↗

Origin of orientation tuning in the visual cortex.

The results of recent experiments have thrown new light on the neuronal connections underlying orientation-selective responses in the primary visual cortex of adult animals. The pattern of afferent input from the lateral geniculate nucleus to the cortex appears to be specific for orientation, while intracortical inhibitory connections appear to be non-specific in this respect. Experimental and theoretical studies have suggested that the development of cortical cell orientation tuning is an activity-dependent process.

Animals↗

The spatial extent over which neurons in macaque striate cortex pool visual signals.

We recorded activity of single units in macaque monkey primary visual cortex (V1) to define the retinotopic extent of the visual inputs that drive or modulate V1 neuron responses in parafoveal and peripheral (calcarine) cortex. We used high-contrast drifting grating stimuli to define the extent of the area over which responses summate and the extent of the receptive-field surround. We found responses of most V1 cells to summate over 1 deg, with a suppressive surround typically twice that in diameter, though for some cells (even in parafoveal V1) surrounds exceeded 13 deg in diameter. Surprisingly, we found no significant laminar differences in these dimensions or in the strength of surround suppression. We found that surround suppression in most cells arises from both the ends and sides of the receptive field. Our measures indicate that the strongest modulatory input arises from regions immediately adjacent to the excitatory summation area. These physiological measures suggest that the high-contrast summation field of V1 neurons can be accounted for by the sum of lateral geniculate nucleus (LGN) inputs offered to the local cortical column, with monosynaptic lateral connections within area V1 adding the larger dimensions of the low-contrast summation field and the near surround. Neither of these inputs suffice to explain the largest surrounds, which most likely derive from feedback from extrastriate visual areas.

Animals↗

Activity-dependent changes in GAD and preprotachykinin mRNAs in visual cortex of adult monkeys.

Tachykinin-immunoreactive neurons are a subgroup of the GABA neuronal population in layer IVC of monkey primary visual cortex. Following brief periods of monocular deprivation in adult monkeys, immunoreactivity for both GABA and tachykinins is dramatically reduced in layer IV cells that lie within the deprived ocular dominance columns of this cortical area. The present study shows that these activity-dependent changes are associated with changes in mRNA levels but over different time courses. Radioactive antisense riboprobes derived from monkey-specific cDNAs were used to localize glutamic acid decarboxylase (GAD) and beta-preprotachykinin (beta PPT) mRNAs by in situ hybridization histochemistry. GAD and beta PPT mRNAs decreased in deprived ocular dominance columns of adult monkeys when neural activity was abolished in one eye by intraocular injections of tetrodotoxin (TTX). beta PPT mRNA levels fell within 5 d of deprivation and thus appeared to parallel the fall in immunodetectable tachykinin levels. By contrast, reduced GAD mRNA levels were detectable only after 15 d of deprivation and long after the fall in immunoreactive GAD and GABA levels has maximized. These results suggest that tachykinin gene expression is regulated by transcriptional mechanisms as part of the first response to reduced neural activity whereas the initial downregulation of immunoreactive GAD and GABA depends on posttranscriptional mechanisms. Following a more prolonged period of deprivation, a secondary mechanism for GAD regulation appears to be engaged at the level of gene transcription or possibly by changes in mRNA stability.

Animals↗

Are visual cortex maps optimized for coverage?

The elegant regularity of maps of variables such as ocular dominance, orientation, and spatial frequency in primary visual cortex has prompted many people to suggest that their structure could be explained by an optimization principle. Up to now, the standard way to test this hypothesis has been to generate artificial maps by optimizing a hypothesized objective function and then to compare these artificial maps with real maps using a variety of quantitative criteria. If the artificial maps are similar to the real maps, this provides some evidence that the real cortex may be optimizing a similar function to the one hypothesized. Recently, a more direct method has been proposed for testing whether real maps represent local optima of an objective function (Swindale, Shoham, Grinvald, Bonhoeffer, & Hübener, 2000). In this approach, the value of the hypothesized function is calculated for a real map, and then the real map is perturbed in certain ways and the function recalculated. If each of these perturbations leads to a worsening of the function, it is tempting to conclude that the real map is quite likely to represent a local optimum of that function. In this article, we argue that such perturbation results provide only weak evidence in favor of the optimization hypothesis.

Animals↗

Abnormal thalamocortical pathfinding and terminal arbors lead to enlarged barrels in neonatal GAP-43 heterozygous mice.

GAP-43 has been implicated in axonal pathfinding and sprouting, synaptic plasticity, and neurotransmitter release. However, its effect on cortical development in vivo is poorly understood. We have previously shown that GAP-43 knockout (-/-) mice fail to develop whisker-related barrels or an ordered whisker map in the cortex. Here we used cytochrome oxidase (CO) histochemistry to demonstrate that GAP-43 heterozygous (+/-) mice develop larger than normal barrels at postnatal day 7 (P7), despite normal body and brain weight. Using serotonin transporter (5HT-T) histochemistry to label thalamocortical afferents (TCAs), we found no obvious abnormalities in other somatosensory areas or primary visual cortex of GAP-43 (+/-) mice. However, TCA projections to (+/-) primary auditory cortex were not as clearly defined. To clarify the mechanism underlying the large-barrel phenotype, we used lipophilic (DiI) axon labeling. We found evidence for multiple pathfinding abnormalities among GAP-43 (+/-) TCAs. These axons show increased fasciculation within the internal capsule, as well as abnormal turning and branching in the subcortical white matter. These pathfinding errors most likely reflect failures of signal recognition and/or transduction by ingrowing TCAs. In addition, many DiI-labeled (+/-) TCAs exhibit widespread, sparsely branched terminal arbors in layer IV, reflecting the large-barrel phenotype. They also resemble those found in rat barrel cortex deprived of whisker inputs from birth, suggesting a failure of activity-dependent synaptogenesis and/or synaptic stabilization in (+/-) cortex. Our findings suggest that reduced GAP-43 expression can alter the fine-tuning of a cortical map through a combination of pathfinding and synaptic plasticity mechanisms.

Animals↗

Evidence for a nicotinic component to the actions of acetylcholine in cat visual cortex.

Radioligand binding assays, receptor autoradiography and iontophoresis have been used to look for evidence of a nicotinic component to the actions of acetylcholine in cat visual cortex. [3H]Nicotine bound to a uniform population of high affinity binding sites in cat primary visual cortex. This binding was inhibited by nicotine agonists and antagonists but not muscarinic antagonists. The concentration of nicotinic binding sites was about 10% of that of muscarinic binding sites measured with [3H]N-methylscopolamine. The muscarinic sites were resolved into M1 and M2 subtypes. Quantitative receptor autoradiography showed that there were muscarinic sites in all layers, although they were least abundant in layer IV of area 17. In contrast, the nicotinic sites were most concentrated in layer IV in area 17. The concentration of this labelling was reduced at the 17/18 border and also at the 18/19 border. Layer I of the cingulate and suprasylvian gyri were also labelled. Electrolytic lesions of the lateral geniculate nucleus (LGN) led to a loss of nicotinic binding sites in layer IV of area 17, indicating that these sites are most likely located on the LGN terminals. Iontophoresis of mecamylamine, a nicotinic antagonist, decreased evoked responses in visual cortex, providing evidence that the [3H]nicotine binding sites are functional receptors and suggesting that the release of acetylcholine onto these receptors on the LGN terminals facilitates the input of visual information into visual cortex.

Animals↗

[Changes in the reactivity of visual cortex neurons after local photic stimulation of their receptive fields].

In experiments on unanesthetized relaxed cats the recovery cycles of neuron responses in the primary visual cortex were investigated by means of double local light stimulation of the receptive fields. In most cases the reactivity recovery was not monotonous. A more drastic recovery from depression produced by the first stimulus as well as a more complete primary restoration of activity were observed in neurons with central receptive fields than in those with peripheral receptive fields. Differences in synchronization of inhibitory and excitatory inputs to neurons responsible for central and peripheral vision are discussed.

Animals↗

Thalamic afferents to the visual cortex in congenitally anophthalmic mice.

Retrograde cell labelling with horseradish peroxidase (HRP) has been used to study the thalamic afferents to the primary visual cortex (area 17) in mutant H1-ZRDCT-An ('eyeless') mice, in which the eyes are missing throughout development. Injections of HRP that were localised to a subregion of area 17, resulted in the labelling of a group of neurons in the ipsilateral dorsal lateral geniculate nucleus, showing the existence of a point-to-point connectivity. Many labelled cells were also found in other posterior thalamic nuclei especially in the lateral posterior nucleus which in normal animals contain very few or no labelled cells.

Animals↗

Ultrastructure of synapses and golgi analysis of neurons in neocortex of the lateral gyrus (visual cortex) of the dolphin and pilot whale.

Qualitative and computerized quantitative analyses of ultrastructural features of synapses in different layers of the primary visual cortex in the dolphin (Stenella coeruleoalba) and the pilot whale (Globicephala melaena) were carried out. Also, Golgi and cytoarchitectonic analyses were performed in the same species of cetaceans and, additionally, in Tursiops truncatus and Phocaena phocaena. It was found that on a synaptic level, as well as in cytoarchitectonic and Golgi features, the neocortex of cetaceans combines evolutionary progressive features and conservative features with a marked prevalence of the latter. Thus, the total number of synapses in visual neocortex in cetaceans is closer to this value in higher Primates. On the other hand, the laminar density of synapses per mm3 is generally the same in all layers in cetacean visual cortex and numerically is close to values found in small lissencephalic brains. Also, the synapse/neuron ratio in the dolphin visual cortex is of the same order as in cortices of rodents and lagomorphs and much higher than in cortices of advanced terrestrial mammals. Layers I and II contain approximately 70% of the total synapses in the cortical slab through visual cortex. Layer I also contains the extraverted dendrites of neurons of layer II and thus these two layers resemble a paleoarchicortical type of organization superimposed on a more typical neocortical organization of the lower cortical layers. In this respect the convexity neocortex of cetaceans is generally similar to the neocortices of phylogenetically ancient extant mammals such as basal Insectivora and Chiroptera.

Animals↗

AMPA glutamate receptor subunit 2 in normal and visually deprived macaque visual cortex.

Glutamate and its various receptors are known to play an important role in excitatory synaptic transmission throughout the CNS, including the primary visual cortex. Among subunits of the AMPA receptors (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid), subunit 2 (GluR2) is of special significance because it controls their Ca2+ permeability. In the past, this subunit has been studied mostly in conjunction with other AMPA subunits. The present study sought to determine if GluR2 alone has a distinct laminar distribution in the normal macaque visual cortex, and if its pattern correlated with that of cytochrome oxidase (CO) under normal and monocularly deprived conditions. In the normal adult cortex, GluR2 immunoreactivity (ir) had a patchy distribution in layers II/III, in register with CO-rich puffs. GluR2-ir highlighted the upper border of layer II, the lower border of layer IV (previously termed IVC(beta dark)) and, most prominently, layer VI. Labeled neurons were primarily of the pyramidal type present in the upper border and lower half of layer VI, layers II/III, and scattered in layers V and upper IVB. Labeled nonpyramidal cells were large in layer IVB and small in IVC(beta dark). Notably, the bulk of CO-rich layers IVC and IVA had very low levels of GluR2-ir. At fetal day 13, however, GluR2 labeling showed a honeycomb-like pattern in layer IVA not found in the adult. A fragment of GluR2 cDNA was generated from a human cDNA library, and in situ hybridization revealed an expression pattern similar to that of GluR2 proteins. After 1-4 weeks of monocular impulse blockade with tetrodotoxin (TTX), alternating rows of strong and weak GluR2-ir in layers VI and II/III appeared in register with CO-labeled dark and light ocular dominance columns in layer IVC and puffs in II/III, respectively. Our results indicate that various cortical layers are differentially influenced by glutamate. The bulk of the major geniculate-recipient layers IVC and IVA have low levels of GluR2, presumably favoring synaptic transmission via Ca(2+)-permeable glutamate receptors. GluR2 plays a more important role in supragranular and infragranular layers, where the initial geniculate signals are further modified and are transmitted to other cortical and subcortical centers. The maintenance of GluR2 in these output layers is governed by visual input and neuronal activity, as monocular impulse blockade induced a down-regulation of this subunit in deprived ocular dominance columns.

Amino Acid Sequence↗

Heterosynaptic facilitation of in vivo thalamocortical long-term potentiation in the adult rat visual cortex by acetylcholine.

Acetylcholine (ACh) plays a permissive role in developmental plasticity of fibers from the lateral geniculate nucleus (LGN) to the primary visual cortex (V1). These fibers remain plastic and express long-term potentiation (LTP) in adult rodents, but it is not known if ACh modulates this form of plasticity in the mature V1. We show that, in anesthetized rats, theta burst stimulation (TBS) of the LGN using 5 or 40 theta cycles produced moderate (approximately 20%) and stronger (approximately 40%) potentiation, respectively, of field postsynaptic potentials recorded in the ipsilateral V1. Basal forebrain stimulation (100 Hz) 5 min after TBS enhanced LTP induced by both weak (5 theta cycles) and strong (40 theta cycles) induction protocols. Both effects were reduced by systemic administration of the muscarinic receptor antagonist scopolamine. Basal forebrain stimulation did not enhance LTP when applied 30 min after or 5 min prior to TBS, suggesting that ACh affects early LTP induction mechanisms. Application of the cholinergic agonist carbachol in V1 by means of reverse microdialysis mimicked the effect of basal forebrain stimulation. We conclude that heterosynaptic facilitation of V1 plasticity by ACh extends beyond early postnatal maturation periods and acts to convert weak potentiation into pronounced, long-lasting increases in synaptic strength.

Acetylcholine↗

Responses of single units in cat visual cortex to moving bars of light as a function of bar length.

1. The responses of single units in the cat's primary visual cortex to moving bars have been examined quantitatively as a function of bar length.2. For about half the cells studied, very long bars evoked weaker responses than short bars, implying that there were inhibitory regions flanking the receptive field centre. In another quarter of the cell sample, there was evidence of flanking regions which were facilitatory in effect.3. The strength of the flanking regions was found to vary from cell to cell and there was no sudden transition between cells which were ;hyper-complex' and those which were not.4. Within the central region of the receptive field, the responses of most (but not all) cells increased with bar length. About half the cells responded to very short bars or spots of light, but about one in six would not respond at all to short bars.5. Correlations were sought between the properties of cells as simple or complex, their responsiveness to moving spots of light, the size of their receptive field centre and the polarity, strength and size of their receptive field flanks. Simple and complex cells with small receptive fields were more likely to respond well to spots, and to have strong inhibitory flanks.6. Correlations were also sought between the above properties and several other parameters of cell behaviour. Cells with strong inhibitory flanks were found to be more broadly tuned for orientation. Individual cells were also more broadly tuned for the orientation of short bars than of long bars.7. Evidence was obtained that spatial summation can be linear or non-linear for different cells.

Action Potentials↗

Contrast gain control in the visual cortex: monocular versus binocular mechanisms.

In this study, we compare binocular and monocular mechanisms underlying contrast encoding by binocular simple cells in primary visual cortex. At mid to high levels of stimulus contrast, contrast gain of cortical neurons typically decreases as stimulus contrast is increased (). We have devised a technique by which it is possible to determine the relative contributions of monocular and binocular processes to such reductions in contrast gain. First, we model the simple cell as an adjustable linear mechanism with a static output nonlinearity. For binocular cells, the linear mechanism is sensitive to inputs from both eyes. To constrain the parameters of the model, we record from binocular simple cells in striate cortex. To activate each cell, drifting sinusoidal gratings are presented dichoptically at various relative interocular phases. Stimulus contrast for one eye is varied over a large range whereas that for the other eye is fixed. We then determine the best-fitting parameters of the model for each cell for all of the interocular contrast ratios. This allows us to determine the effect of contrast on the contrast gain of the system. Finally, we decompose the contrast gain into monocular and binocular components. Using the data to constrain the model for a fixed contrast in one eye and increased contrasts in the other eye, we find steep reductions in monocular gain, whereas binocular gain exhibits modest and variable changes. These findings demonstrate that contrast gain reductions occur primarily at a monocular site, before convergence of information from the two eyes.

Animals↗

Paths of information flow through visual cortex.

The main route of information flow in the cerebral cortex is from the middle layers of cortex to upper and lower layers. However, upper layers of the cat primary visual cortex can be directly driven by inputs from secondary visual cortex when activity in middle layers is disrupted. Upper-layer activity can be driven either by middle layers or by direct corticocortical inputs. One consequence of this result is that areas of cortex thought to be carrying out low-order analysis may be able to extract considerable information from higher order areas.

Animals↗

Organization of sensory cortex in the East African hedgehog (Atelerix albiventris).

We investigated the organization of neocortex in the East African hedgehog (Atelerix albiventris) with microelectrode recordings from sensory areas that were later correlated with cytochrome oxidase patterns in sections of flattened cortex. The location of corticospinal projecting neurons was also examined and related to sensory areas by making small injections of wheat germ agglutinin-horseradish peroxidase into the spinal cord. Our goals were to determine how hedgehog cortex is organized, how much sensory areas overlap, and to compare results with recent findings in other insectivores. Evidence was found for three separate topographically organized somatosensory areas, two visual areas, and a caudolateral auditory area. A medial somatosensory area corresponded to S1, the primary somatosensory area, whereas two lateral areas partially encircled auditory cortex and corresponded to the parietal ventral area (PV) and the secondary somatosensory area (S2). Primary visual cortex (V1) was delineated by a caudomedial cytochrome oxidase dark oval, and a more lateral visual area between V1 and somatosensory cortex corresponded to V2, or area 18. Two patches of corticospinal projecting cells were found primarily overlapping S1 and S2. Some bimodal auditory and somatosensory responses were found in parts of PV and S2, but for the most part, areas had relatively sharp histochemically apparent and physiologically defined borders. The present results indicate that the caudal neocortex of hedgehogs has only a few sensory areas, corresponding to those commonly found in several other small-brained mammals. Hedgehog cortical organization differs significantly in somatotopy, number, and position of fields from that of closely related shrews and moles. Thus, clear specializations occur, even within the order Insectivora.

Animals↗

Cocaine administration decreases functional connectivity in human primary visual and motor cortex as detected by functional MRI.

Functional magnetic resonance imaging (fMRI) was conducted to observe the effects of cocaine administration on the physiological fluctuations of fMRI signal in two brain regions. Seven long-term cocaine users with an average age of 32 years and 8 years of cocaine use history were recruited for the study. A T2*-weighted fast echo-planar imaging (EPI) pulse sequence was employed at 1.5 T to acquire three sets of brain images for each subject under three conditions (at rest, after saline injection, and after cocaine injection [0.57 mg/kg]). Cross-correlation maps were constructed using the synchronous, low frequency signal from voxel time courses after filtering respiratory, cardiac, and other physiological noise. A quantitative evaluation of the changes in functional connectivity was made using spatial correlation coefficient (SCC) analysis. A marked 50% reduction in SCC values in the region of primary visual cortex and 43% reduction in SCC values in the region of primary motor cortex were observed after cocaine administration. This significant reduction in SCC values in these cortical regions is a reflection of changes in neuronal activity. It is suggested that the observed changes in low frequency components after acute cocaine administration during a resting, no-task situation may be used as a baseline reference source when assessing the effects of cocaine on task-driven activation or on mesolimbic dopamine pathways.

Adolescent↗

Regional distribution of binding sites for neuropeptide Y in cat and monkey visual cortex determined by in vitro receptor autoradiography.

The goal of this study was to elucidate the precise regional and laminar distribution of neuropeptide Y (NPY) binding sites in feline and primate visual cortex. By means of in vitro receptor autoradiography, NPY binding sites in primate and feline visual cortex were specifically labeled with 3H-NPY. In cat area 17, the highest density of NPY-binding sites was present in lamina I and the upper half of lamina II. The density then gradually decreased towards lamina VI. Areas 18 and 19 exhibited a similar binding site-density profile. The decrease in density from superficial to deep layers was more gradual in area 18 than in areas 17 and 19. In monkey primary visual cortex (V1), layer IVc presented a high concentration of NPY binding sites, in addition to a dense zone of binding sites in layer I. Monkey secondary visual cortex (V2) displays a similar dense zone in layer I, but lacks such high density of NPY binding sites in layer IV. Therefore, the border between primary and secondary visual cortex coincides with the abrupt disappearance of this latter high density in layer IV. In cat as well as in monkey visual cortex, no significant differences were found between regions representing central vision and those representing the peripheral parts of the visual field. Comparison of our results for NPY binding sites with the distribution of alpha 1-adrenergic receptors, as recently described by Rakic et al. (J. Neurosci. 8(10):3670-3690, 1988) for primate and Parkinson et al. (Brain Res. 457:70-78, 1988) for feline visual cortex, revealed that those two patterns are very similar.

Animals↗