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Excitability changes induced in the human primary visual cortex by transcranial direct current stimulation: direct electrophysiological evidence.

PURPOSE: Transcranial direct current stimulation (tDCS) has been shown to modify the perception threshold of phosphenes elicited by transcranial magnetic stimulation (TMS). The current study was undertaken to examine whether tDCS, when applied over the occipital cortex, is also able to affect visual-evoked potentials (VEPs), which characterize occipital activation in response to visual stimulation, in a polarity-specific way. METHOD: For this purpose, VEPs evoked by sinusoidal luminance grating in an on/off mode were recorded before, immediately after, and 10, 20, and 30 minutes after the end of 5, 10, or 15 minutes of anodal or cathodal tDCS of the primary visual cortex. RESULTS: Significant effects were observed only when low-contrast visual stimuli were applied. Cathodal stimulation decreased, whereas anodal stimulation increased the amplitude of the N70 component. The effect of cathodal stimulation was significant immediately after and 10 minutes after the end of stimulation, if the stimulation duration was sufficiently long (i.e., 10-15 minutes). An increase of N70 amplitude by anodal stimulation was significant only 10 minutes after the end of the 15 minutes tDCS. Cathodal stimulation tended also to affect the amplitude of the P100 component; however, the effect of stimulation was inverse. The amplitude increased immediately after the end of cathodal stimulation. In contrast, anodal stimulation did not affect the P100. The latencies of the N70 and the P100 were not affected by tDCS. CONCLUSIONS: tDCS appears to be a suitable method of inducing reversible excitability changes in a polarity-specific way, not only in the motor but also in the primary visual cortex. The duration of the induced aftereffects depends not only on stimulation duration but also on stimulation polarity. Cathodal stimulation seems to be more effective, in line with previous reports on the motor cortex.

Adult↗

What geometric visual hallucinations tell us about the visual cortex.

Many observers see geometric visual hallucinations after taking hallucinogens such as LSD, cannabis, mescaline or psilocybin; on viewing bright flickering lights; on waking up or falling asleep; in "near-death" experiences; and in many other syndromes. Klüver organized the images into four groups called form constants: (I) tunnels and funnels, (II) spirals, (III) lattices, including honeycombs and triangles, and (IV) cobwebs. In most cases, the images are seen in both eyes and move with them. We interpret this to mean that they are generated in the brain. Here, we summarize a theory of their origin in visual cortex (area V1), based on the assumption that the form of the retino-cortical map and the architecture of V1 determine their geometry. (A much longer and more detailed mathematical version has been published in Philosophical Transactions of the Royal Society B, 356 [2001].) We model V1 as the continuum limit of a lattice of interconnected hypercolumns, each comprising a number of interconnected iso-orientation columns. Based on anatomical evidence, we assume that the lateral connectivity between hypercolumns exhibits symmetries, rendering it invariant under the action of the Euclidean group E(2), composed of reflections and translations in the plane, and a (novel) shift-twist action. Using this symmetry, we show that the various patterns of activity that spontaneously emerge when V1's spatially uniform resting state becomes unstable correspond to the form constants when transformed to the visual field using the retino-cortical map. The results are sensitive to the detailed specification of the lateral connectivity and suggest that the cortical mechanisms that generate geometric visual hallucinations are closely related to those used to process edges, contours, surfaces, and textures.

Hallucinations↗

Simple cells may lie at the basis of mach bands: evidence from physiological studies in the cat's visual cortex.

Mach bands are a visual illusion evoked by a luminance ramp dividing two luminance plateaux (blurred edges), but not by sharp edges. Recently, two physiology-based models have tried to cope with the psychophysical data concerning this phenomenon. The basic components of both models are neurons with even- or odd-symmetric receptive fields (RFs). Both models predict that odd-symmetric cells respond better to sharp edges, while even-symmetric cells respond better to blurred ones. We have measured the responses of 34 primary visual cortex simple cells of the cat to blurred edges of various degrees. Twenty-one cells had RFs of even symmetry, responding best to blurred edges than to sharp ones. The rest were odd-symmetric cells, of which 12 responded best to sharp edges, and only one exceptional cell responded best to a 0.85 degrees-wide edge. Thus, the different cell types responded as predicted by the two different Mach band models. Simple cells may thus serve as the physiological basis of the psychophysical phenomenon of Mach bands. Furthermore, our evidence suggests the existence of inhibition between odd- and even-symmetric cells, as predicted by one of the models.

Animals↗

Temporal summation of magnetic response to chromatic stimulus in the human visual cortex.

The temporal-summation characteristics of the human visual cortex were investigated by recording the magnetic responses to isoluminant red-green gratings. In one condition, exposure duration (ED) of a single-pulse stimulus was varied between 16.7 ms and 200 ms, and in the other, stimulus-onset-asynchrony (SOA) of a double-pulse (presented for 16.7 ms each) stimulus was varied between 16.7 ms and 200 ms. The magnetic responses showed an initial peak at a latency of around 100 ms, the origin of which was estimated to be in the vicinity of the striate cortex. The peak amplitude increased with increasing ED and decreased with increasing SOA, showing a clear sign of temporal summation. The critical ED and SOA estimated from the peak amplitude vs. ED/SOA functions were about 50 ms. These values indicate the upper limit of temporal summation for chromatic stimuli in the human early visual cortex.

Adult↗

A systematic map of direction preference in primary visual cortex.

Neurons in the primary visual cortex respond selectively to the orientation of edges and their direction of motion. Orientation preference is mapped in a systematic fashion across the cortical surface, such that neurons in adjacent columns have similar but slightly shifted preferred orientations. Microelectrode studies have suggested that direction preference is also arranged in a systematic fashion, but exactly how this response property is mapped remains unclear. Here we show by optical imaging of intrinsic signals in ferret cortical area 17 that there is a mosaic-like map of direction preference. This map consists of numerous regions within which direction preference changes in a slow, continuous fashion. These regions are separated by winding boundaries (fractures) across which direction preference shifts abruptly, often by 180 degrees. Comparison of direction and orientation preference maps shows that these fractures subdivide iso-orientation domains into regions selective for opposite directions of motion.

Animals↗

Lesion-induced changes in NMDA receptor subunit mRNA expression in rat visual cortex.

Focal lesions in the visual cortex are well known to induce pronounced perilesional reorganization of the neuronal circuitry. Since NMDA receptors crucially control synaptic plasticity and reorganization, we studied lesion-induced changes in their subunit expression and biophysical properties. Between 8 and 10 days after focal thermolesioning, pyramidal neurones in the near surround of the lesion were studied in acute brain slices. We found a significant decrease in the ratio of NR2A and NR2B subunit mRNA as compared to neurones from sham operated animals. Interestingly, no significant differences in the properties of NMDA receptor-mediated postsynaptic currents (NMDA PSCs) were observed between lesioned and sham operated animals. Thus, the observed perilesional changes in the NR2A/NR2B mRNA ratio appear to be subthreshold to result in significant changes in the functional properties of NMDA receptors.

Animals↗

Posterior neocortical (visual cortex) lesions in the rat impair matching-to-place navigation in a swimming pool: a reevaluation of cortical contributions to spatial behavior using a new assessment of spatial versus nonspatial behavior.

In the face of contradictory findings on the role of visual cortex contributions to spatial behavior, the present study evaluated the ability of rats with primary visual cortex (area 17) lesions to learn spatial problems in a swimming pool. Because the solution to any spatial learning problem consists of acquiring at least two primary elements of a task, task procedures and spatial learning, the study, in addition to assessing spatial ability on a place task, used two training/testing methods to identify the nature of the spatial impairment associated with visual cortex lesions. Non-spatial training consisted of learning to find a platform in the dark and spatial training consisted of a series of matching-to-place problems. The results confirmed that although rats with visual cortex lesions were impaired on place learning, the deficit was partially ameliorated by non-spatial training given following the lesion, and completely ameliorated by non-spatial training given before the lesion. Nevertheless, all visual cortex groups failed to show a quadrant preference on a probe trial and displayed a profound impairment in matching-to-place learning. This definitive demonstration that appropriate testing methods can reveal a failure in spatial behavior following visual cortex lesions is consistent with the idea that primary visual cortex is required in spatial navigation.

Animals↗

Neurons with intensely negatively charged extracellular matrix in the human visual cortex.

Neurons in the human visual cortex were demonstrated to possess an intensely negatively charged surface coat which was stained with cationic iron colloid and aldehyde fuchsin. Digestion with hyaluronidase eliminated both the iron colloid and fuchsin stainings of the coats. Treatment with chondroitinase ABC, heparitinase and keratanase eliminated the iron colloid staining of the coats, but did not interfere with the fuchsin staining. Electron microscopy of ultrathin sections revealed that the cationic iron particles were preferentially deposited in the perineuronal tissue spaces. These findings indicate that the surface coats consist of sulfated proteoglycans, which, as an extracellular matrix, occupy the perineuronal tissue spaces. This study further demonstrates that neurons with such surface coats are identical with neurons labeled with lectin Vicia villosa agglutinin. The cell surface glycoproteins reactive to this lectin may not be the structural elements of the sulfated coats since the lectin labeling was not interrupted by the hyaluronidase digestion.

Anions↗

Sex differences in the number of synaptic junctions in the binocular area of the rat visual cortex.

We had found that the binocular area of the visual cortex is larger in volume and has more neurons in male than in female rats. The present study examined whether the number of synaptic junctions in this area is sexually dimorphic. Ten littermate pairs of 90-day-old (socially housed) Long-Evans hooded rats were used. Synaptic junctions were counted and their lengths were measured on electron micrographs taken from layers II-III of the binocular visual cortex. There were no sex differences in the numerical density of synaptic junctions, the number of synaptic junctions per neuron, or the length of synaptic junctions within any synaptic category or of all synapses combined. Sex differences were found in the total number of synaptic junctions and in several categories (asymmetric synapses, spine synapses, asymmetric spine synapses): male rats had more synaptic junctions than female rats because of the larger volume of layers II-III in the binocular area of male rats. These data indicate that neurons in the binocular visual cortex of both male and female rats receive a characteristic number of synaptic junctions, but the greater number of neurons in the binocular area of male rats results in more synaptic junctions in the area.

Animals↗

Cellular organization and development of slice cultures from rat visual cortex.

Slice cultures from the visual cortex of young rats were prepared using the roller culture technique (Gähwiler 1984). After 10 days in vitro the cortical cultures flattened to 1-3 cell layers, surviving for up to 12 weeks. The cultures were organotypically organized, the typical layered structure of the cortex was preserved. The neuronal composition of slice cultures was studied using intracellular staining, Golgi impregnation and GABA immunohistochemistry. Both pyramidal cells and several types of nonpyramidal cells were identified in the slice cultures. Electrophysiological recordings showed that the electrical properties of cells in culture were similar to those measured in acute slice preparations; for some cells, however, the spontaneous activity was higher. The maintained activity was strongly increased by application of the GABA antagonist bicuculline and decreased by GABA, suggesting that GABAergic inhibition is present in these preparations. We could observe the postnatal maturation of some characteristic morphological features in culture. For example, pyramidal cells in 6 day-old rats in situ have very short basal dendrites with growth-cones, and the dendrites are free of spines. After 2-3 weeks in culture growth-cones were no longer observed. Instead, the cells had developed a large basal dendritic field and the dendrites were covered with spines. Slice cultures therefore may provide a useful tool for physiological, anatomical, pharmacological and developmental studies of cortical neurons in an organotypical environment.

Action Potentials↗

The effects of unilateral neonatal removal of visual cortex on transmitter parameters in the adult superior colliculus and lateral geniculate body.

High affinity glutamate uptake was reduced in the ipsilateral lateral geniculate body by 75% and in the ipsilateral superior colliculus by 50% one week after ablation of the visual cortex in the adult rat. Six days after neonatal removal of visual cortex, there were no effects on the high affinity glutamate uptake in these regions indicating that there were few functionally corticofugal fibres established at birth. Seventy-five days after unilateral neonatal ablation of visual cortex, the glutamate uptake in both ipsi- and contralateral superior colliculus was reduced 50% compared to unoperated controls. The glutamate uptake in the lateral geniculate body was reduced 55% ipsilateral to and 38% contralateral to the lesion. The neonatal lesion had therefore affected the development of glutamate nerve terminals bilaterally in these target regions. Destruction of the visual cortex on the unoperated side caused in these adults an additional bilateral decrease of the glutamate uptake in the superior colliculus, showing the presence of aberrant glutamatergic fibres crossing from the unoperated visual cortex. In the lateral geniculate body, a similar lesion was accompanied only by a reduction in glutamate uptake on the ipsilateral side. The neonatal ablation of visual cortex also induced small changes in glutamate decarboxylase and GABA uptake in superior colliculus 75 days after the operation.

Animals↗

Spatial frequency maps in cat visual cortex.

Neurons in the primary visual cortex (V1) respond preferentially to stimuli with distinct orientations and spatial frequencies. Although the organization of orientation selectivity has been thoroughly described, the arrangement of spatial frequency (SF) preference in V1 is controversial. Several layouts have been suggested, including laminar, columnar, clustered, pinwheel, and binary (high and low SF domains). We have reexamined the cortical organization of SF preference by imaging intrinsic cortical signals induced by stimuli of various orientations and SFs. SF preference maps, produced from optimally oriented stimuli, were verified using targeted microelectrode recordings. We found that a wide range of SFs is represented independently and mostly continuously within V1. Domains with SF preferences at the extremes of the SF continuum were separated by no more than (3/4) mm (conforming to the hypercolumn description of cortical organization) and were often found at pinwheel center singularities in the cortical map of orientation preference. The organization of cortical maps permits nearly all combinations of orientation and SF preference to be represented in V1, and the overall arrangement of SF preference in V1 suggests that SF-specific adaptation effects, found in psychophysical experiments, may be explained by local interactions within a given SF domain. By reanalyzing our data using a different definition of SF preference than is used in electrophysiological and psychophysical studies, we can reproduce the different SF organizations suggested by earlier studies.

Algorithms↗

Information tuning of populations of neurons in primary visual cortex.

Neurons in macaque primary visual cortex (V1) show a diversity of orientation tuning properties, exhibiting a broad distribution of tuning width, baseline activity, peak response, and circular variance (CV). Here, we studied how the different tuning features affect the performance of these cells in discriminating between stimuli with different orientations. Previous studies of the orientation discrimination power of neurons in V1 focused on resolving two nearby orientations close to the psychophysical threshold of orientation discrimination. Here, we developed a theoretical framework, the information tuning curve, that measures the discrimination power of cells as a function of the orientation difference, deltatheta, of the two stimuli. This tuning curve also represents the mutual information between the neuronal responses and the stimulus orientation. We studied theoretically the dependence of the information tuning curve on the orientation tuning width, baseline, and peak responses. Of main interest is the finding that narrow orientation tuning is not necessarily optimal for all angular discrimination tasks. Instead, the optimal tuning width depends linearly on deltatheta. We applied our theory to study the discrimination performance of a population of 490 neurons in macaque V1. We found that a significant fraction of the neuronal population exhibits favorable tuning properties for large deltatheta. We also studied how the discrimination capability of neurons is distributed and compared several other measures of the orientation tuning such as CV with Chernoff distances for normalized tuning curves.

Action Potentials↗

Contrast invariance of functional maps in cat primary visual cortex.

Neurons in cat primary visual cortex (V1) are clustered according to their preference for stimulus position, orientation, spatial frequency, and eye of presentation, thereby giving rise to functional maps. It is not known, however, whether a similar arrangement is present for stimulus contrast. Neurons in cat V1 vary considerably in their contrast responses, and might be clustered in a systematic fashion in this respect. Additionally, stimulus contrast might affect other functional maps. For example, there has been debate over whether the contrast threshold of neurons in cytochrome oxidase blobs is lower than elsewhere. Here we have imaged intrinsic signals to measure orientation maps in cat V1 at a range of contrast levels. We determined, on a pixel-by-pixel basis, contrast-response functions and orientation tuning curves. The fit parameters describing contrast responses were more or less uniform: We found no regions where neurons have lower contrast threshold than elsewhere. If such regions do exist, their functional maps must be substantially weaker than maps of orientation preference. Moreover, we found that contrast has no impact on maps of orientation preference: The orientation selectivity of each pixel is invariant with stimulus contrast. The contrast invariance that we demonstrate at the level of maps is well known at the level of single neurons. It suggests that neurons contributing to a pixel response generally have similar orientation preferences or similar contrast responses. The latter explanation is likely to hold in pinwheel centers, where preferred orientation of nearby neurons can differ markedly. In summary, our data suggest that contrast is represented uniformly over the surface of cat V1, and changes in contrast do not affect maps of orientation preference.

Animals↗

NMDA, AMPA, and benzodiazepine binding site changes in Alzheimer's disease visual cortex.

Quantitative receptor autoradiography was used to measure the laminar distribution of [3H]glycine and [3H]glutamate binding to the N-methyl-D-aspartate (NMDA) receptor complex, [3H]D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) binding to the AMPA receptor, and [3H]flunitrazepam binding to the benzodiazepine (BDZ) receptor in three areas of visual cortex in control and Alzheimer's disease (AD) postmortem human brains (primary or striate visual cortex, visual association cortex, and higher-order visual association cortex, corresponding to Brodmann Areas 17, 18, and 21, respectively). In Area 17, binding to the NMDA, AMPA, and BDZ receptors was not significantly altered in the AD brains (except in layer VI for [3H]glycine and layer III for [3H]AMPA, where binding was reduced in the AD brains). Ligand binding to the two EAA receptors in Area 18 was, however, significantly reduced in the AD brains (layers I through III for [3H]glycine and layers III through VI for [3H]AMPA). In Area 21, binding to both the NMDA and BDZ receptors but not to the AMPA receptor, was significantly reduced in almost all laminae of the AD brains (layers I through VI for [3H]glycine and layers I through V for [3H]flunitrazepam). This hierarchical pattern of laminar binding loss with increasing complexity of association visual cortices is consistent with the increasing numbers of neurofibrillary tangles found in those areas, implicating NMDA and BDZ receptor bearing cells in AD neuropathology. AMPA receptor losses do not parallel the pathology, suggesting that AMPA receptors are not directly correlated with the pathology.

Aged↗

Human primary visual cortex topography imaged via positron tomography.

The visuotopic structure of primary visual cortex was studied in a group of 7 human volunteers using positron emission transaxial tomography (PETT) and 18F-labeled 2-deoxy-2-fluoro-D-glucose ( [18F]DG). A computer animation was constructed with a spatial structure which was matched to estimates of human cortical magnification factor and to striate cortex stimulus preferences. A lateralized cortical 'checker-board' pattern of [18F]DG was stimulated in primary visual cortex by having subjects view this computer animation following i.v. injection of [18F]DG. The spatial structure of the stimulus was designed to produce an easily recognizable 'signature' in a series of 9 serial PETT scans obtained from each of a group of 7 volunteers. The predicted lateralized topographic 'signature' was observed in 6 of 7 subjects. Applications of this method for further PETT studies of human visual cortex are discussed.

Deoxyglucose↗

Neural mechanisms of spatial selective attention in areas V1, V2, and V4 of macaque visual cortex.

Many neurons in extrastriate visual cortex have large receptive fields, and this may lead to significant computational problems whenever multiple stimuli fall within a single field. Previous studies have suggested that when multiple stimuli fall within a cell's receptive field, they compete for the cell's response in a manner that can be biased in favor of attended stimuli. In the present study we examined this role of attention in areas V1, V2, and V4 of macaque monkeys with the use of a behavioral paradigm in which attention was directed to one of two stimulus locations. When two stimuli were presented simultaneously inside the cell's receptive field (which could be accomplished only in areas V2 and V4), we found that the cell's response was strongly influenced by which of the two stimuli was attended. The size of this attention effect was reduced when the attended and ignored stimuli were presented sequentially rather than simultaneously. In addition, the effects became very weak and inconsistent in these areas when only one of the two stimuli was located inside the receptive field. Attention thus modulated sensory responses primarily when two or more simultaneous stimuli competed for access to a neuron's receptive field. As in areas V2 and V4, attention did not modulate sensory responses in area V1 when only a single stimulus was inside the receptive field. In addition, the small receptive fields in this area precluded the simultaneous presentation of attended and ignored stimuli inside the receptive field, making it impossible to determine whether attention effects would be observed under the conditions that led to consistent attention effects in areas V2 and V4. Spontaneous firing rates in areas V2 and V4 were found to be 30-40% higher when attention was directed inside rather than outside the receptive field, even when no stimulus was present in the receptive field. Spontaneous firing rates also varied according to the particular location within the receptive field that was attended. These shifts in spontaneous activity may reflect a top-down signal that biases responses in favor of stimuli at the attended location.

Animals↗

Prediction of the main cortical areas and connections involved in the tactile function of the visual cortex by network analysis.

We explored the cortical pathways from the primary somatosensory cortex to the primary visual cortex (V1) by analysing connectional data in the macaque monkey using graph-theoretical tools. Cluster analysis revealed the close relationship of the dorsal visual stream and the sensorimotor cortex. It was shown that prefrontal area 46 and parietal areas VIP and 7a occupy a central position between the different clusters in the visuo-tactile network. Among these structures all the shortest paths from primary somatosensory cortex (3a, 1 and 2) to V1 pass through VIP and then reach V1 via MT, V3 and PO. Comparison of the input and output fields suggested a larger specificity for the 3a/1-VIP-MT/V3-V1 pathways among the alternative routes. A reinforcement learning algorithm was used to evaluate the importance of the aforementioned pathways. The results suggest a higher role for V3 in relaying more direct sensorimotor information to V1. Analysing cliques, which identify areas with the strongest coupling in the network, supported the role of VIP, MT and V3 in visuo-tactile integration. These findings indicate that areas 3a, 1, VIP, MT and V3 play a major role in shaping the tactile information reaching V1 in both sighted and blind subjects. Our observations greatly support the findings of the experimental studies and provide a deeper insight into the network architecture underlying visuo-tactile integration in the primate cerebral cortex.

Algorithms↗