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Cortical direction selectivity without directional experience.

How neurones in the visual cortex acquire their response properties during postnatal development is an important question with far-reaching implications. In the present study, we demonstrate the developmental specification of geniculo-cortical afferents using our previously proposed model for the activity-dependent self-organization of neural networks. Our results indicate, in contrast to common beliefs, that both orientation and direction selectivity can be achieved in the primary visual cortex even if the retinae were never exposed to oriented and/or moving objects during development.

Geniculate Bodies↗

Asymptomatic ischemic cerebrovascular disorders and neuroprotection with vinpocetine.

The asymptomatic ischemic cerebrovascular disorders (AICVD) is an early manifestation of cerebrovascular disease. It is also known as latent insufficiency of the cerebrovascular circulation or as asymptomatic cerebrovascular disorders. Recently, the term subclinical disease, detected noninvasively, has been introduced by American Heart Association. The diagnosis is based on the following criteria: evidence of vascular risk factors; episodic nonspecific complaints without any focal cerebral symptoms; mild cognitive deficit, detected by neuropsychological tests; carotid ultrasonography often shows intimal-medial thickening, atherosclerotic plaques and carotid stenosis; CT and MRI occasionally reveal silent cerebral infarctions, white matter hyperintensities or cerebral atrophy; regional hypoperfusion above the ischemic threshold is also seen by rCBF measurements. Treatment of the AICVD, modifying the vascular risk factors and using neuroprotective agents, should be the cornerstone of primary prevention of ischemic stroke and cognitive decline, caused by cerebrovascular disorders. Vinpocetine has been found to interfere with various stages of the ischemic cascade: ATP depletion, activation of voltage-sensitive Na(+)- and Ca(++)-channels, glutamate and free radicals release. The inhibition of the voltage-sensitive Na(+)-channels appears to be especially relevant to the neuroprotective effect of vinpocetine. Pronounced antioxidant activity of the drug could also contribute to the neuroprotection. PET studies in primates and man showed that 11C labelled vinpocetine passes the blood-brain barrier rapidly. Heterogeneous brain distribution of the compound was observed mainly in the thalamus, basal ganglia, occipital, parietal and temporal cortex, regions which are closely related to the cognitive functions. PET studies in chronic ischemic stroke patients revealed favourable effects of vinpocetine on rCBF and glucose metabolism in the thalamus, basal ganglia and primary visual cortex. It seems, vinpocetine, affecting the multiple mechanisms of the AICVD, could be of benefit for the treatment in this early stage of cerebrovascular disease. Vinpocetine may also become a new therapeutic approach to prophylactic neuroprotection in patients at high risk of ischemic stroke.

Brain Ischemia↗

Different mechanisms for loss and recovery of binocularity in the visual cortex.

Diverse molecular mechanisms have been discovered that mediate the loss of responses to the deprived eye during monocular deprivation. cAMP/Ca2+ response element-binding protein (CREB) function, in particular, is thought to be essential for ocular dominance plasticity during monocular deprivation. In contrast, we have very little information concerning the molecular mechanisms of recovery from the effects of monocular deprivation, even though this information is highly relevant for understanding cortical plasticity. To test the involvement of CREB activation in recovery of responses to the deprived eye, we used herpes simplex virus (HSV) to express in the primary visual cortex a dominant-negative form of CREB (HSV-mCREB) containing a single point mutation that prevents its activation. This mutant was used to suppress CREB function intracortically during the period when normal vision was restored in two protocols for recovery from monocular deprivation: reverse deprivation and binocular vision. In the reverse deprivation model, inhibition of CREB function prevented loss of responses to the newly deprived eye but did not prevent simultaneous recovery of responses to the previously deprived eye. Full recovery of cortical binocularity after restoration of binocular vision was similarly unaffected by HSV-mCREB treatment. The HSV-mCREB injections produced strong suppression of CREB function in the visual cortex, as ascertained by both DNA binding assays and immunoblot analysis showing a decrease in the expression of the transcription factor C/EBPbeta, which is regulated by CREB. These results show a mechanistic dichotomy between loss and recovery of neural function in visual cortex; CREB function is essential for loss but not for recovery of deprived eye responses.

Animals↗

Multiple equivalent current dipole source localization of visual event-related potentials during oddball paradigm with motor response.

Event-related potentials (ERPs) during a visual oddball paradigm with button-pressing responses were recorded in 12 right-handed subjects from 32 scalp electrodes. The single equivalent current dipole (ECD) of the target C1 (weak occipito-parietal negativity from 30-80 ms) was consistently located at the primary visual cortex. From the 4-ECD localization of the target P1/N1 (temporally coincident frontal positivity and occipito-temporal negativity), it was suggested that this complex reflected activities from distributed sources along both dorsal occipito-parietal and ventral occipito-temporal areas. The stable multiple ECD solutions for the target P3b were chosen as those including the left primary motor and/or sensorimotor dipole and satisfying goodness-of-fit (GOF) of more than 98% and confidence limit (CL) of less than 1 mm. The obtained frontal dipoles were discussed in terms of visual working memory and sustained attention in reference to the previous PET, fMRI and MEG studies. The distributed multiple ECDs may suggest that P3 should be interpreted as being the embodiment of the cortico-limbic-thalamic network which involves Halgren and Marinkovic's emotional and behavioral model and Mesulam's attentional circuit.

Adult↗

High-resolution echo-planar fMRI of human visual cortex at 3.0 tesla.

Known specialized properties of the human visual cortex have been used to investigate the role of spatial resolution on fMRI using blood oxygenation level dependent (BOLD) echo-planar MRI at 3.0 tesla. The magnitude of BOLD signal changes has been examined at low (3.1 x 3.1 x 3.0 mm3) and high (0.8 x 1.6 x 3.0 mm3) resolution using both gradient-echo and spin-echo EPI. Paradigms were designed to activate primary visual cortex (V1/V2) and more specialized areas associated with detection of color (V4) and motion (V5). Sensitivity of activation maps increased at higher resolution despite the decreased total signal intensity at the smaller voxel size, presumably from reduced partial volume averaging. The greater microvascular selectivity of high-resolution spin-echo imaging enabled distinct activation patterns sensitive to motion to be detected in V1/V2 that were not apparent with gradient-echo imaging. The spatial resolution at 3.0 tesla was constrained by the size of physiological head motion relative to the voxel dimensions rather than SNR or the hemodynamic response of BOLD contrast. The higher spatial resolution at 3.0 tesla with more selective spin-echo EPI can further refine functional mapping within the cerebral cortex.

Brain Mapping↗

Synaptic plasticity of feedback connections in rat visual cortex.

The issue we want to address in the present paper is to establish whether electrical stimulation of latero medial (LM) area, a secondary visual area in the rat, is able to induce Long Term Potentiation (LTP) and Long Term Depression (LTD) in primary visual cortex (V1). To this aim rat slices containing area V1 and LM were prepared at P23 and P40 and field potentials in layers 2/3 of area V1 were recorded stimulating LM. We showed that it was never possible to induce LTP in area V1, unless bicuculline, a gamma-aminobutyric acid (GABA) receptors blocker, was applied to the slice. In contrast, LTD was normally inducible. Thus, cortical gabaergic circuitry in area V1 controls LTP but not LTD elicited by stimulation of feedback connections from LM.

Aging↗

Neurotransmitter systems in the visual cortex of the cat: possible involvement in plastic phenomena.

The aim of this paper is to review some of the investigations on neurotransmitter systems suggesting their possible role in visual information processing and their putative involvement in the plastic phenomena observed in the primary visual cortex of the cat. The neurotransmitters discussed include excitatory amino acids, ?-amino-butyric acid, acetylcholine, noradrenaline and serotonin. The following problems are discussed: (i) the occurrence and localization of the various neurotransmitter system components, (ii) the developmental changes of the components of a given neurotransmitter system, particularly in the critical period, (iii) the effects of manipulating the visual input on neurotransmitter system markers. It seems that especially during the critical period there exists a peculiar pattern of interactions between numerous neurotransmitters and neuromodulators. This may create unique conditions, which enable the visual cortical neurons to change their properties as a results of alterations of the visual input.

Animals↗

Altered metabolic activity in the cerebral cortex of rats exposed to ketamine.

Uptake of the metabolic marker, [3H]2-deoxy-D-glucose (2DG) was compared in rats given subanesthetic (50--100 mg/kg, i.p.) or anesthetic (200 mg/kg, i.v.) doses of ketamine with that in normal, unanesthetized rats. All doses of ketamine caused a relative increase of 2DG labeling in limbic regions, including the hippocampus, dentate gyrus, and cingulate, piriform, and entorhinal cortices. Striking 2DG-dense zones were confined to the molecular layer in the hippocampus, dentate gyrus, and entorhinal cortex. Subanesthetic doses of ketamine produced a relative reduction of 2DG uptake in layers I--IV of granular somatosensory cortex while sparing uptake in layer Va; therefore, the peak of dense uptake shifted from layer IV to layer Va. In regions of the somatosensory cortex which display a dysgranular layer IV, vertical columns of relatively dense 2DG uptake extended through all cortical layers. Columns of 2DG label also occurred outside of S1, in visual and auditory areas. In the primary visual cortex, this dose of ketamine decreased 2DG uptake relative to secondary visual cortex. Alteration of 2DG uptake in various cortical regions might be the consequence of a ketamine-induced activation of specific neuronal pathways with special neurochemical features. During subanesthetic ketamine administration, peak 2DG uptake shifts from cortical layer IV, which receives specific thalamocortical input, to layer Va, which receives projections via intrinsic cortical circuits. The ketamine-induced shift in the laminar focus of sensory cortical metabolism may reflect a functional disconnection from peripheral sensory input and/or enhanced internal (corticocortical) processing.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Visual and mental exploration of visuo-spatial configurations: behavioral and neuroimaging approaches.

Do mental imagery and perception involve common processing mechanisms? Imagery researchers have devoted a great deal of effort to establishing the functional and structural similarities between images and perceptual events. Recent studies have focused on the comparison of images that are reconstructions of previous perceptual experience and images constructed from verbal descriptions. This article reports the findings of a research program based on the mental scanning paradigm; they reveal the similarities and differences between the two kinds of mental images. Neuroimaging studies have also provided evidence that the parieto-occipital cortex is involved in the processing of visual images, whether they are based on perceptual experience or constructed from linguistic inputs. However, the PET studies conducted by our research groups provide no evidence that the primary visual cortex is engaged in the generation of visual images. As there is contradictory evidence about this, further research is needed to clarify the role of the early visual areas in mental visual imagery.

Brain Mapping↗

Pattern separation and synchronization in spiking associative memories and visual areas.

Scene analysis in the mammalian visual system, conceived as a distributed and parallel process, faces the so-called binding problem. As a possible solution, the temporal correlation hypothesis has been suggested and implemented in phase-coding models. We propose an alternative model that reproduces experimental findings of synchronized and desynchronized fast oscillations more closely. This model is based on technical considerations concerning improved pattern separation in associative memories on the one hand, and on known properties of the visual cortex on the other. It consists of two reciprocally connected areas, one corresponding to a peripheral visual area (P), the other a central association area (C). P implements the orientation-selective subsystem of the primary visual cortex, while C was modeled as an associative memory with connections formed by Hebbian learning of all assemblies corresponding to stimulus objects. Spiking neurons including habituation and correlated noise were incorporated as well as realistic synaptic delays. Three learned stimuli were presented simultaneously and correlation analysis was performed on spike recordings. Generally, we found two states of activity: (i) relatively slow and unordered oscillations at about 20-25 Hz, synchronized only within small regions; and (ii) faster and more precise oscillations around 50-60 Hz, synchronized over the whole simulated area. The neuron groups representing one stimulus tended to be simultaneously in either the slow or the fast state. At each particular time, only one assembly was found to be in the fast state. Activation of the three assemblies switched on a time scale of 100 ms. This can be interpreted as self-generated attention switching. On the time scale corresponding to gamma oscillations, cross correlations between local neuron groups were either modulated or flat. Modulated correlograms resulted if the groups coded features corresponding to a common object. Otherwise, the correlograms remained flat. This behavior is in agreement with experimental results, while phase-code models would generally predict modulated correlations also in the case of different objects. Furthermore, we derive a technical version from our biological associative memory model that accomplishes fast pattern separation parallel in O(log2 n) steps for n neurons and sparse coding.

Action Potentials↗

Functional study of the rat cortical microcircuitry with voltage-sensitive dye imaging of neocortical slices.

The computations performed within cortex are likely to be determined by its internal dynamics in addition to its pattern of afferent input. As a step toward characterizing these dynamics, we have imaged electrical activity in slices from rat primary visual cortex stained with the voltage-sensitive dye di-4-ANEPPS. In response to electrical stimulation two fluorescence signals of similar maximum amplitude are elicited, (i) A fast signal that peaks in a few milliseconds, is dependent on membrane voltage, and has a significant presynaptic component. This signal can be used to image electrical activity ratiometrically. (ii) A slow signal that peaks a few seconds after stimulation, does not reflect voltage changes, and may originate from changes in scattering properties of the slice and from interactions of the dye with the cells. The spatial pattern of fast signals obtained in response to focal stimulation of coronal slices is consistent with known interlaminar projection patterns. In tangential slices, imaging of fast signals reveals clustered horizontal responses. Finally, imaging of fast signals during epileptiform activation of the disinhibited circuit reveals propagating responses, without evidence for modular activation.

Animals↗

Detecting the orientation of short lines in the periphery.

PURPOSE: Visual information processing in the human cortex is based on a highly ordered representation of the surrounding world. In addition to the retinotopic mapping of the visual field, systematic variations of the orientation tuning of neurons have been described in the primary visual cortex. As a step to understanding the relationship between position and orientation representation, we investigated psychophysically the minimum spatial requirements for the determination of orientation at various positions across the visual field. We know that the shortest line whose orientation can be resolved varies with eccentricity, such that its length corresponds to slightly less than 0.2 mm projected onto the cortical surface. Along the horizontal meridian horizontal lines are detected with higher precision than vertical or oblique lines. In the present experiments, we tested whether this is a preference for horizontal lines or for lines that are orientated radially away from the fovea. METHODS: Human observers were tested with lines positioned at one vertical, two horizontal and two oblique meridians at eccentricities between 5 and 25 degrees. RESULTS/CONCLUSION: Three of the four subjects were most sensitive for targets aligned with the meridian of presentation. This suggests that the visual system has the highest resolution in directions radiating from the fovea, which may be particularly useful for the analysis of flow fields resulting from forward translation.

Humans↗

Source analysis of event-related cortical activity during visuo-spatial attention.

Recordings of event-related potentials (ERPs) were combined with structural and functional magnetic resonance imaging (fMRI) to study the spatio-temporal patterns of cortical activity that underlie visual-spatial attention. Small checkerboard stimuli were flashed in random order to the four quadrants of the visual field at a rapid rate while subjects attended to stimuli in one quadrant at a time. Attended stimuli elicited enhanced ERP components in the latency range 80-200 ms that were co-localized with fMRI activations in multiple extrastriate cortical regions. The earliest ERP component (C1 at 50-90 ms) was unaffected by attention and was localized by dipole modeling to calcarine cortex. A longer latency deflection in the 150-225 ms range that was accounted for by this same calcarine source, however, did show consistent modulation with attention. This late attention effect, like the C1, inverted in polarity for upper versus lower field stimuli, consistent with a neural generator in primary visual cortex (area V1). These results provide support to current hypotheses that spatial attention in humans is associated with delayed feedback to area V1 from higher extrastriate areas that may have the function of improving the salience of stimuli at attended locations.

Adolescent↗

Postnatal development of thalamic recipient neurons in the monkey striate cortex: I. Comparison of spine acquisition and dendritic growth of layer 4C alpha and beta spiny stellate neurons.

A quantitative study has been made from Golgi impregnations of the maturation of dendrites and their spines on spiny stellate neurons in the macaque monkey primary visual cortex. The neurons studied lay within either the alpha or the beta division of lamina 4C; previous workers have shown the alpha division neurons to be contacted by thalamic axon terminals arising from the magnocellular division of the lateral geniculate nucleus (LGN) of the thalamus and the beta division neurons to be contacted by parvocellular LGN inputs. Most thalamic terminals and perhaps the majority of other type 1 (Colonnier, '81), presumed excitatory, inputs to these cells make synaptic contacts on the tips of their dendritic spines. Measurement was made of relative changes in the total number of spines on these alpha and beta spiny neurons over age by measuring both spine density along the dendrites and dendritic arbor size in single 90-microns sections from Golgi rapid preparations. Our previous work (Lund et al., '77; Boothe et al., '79) showed a marked proliferation and attrition of spines and dendritic branches to occur in the early postnatal weeks; Rakic et al. ('86) have since proposed that there is a cortexwide synchrony of synapse acquisition and loss during this same period. However, different visual capacities channelled via the magnocellular and parvicellular geniculate relays show different maturational rates (Harwerth et al., '86). This study indicates that the anatomical maturation of spines on the alpha and beta neurons is not temporally coincident from birth to 30 weeks. During this period, phases of spine acquisition and loss on alpha neurons precedes similar phases on beta neurons. The alpha neurons carry a peak spine population at 5-8 weeks postnatal, whereas the beta neurons carry their peak spine populations between 8 and 24 weeks postnatal. At all ages prior to 30 weeks, the two sets of neurons carry quite different total spine populations. Close to 30 weeks of age, the total spine coverage has fallen on both sets of neurons and becomes identical between the alpha and beta neurons. In animals aged 30 weeks to adult, spine coverage per neuron is maintained at a common figure for the alpha and beta neurons despite further growth and disparate dendritic arbor sizes and different local spine densities in the two groups; this suggests that some common sampling paradigm between pre- and postsynaptic elements is adopted by the alpha and beta neurons and also suggests the development of a close functional correlation between the two sets of neurons.

Aging↗

Response latencies of neurons in visual areas MT and MST of monkeys with striate cortex lesions.

Cortical area, MT (middle temporal area) is specialized for the visual analysis of stimulus motion in the brain. It has been suggested [Brain 118 (1995) 1375] that motion signals reach area MT via two dissociable routes, namely a 'direct' route which bypasses primary visual cortex (area, striate cortex (V1)) and is specialized for processing 'fast' motion (defined as faster than 6 degrees/s) with a relatively short latency, and an 'indirect' route via area V1 for processing 'slow' motion (slower than 6 degrees/s) with a relatively long latency. We tested this proposal by measuring the effects of unilateral V1 lesions on the magnitudes and latencies of responses to fast- and slow-motion (depicted by random dot kinematograms (RDK) ) of single neurons in areas MT and medial superior temporal area (MST) of anaesthetized macaque monkeys. In the unlesioned hemisphere contralateral to a V1 lesion, response magnitudes and latencies of MT neurons were similar to those previously reported from MT neurons in normal monkeys, and there was no significant association between slow movement and long response latency (>100 ms), or between fast movement and short latency (< or =100 ms). V1 lesions led to diminished response magnitudes and increased latencies in area MT of the lesioned hemisphere, but did not selectively abolish MT responses to slow moving stimuli, or abolish long-latency responses to either slow- or fast-moving stimuli. Response magnitudes and latencies in area MST, which receives visual inputs directly from area MT and is also specialized for visual analysis of motion, were unaffected by V1 lesions (though we have shown elsewhere that directionally-selective responses in both areas were impaired by V1 lesions). Overall, the results are incompatible with the hypothesis that there are dissociable routes to MT specialized for processing separately fast and slow motion.

Action Potentials↗

Volatile anesthetics enhance flash-induced gamma oscillations in rat visual cortex.

BACKGROUND: The authors sought to understand neural correlates of anesthetic-induced unconsciousness. Cortical gamma oscillations have been associated with neural processes supporting conscious perception, but the effect of general anesthesia on these oscillations is controversial. In this study, the authors examined three volatile anesthetics, halothane, isoflurane, and desflurane, and compared their effects on flash-induced gamma oscillations in terms of equivalent concentrations producing the loss of righting reflex (1 minimum alveolar concentration for the loss of righting [MAC(LR)]). METHODS: Light flashes were presented every 5 s for 5 min, and event-related potentials were recorded from primary visual cortex of 15 rats with a chronically implanted bipolar electrode at increasing anesthetic concentrations (0-2.4 MAC(LR)). Early cortical response was obtained by averaging poststimulus (0-100 ms) potentials filtered at 20-60 Hz across 60 trials. Late (100-1,000 ms) gamma power was calculated using multitaper power spectral technique. Wavelet decomposition was used to determine spectral and temporal distributions of gamma power. RESULTS: The authors found that (1) halothane, isoflurane, and desflurane enhanced the flash-evoked early cortical response in a concentration-dependent manner; (2) the effective concentration for this enhancement was the lowest for isoflurane, intermediate for halothane, and the highest for desflurane when compared at equal fractions of the concentration that led to a loss of righting; (3) the power of flash-induced late (> 100 ms) gamma oscillations was augmented at intermediate concentrations of all three anesthetic agents; and (4) flash-induced gamma power was not reduced below waking baseline even in deep anesthesia. CONCLUSIONS: These findings suggest that a reduction in flash-induced gamma oscillations in rat visual cortex is not a unitary correlate of anesthetic-induced unconsciousness.

Anesthetics, Inhalation↗

More workload on the central executive of working memory, less attention capture by novel visual distractors: evidence from an fMRI study.

The present study examined the interaction of the central executive in working memory with visual attention. Native Chinese participants were given two versions of a number subtraction task, one of low demand and one of high demand, and were asked to ignore a simultaneously presented peripheral distractor. The distractor could be Chinese or Korean characters, familiar or novel to participants, respectively. Compared with the low-demand subtraction task, brain regions commonly associated with central executive functions, including left middle prefrontal cortex, anterior cingulate cortex, and precentral gyrus/sulcus, were significantly activated in the high-demand task. Critically, there was a significant interaction between distractor type and task demand. Novel distractors captured attention and elicited automatic visual analysis, shown by primary visual cortex activation, only when the subtraction task was of low demand but not when it was of high demand. The results provide confirmatory evidence that the extent to which higher level cognitive resources, specifically, the central executive component of working memory, are absorbed by a cognitive task has an impact upon automatic processing that occurs in response to distracting items.

Adult↗

A direct brainstem-amygdala-cortical 'alarm' system for subliminal signals of fear.

We examined whether consciously undetected fear signals engage a collateral brainstem pathway to the amygdala and prefrontal cortex in the intact human brain, using functional neuroimaging. 'Blindsight' lesion patients can respond to visual fear signals independently from conscious experience, suggesting that these signals reach the amygdala via a direct pathway that bypasses the primary visual cortex. Electrophysiological evidence points to concomitant involvement of prefrontal regions in automatic orienting to subliminal signals of fear, which may reflect innervation arising from brainstem arousal systems. To approximate blindsight in 22 healthy subjects, facial signals of fear were presented briefly (16.7 ms) and masked such that conscious detection was prevented. Results revealed that subliminal fear signals elicited activity in the brainstem region encompassing the superior colliculus and locus coeruleus, pulvinar and amygdala, and in fronto-temporal regions associated with orienting. These findings suggest that crude sensory input from the superior colliculo-pulvinar visual pathway to the amygdala may allow for sufficient appraisal of fear signals to innervate the locus coeruleus. The engagement of the locus coeruleus could explain the observation of diffuse fronto-temporal cortical activity, given its role in evoking collateral ascending noradrenergic efferents to the subcortical amygdala and prefrontal cortex. This network may represent an evolutionary adaptive neural 'alarm' system for rapid alerting to sources of threat, without the need for conscious appraisal.

Adult↗