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Consistent and precise localization of brain activity in human primary visual cortex by MEG and fMRI.

The tomographic localization of activity within human primary visual cortex (striate cortex or V1) was examined using whole-head magnetoencephalography (MEG) and 4-T functional magnetic resonance imaging (fMRI) in four subjects. Circular checkerboard pattern stimuli with radii from 1.8 to 5.2 degrees were presented at eccentricity of 8 degrees and angular position of 45 degrees in the lower quadrant of the visual field to excite the dorsal part of V1 which is distant from the V1/V2 border and from the fundus of the calcarine sulcus. Both fMRI and MEG identified spatially well-overlapped activity within the targeted area in each subject. For MEG, in three subjects a very precise activation in V1 was identified at 42 ms for at least one of the two larger stimulus sizes (radii 4.5 and 5.2 degrees ). When this V1 activity was present, it marked the beginning of a weak wave of excitations in striate and extrastriate areas which ended at 50 ms (M50). The beginning of the next wave of activations (M70) was also marked by a brief V1 activation, mainly between 50 and 60 ms. The mean separation between V1 activation centers identified by fMRI and the earliest MEG activation was 3-5 mm.

Adult↗

Concentration-dependent suppression by beta-adrenergic antagonists of the shift in ocular dominance following monocular deprivation in kitten visual cortex.

We showed that beta-adrenergic receptor antagonists blocked the shift in ocular dominance following brief monocular deprivation in young kittens. Localized microperfusion of propranolol into the kitten visual cortex reduced the expected shift in the ocular dominance approximately 2 mm away from the center of perfusion. The blocking effect, however, did not reach an area approximately 5 mm from the perfusion center, suggesting that beta blockers work in a concentration-dependent fashion in the present paradigm. We further studied the concentration-effect relationship by widely changing the concentration of beta blockers (propranolol and sotalol) stored in an osmotic minipump. The proportion of binocular cells increased from 0.13 to 0.67 when the concentration of propranolol was increased from 10(-6)M to 10(-2)M, giving the half-maximum effect (binocularity, 0.40) at about 10(-4)M propranolol. However, the maximum binocularity obtained with the sotalol perfusion under the comparable condition was apparently much lower (0.45) than that with propranolol. Accordingly, the half-maximum binocularity (0.30) was obtained at about 10(-5)M sotalol. We also noted the presence of a linear, inverse relation between the logarithmic concentration of the beta blockers and the extent of the shift in ocular dominance as measured by the proportion of monocular cells which responded exclusively to stimulation of the nondeprived eye. The latter decreased from 0.75 to 0.25, when the former was increased from 10(-6)M to 10(-2)M (in an osmotic minipump). The two beta blockers behaved similarly in this correlation. The intracortical spread of locally perfused [3H]propranolol was studied at the end of the cortical perfusion which lasted for a week. The radioactivity was highest at the perfusion center and rapidly declined with increasing distance, leveling off approximately 3 mm from the perfusion center. The average "dilution factor" of locally perfused [3H]propranolol was calculated as about 1/170 of the original solution in an area of physiological recordings (approximately 2 mm from the perfusion center). Applying the "dilution factor" of 1/170, we estimated the approximate concentration of beta blockers needed at the recording sites to obtain the half-maximum effect; it was about 5.8 X 10(-8)M for sotalol. Taken together, the present results were interpreted as suggesting that there is a positive correlation between the number of activated beta-adrenergic receptors within the visual cortex and the extent of changes in ocular dominance following monocular deprivation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Sensing the invisible: differential sensitivity of visual cortex and amygdala to traumatic context.

To what extent does emotional traumatic context affect sensory processing in the brain? A striking example of emotional impact on sensation is manifested in posttraumatic stress disorder (PTSD), in which a severe emotional trauma produces recurrent and vivid unpleasant sensory recollections. Here we report on an fMRI study exploring the sensory processing of trauma-related pictures in the visual cortex and amygdala in respect to PTSD. The impact of traumatic experience on brain responses was tested in relation to stimuli content and its level of recognition in a parametric factorial design. Twenty combat veterans, 10 with and 10 without PTSD, viewed backward-masked images of combat and noncombat content, presented at below, near, and above recognition thresholds. The response to combat content evoked more activation in the visual cortex in PTSD subjects than in non-PTSD subjects, only when images were presented at below recognition threshold. By contrast, the amygdala demonstrated increased activation in PTSD subjects irrespective of content and recognition threshold of the images. These intriguing findings are compatible with the notion that in PTSD, emotional traumatic experience could modify visual processing already at the preattentive level. On the other hand, lack of content specificity in the amygdala point to a possible predisposed mechanism for pathological processing of traumatic experience. The differential sensitivity of the amygdala and visual cortex to traumatic context implies distinct roles of limbic and sensory regions in the registration and recollection of emotional experience in the brain.

Adult↗

Pontine projection from striate and prestriate visual cortex in the macaque monkey: an anterograde study.

The projection from striate and prestriate visual cortex to the pontine nuclei has been studied in the macaque monkey by means of anterograde tracer techniques in order to assess the contribution of anatomically and functionally distinct visual cortical areas to the cortico-ponto-cerebellar loop. No projection to the pons was found from central or paracentral visual-field representations of V1 (striate cortex) or prestriate visual areas V2, and V4. Small patches of terminal labeling occurred after injections of tracer into more peripheral parts of V1, V2 and V3, and into V3A. The terminal fields were located most dorsolaterally in the anterior to middle third of the pons and were quite restricted in their rostro-caudal extent. Injections of V5, however, yielded substantial terminal labeling, stretching longitudinally throughout almost the entire pons. This projection could be demonstrated to arise from parts of V5 receiving input from central visual-field representations of striate cortex, whereas parts of V4 receiving similarly central visual-field input had no detectable projection to the pons. Its distribution may overlap to a large extent with the termination of tecto-pontine fibers and with the termination of fibers from visual areas in the medial bank (area V6 or PO) and lateral bank (area LIP) of the intraparietal sulcus, as well as from frontal eye fields (FEF). It appears that the main information relayed to the cerebellum by the visual corticopontine projection is related to movement in the field of view.

Animals↗

Post-critical period plasticity of callosal transfer to visual cortex cells of cats following early conditioning of monocular deprivation and late optic chiasm transection.

We studied whether plasticity-induced callosal transfer exists after the critical period for sensitivity of visual cortex cells in kittens postnatally monocularly deprived and in which interocular competition was cancelled by chiasm transection during adulthood. Callosal transfer was studied acutely (n = 3 cats) and chronically (n = 7) following the chiasm transection (OCAMD). For comparison, adult cats in which chiasm transection only was performed (OCA) were also studied acutely (n = 3) and chronically (n = 9). The results were also compared to cats in which monocular deprivation and chiasm transection were simultaneously performed (OCKMD) during development (n = 6) and to normal control cats (n = 18). Unit recording was extracellularly carried out in visual cortex areas 17 and 18 and their boundary region, where the corpus callosum is represented. When no interocular competition was allowed between the non-deprived and the deprived eye via the thalamocortical direct visual pathways on cortical cells, such as in the OCKMD cats, the absolute majority of the cells were ipsilaterally driven, regardless of which hemisphere was studied. Only a minor proportion (4.1%) of the cells had some contralateral input from the non-deprived eye in the hemisphere ipsilateral to the deprived eye, indicating almost no interhemispheric callosal transfer. A slight increase in the proportion of cells callosally driven from the non-deprived eye (9.8%), was found in this hemisphere in cats in which interocular competition was allowed via the direct visual pathways prior to its cancellation by chiasm transection (OCAMD), if studied acutely after the chiasm transection. A remarkable increase in callosal transfer was found in this hemisphere under chronic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Residual vision in a subject with damaged visual cortex.

It is well known that a lesion in the optic radiation or striate cortex leads to blind visual regions in the retinotopically corresponding portion of the visual field. However, various studies show that some subjects still perceive certain stimuli even when presented in the "blind" visual field. Such subjects either perceive stimuli abnormally or only certain aspects of them (residual vision) or, in some cases, deny perception altogether even though visual performance can be shown to be above chance (blindsight). Research on monkeys has suggested a variety of parallel extrastriate visual pathways that could bypass the striate cortex and mediate residual vision or blindsight. In the present study, we investigated a subject with perimetrically blind visual areas caused by bilateral brain damage. Black and white stimuli were presented at many locations in the intact and affected areas of the visual field. The subject's task was to state, using confidence levels, whether the target stimulus was black or white. The results revealed an area in the "blind" visual field in which the subject perceived a light flash when the experimental black stimulus was presented. We hypothesize that a spared region in the visual cortex most likely accounts for these findings.

Aged↗

Stereoselective effects of the novel anticonvulsant lacosamide against 4-AP induced epileptiform activity in rat visual cortex in vitro.

We examined effects of the novel anticonvulsant lacosamide and its inactive isomer (SPM 6953) in an in vitro model of epileptiform activity. Focal field potential recordings (34+/-0.2 degrees C) were obtained from 17 to 22 day old rat brain slices. Physiological synaptic transmission (fEPSP amplitude and duration) in CA1 of rat hippocampus was not significantly altered (P > 0.05, n = 4) by lacosamide (1 microM-1 mM). Recording from visual cortex during application of 4-aminopyridine (4-AP; 100 microM) revealed both spontaneous and evoked 'ictal like' discharges. Spontaneous ictal like discharges in the visual cortex were blocked by 100 microM carbamazepine (CBZ), 100 microM pentobarbital and 200 microM phenobarbital (PHB) but were insensitive to the anti-absence drug ethosuximide (750 microM; n = 4, P > 0.05). Lacosamide reduced tonic duration and maximal firing frequency with EC(50)s of 41 and 71 microM, respectively. In contrast, the S stereoisomer (100-320 microM) produced no significant effect on spontaneous ictal activity (n = 3-4, P > 0.05). Seizures induced by high frequency (100 Hz, 1s) stimulation were selectively reduced in amplitude by PHB (200 microM) and frequency by CBZ (100 microM; n = 6) and lacosamide (100 microM; n = 4). GABAergic negative going potentials were attenuated by CBZ (irreversible with washing) and lacosamide (reversible) but not by PHB. We conclude that lacosamide blocks 4-AP induced epileptiform activity in the visual cortex. This novel anticonvulsant drug appears to inhibit epileptogenesis (seizure spread) by interacting with a stereoselective, but as yet unidentified, target site in rodent neocortex in the mid-micromolar range.

2-Amino-5-phosphonovalerate↗

[Changes in the reactivity of the visual cortex neurons as affected by the posterolateral hypothalamus and the raphe nuclei of the midbrain].

Different types of the visual cortex neuronal responses to the 15-30 min rhythmic photostimulation under the effect of electrical stimulation of "positive" emotional hypothalamic area and that of midbrain raphe nuclei were revealed in rabbits: the synergic character of the effect of "positive" hypothalamic emotional area, midbrain raphe nuclei to reactive properties of the visual cortex neurons. The same regularity was observed in interrelation analysis of the cortical neurons recorded in the same cortex microvolume as revealed by cross-interval histogram technique. The data obtained suggest a dual role of serotoninergic mechanisms (mediator and modulator) in actualization of hypothalamic effect on the cortex processes.

Action Potentials↗

Visual cortex excitability in migraine evaluated by single and paired magnetic stimuli.

OBJECTIVE: To determine the excitability of the visual cortex by phosphene thresholds (PT) in patients with migraine using transcranial magnetic stimulation (TMS) with single- and paired-pulses. METHODS: Nineteen patients with migraine with aura (MWA), 19 patients with migraine without aura (MWoA), and 22 control subjects were included. Patients were free from preventive anti-migraine treatment and were investigated within 3 days before or after an acute migraine attack. In each subject, PT were assessed by single-pulse and paired-pulse TMS with an interstimulus interval of 50 ms. RESULTS: The main effect of diagnosis indicated that mean PT were significantly lower in migraine patients than in control subjects (P = .001). Using single-pulse TMS, mean PT tended to be lower in MWoA-patients (57.7 +/- 11.8%) compared with control subjects (64.4 +/- 10.5%) (P = .064). In MWA-patients, mean PT (53.1 +/- 5.7%) were significantly lower compared with controls (P < .001). Using TMS with paired pulses, mean PT were significantly reduced in MWoA-patients (40.3 +/- 4.9%, P = .017) as well as in MWA-patients (39.6 +/- 4.2%, P = .005) compared with controls (44.6 +/- 6.0%). The main effect of stimulation type indicated that mean PT were lower determined with paired-pulse stimulation than with single pulses (P < .001). CONCLUSIONS: PT are reduced in patients with migraine in the interictal state suggesting an increased excitability of visual cortical areas. Compared with single-pulse TMS, paired-pulse magnetic stimulation is more efficient to elicit phosphenes. This technique provides the opportunity to evaluate visual cortex excitability with lower stimulus intensities and less discomfort.

Adolescent↗

The combined effects of unilateral enucleation and rearing in a 'dim' red light on synapse-to-neuron ratios in the rat visual cortex.

One day old rats had their right eyes removed and together with non-enucleated controls were raised in either 'light' or 'dark' (red light) conditions from birth until 39 days of age. This resulted in four groups of animals: light-reared enucleated, light-reared non-enucleated, dark-reared enucleated and dark-reared non-enucleated. All animals were killed by intracardiac perfusion with 2.5% sodium cacodylate-buffered glutaraldehyde at 39 days of age. Pieces of visual cortex (Area 17) from both right and left cerebral hemispheres of each animal were dissected out and processed for electron microscopy. Stereological procedures were used to estimate the synapse-to-neuron ratios in Layers II-III of these cortices. Light-reared non-enucleated rats had about 16,000 synapses per neuron in both right and left visual cortices. Rearing non-enucleated rats in the dark reduced this value to about 11,500. The synapse-to-neuron ratio of unilaterally enucleated rats raised in the light was not significantly different from that observed in light-reared non-enucleated rats. Combined dark-rearing and unilateral enucleation did reduce the synapse-to-neuron ratio but not to any greater extent than did dark-rearing alone. However, there was a suggestion of a differential effect between the right and left cortices in these enucleated, dark-reared animals. These results demonstrate the importance of light stimulation for the normal development of interneuronal connectivity of the visual cortex. They also show that the effects of unilateral enucleation for the visual cortex are not as great as those previously observed for the superior colliculi in the same animals, at least as far as synapse-to-neuron ratios are concerned.

Animals↗

A comparison of the organization of the projections of the dorsal lateral geniculate nucleus, the inferior pulvinar and adjacent lateral pulvinar to primary visual cortex (area 17) in the macaque monkey.

Both anterograde and retrograde transport tracing methods were used to study the organization of the projections of the dorsal lateral geniculate (DLG), the inferior pulvinar and subdivisions of the lateral pulvinar to primary visual cortex (striate cortex or area 17). The DLG projects only to striate cortex. These projections are retinotopically organized, and do not extend to any cortical layers above layer IVA. In contrast the inferior pulvinar (PI) and the immediately adjacent portion of the lateral pulvinar (PL alpha 48) project to both striate and prestriate cortex. The projections from these two thalamic areas to the striate cortex are also retinotopically organized and exist in parallel with those from the DLG. In contrast to the DLG, the projections from PI and PL alpha terminate above layer IVA in striate cortex, i.e. layers I, II and III. In prestriate cortex the layers of termination include layers IV, III and I. The pulvinar terminations in layers II and III of area 17 occur in segregated patches as do the geniculate terminations in layers IVC and IVA. On the other hand the pulvinar terminations in layer I which overlie those in layers II and III of area 17 appeared to be continuous. Control studies show that the remainder of the lateral pulvinar overlying PL alpha does not project to striate cortex. It is concluded that there are 3 visuotopically organized inputs from the lateral thalamus to primary visual cortex and that each of these inputs have different layers of termination. The inputs from PI and DLG can convey direct retinal inputs while those from PI and PL alpha can also be involved in intrinsic cortico-thalamocortical connection with prestriate cortex. It remains, then that it cannot be tacitly assumed that the ascending inputs which influence the response properties of the primary cortical neurons arise solely from the dorsal lateral geniculate nucleus. It is also argued that these inputs to the supragranular layers may be excitatory as those from the DLG to the IVth layer.

Animals↗

Rapid remodeling of axonal arbors in the visual cortex.

If vision in one eye is blurred or occluded during a critical period in postnatal development, neurons in the visual cortex lose their responses to stimulation through that eye within a few days. Anatomical changes in the nerve terminals that provide input to the visual cortex have previously been observed only after weeks of deprivation, suggesting that synapses become physiologically ineffective before the branches on which they sit are withdrawn. Reconstruction of single geniculocortical axonal arbors in the cat after either brief or prolonged monocular occlusion revealed striking axonal rearrangements in both instances. Rapid withdrawal of the branches of deprived-eye arbors suggests that axonal branches bearing synapses respond quickly to changing patterns of neuronal activity.

Animals↗

Different inhibitory synaptic input patterns in excitatory and inhibitory layer 4 neurons of ferret visual cortex.

The synaptic mechanisms underlying the generation of orientation and direction selectivity in layer 4 of the primary visual cortex are still largely unclear. Previous in vivo work has shown that intra-cortical inhibition plays a major role in generating the properties of orientation and direction selectivity. Excitatory and inhibitory cortical neurons differ in their receptive field properties: excitatory neurons tend to be orientation- and direction-selective, inhibitory neurons tend to be orientation-, but not direction-selective. Here we have compared the relationship between direction preference maps recorded in vivo and synaptic input maps recorded in vitro from excitatory and inhibitory stellate cells in layer 4 of ferret visual cortex. Our goal was to test whether the differences in direction tuning between these cell populations might result from different inhibitory connectivity patterns. We found that excitatory neurons, which are direction tuned in vivo, receive approximately 50% of their inhibitory inputs from cortical regions of opposite direction preference whereas inhibitory cells, which are not or poorly direction tuned, receive only very few inputs from regions of opposite direction preference. This confirms that inhibitory connections arising in cortical regions of opposite direction preference may be required to create or strengthen direction tuning in their target neurons. Thus, differences in intracortical inhibitory circuit patterns may underlie the differences in receptive field properties observed between excitatory and inhibitory neurons in vivo.

Animals↗

Comparison of the expression of two forms of glutamic acid decarboxylase (GAD67 and GAD65) in the visual cortex of normal and dark-reared cats.

In normal development, there are dramatic changes in both the level and the laminar pattern of expression of the two forms of glutamate decarboxylase (GAD67, GAD65), the synthetic enzyme for gamma-aminobutyric acid (GABA). We have used antibodies to determine whether these normal postnatal changes in the expression of the two GADs depend on visual input by comparing normal and dark-reared cat visual cortex. Western blot analysis showed no significant differences in the levels of expression of the two enzymes between rearing conditions at either 5 or 20 weeks. Immunohistochemistry was used to compare the laminar distribution of the GADs in the two rearing conditions. At 1 week of age, both GAD67 and GAD65 immunoreactivity is concentrated in deep layers of visual cortex. At 5 and 20 weeks in both rearing conditions, GAD67-stained cells bodies were distributed rather uniformly across all cortical layers. GAD65 primarily labeled puncta (synaptic terminals) and these were also distributed rather uniformly across all visual cortical layers in both rearing conditions. Counts of GAD67-positive cell bodies and GAD65-positive puncta also revealed no differences between the rearing conditions. Thus, both GAD67, which produces the basal pool of GABA, and GAD65, which is specialized to respond to short-term increases in demand in synaptic terminals, developed normal levels of expression and normal intracellular and laminar distributions in the absence of visual input. Physiological studies suggest immaturity in the GABA system of dark-reared visual cortex. The present results indicate that such abnormalities are not due to presynaptic alterations in GABA synthetic enzymes.

Animals↗

Analysis of the postnatal growth of visual cortex.

Development and growth of V1 begins during embryogenesis and continues postnatally. The growth of V1 has direct implications on the organization of features such as the retinotopic map and the pattern of visual cortical columns. We have examined the postnatal growth and two-dimensional shape of V1 in macaque monkeys, cats, and rats. The perimeter, area, and anterior-posterior length of V1 were measured from unfolded and flattened sections from neonatal and adult animals from each of these species. Although there were substantial differences in the overall amount of postnatal growth, from 18% in macaque monkeys to more than 100% in cats, in all three species the shape of V1 did not change during development. Thus, growth of the mammalian visual cortex is well described as an isotropic expansion, so the layout of the global features, such as the arrangement of ocular dominance columns and the retinotopic map, does not need to change during development. Furthermore, quantification of the shape confirms the observations that there is a similar, egg-like oval shape to the visual cortex of these mammalian species.

Animals↗

N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine reduces intracellular calcium response to noradrenaline in rat visual cortex.

Using the fluorescent indicator Fura-2, we investigated the effects of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenergic neurotoxin, on intracellular calcium responses to noradrenaline, N-methyl-D-aspartate, and carbamylcholine chloride in brain slices of the rat visual cortex. Noradrenergic depletion in the visual cortex of young rats was induced by DSP-4, and its selectivity was confirmed by two different methods, i.e., immunostaining with anti-dopamine-beta-hydroxylase antibody and biochemical analysis by high-performance liquid chromatography. The treatment with DSP-4 (25 mg/kg i.p., x2) caused disruption of noradrenergic fibers throughout all cortical layers, and reduced the content of noradrenaline to 6.4% of that in the normal control. In the normal cortex, bath-applied noradrenaline (100 microM) increased the intracellular calcium to 123% of the control in terms of the F(340)/F(380) ratio of Fura-2 fluorescence. Quantitative analysis of the F(340)/F(380) ratio was performed in layers II to IV, since the increase was mainly observed in these layers. The intracellular calcium response to noradrenaline was significantly (P<0.0001) reduced in the DSP-4-treated animals to 63.2% of that in the normal control. The response to N-methyl-D-aspartate (100 microM) was also reduced, whereas the response to carbamylcholine chloride, a muscarinic cholinergic agonist (100 microM), was not affected by the DSP-4 treatment. From these findings we suggest that noradrenergic denervation by DSP-4 reduces the intracellular calcium response to noradrenaline through changes in the intracellular signal transduction.

Adrenergic Agents↗

Neurochemical correlates of gamma-aminobutyrate (GABA) inhibition in cat visual cortex.

High affinity binding of [3H]gamma-aminobutyric acid (GABA) to neuronal membranes from different parts of cat visual cortex was tested for sensitivity to GABA(A) agonists isoguvacine and THIP, GABA(A) antagonist SR95531 and GABA(B) agonist baclofen. Some of the GABA(A)-binding sites were found to have a very low affinity for THIP, suggesting the presence and, possibly, uneven distribution of "non-synaptic" GABA(A) receptors in cat visual cortex. There were no differences in Km and Vmax values of high affinity uptake of GABA and in the potency of K(+)-stimulated release of GABA, between primary and association cortices. Consequently, the present results indicate that despite the anatomical and physiological differences between the primary and association feline visual cortices the neurochemical characteristics of GABAergic inhibition are very similar in the two regions.

Animals↗

The chandelier cell of the human visual cortex: a Golgi study.

The size, location, distribution, and spatial orientation of the chandelier cell of the human visual cortex are described for the first time. The rapid Golgi method has been utilized to study the structural features of these inhibitory interneurons. The human chandelier cell is a small stellate interneuron with prominent idiodendritic and idioaxonic arborizations. These arborizations are distributed within a narrow rectangular tissue slab that measures approximately 300 X 200 X 100 microns. This relatively small and narrow functional territory is oriented perpendicular to the pial surface and to the long axis of the gyrus. The territory of distribution of its axon is larger than and encloses that of its dendrites. The number of specific axonic terminals (candles) per chandelier cell is also relatively small, ranging from 60 to 80 units. These axonic terminals represent the functional units of the neuron and reflect the number of pyramidal cell axons contacted by it. The chandelier cell of the human visual cortex possibly represents the smallest neuron of this kind described to date. The size of its functional territory and the number of its specific axonic terminals are among the smallest of any neuron of this kind thus far described. It is postulated herein that in the course of mammalian phylogeny the chandelier cell shows a tendency toward a progressive reduction in the size of its functional territory and in the number of its functional units (candles), as well as a tendency toward a more "idio" pattern of distribution for its axonic and dendritic arborizations. Perhaps, these progressive evolutionary modifications could reflect a tendency of this type of interneuron toward an increasing specialization. The possible existence of a relationship between the progressive transformation of the chandelier cell and the increasing visual acuity, dexterity, and skillfulness in the course of mammalian phylogeny should be explored.

Female↗