Direct mapping of ocular dominance columns in human primary visual cortex

Functional magnetic resonance imaging at 2.0T was employed to identify columnar structures in human visual cortex. Sagittal sections (4 mm thickness) covering the calcarine cortex were acquired with use of a multiecho low flip angle gradient-echo sequence at 4.0 s temporal resolution and 0.25 x 0.25 mm2 spatial resolution. Extending earlier attempts based on a differential paradigm contrasting left vs right eye stimulation, this work presents the first direct mapping of human ocular dominance columns by measuring separate activation maps with left and right eye stimulation. The resulting individual maps reveal patterns of ocular dominance as spots or bands of altered activity in calcarine cortex. Their superposition shows only little spatial overlap of eye-specific encoding which strongly supports the genuineness of these functional units.     

The overall pattern of ocular dominance bands in cat visual cortex

This study describes the overall arrangement of geniculocortical input representing the system of cortical ocular dominance bands in layer IV of striate cortex in the adult cat. The pattern of ocular dominance bands was revealed by transneuronal transport of the intraocularly injected tracer wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Our data indicate that this procedure does not damage the retina and that it results in relatively uniform uptake and transport of the tracer. Using previously published techniques (Olavarria and Van Sluyters, 1983, 1985), both cortical hemispheres of each cat were unfolded, flattened and tangentially sectioned. Analysis of the WGA-HRP labeling patterns in these sections revealed a relatively continuous network of irregularly branching bands in layer IV of area 17 in both hemispheres. Because of a systematic difference in the level of interband labeling, ocular dominance bands appear less distinct in the hemisphere contralateral to the injected eye. There is also a tendency for interband labeling to be greater in cortical regions that represent the more peripheral aspects of the binocular portion of the visual field. The width of an individual ocular dominance band in the cat fluctuates, so that it appears to be made up of a series of uniformly sized, roughly circular beads of label. The diameter of these beads averages 667 micron, and preliminary counts indicate that there are 650-675 beads in each striate cortex. Contrary to earlier suggestions, in 4 out of 6 hemispheres analyzed quantitatively there was no tendency for ocular dominance bands to be oriented along a preferred axis in cat striate cortex, including an axis orthogonal to the border between areas 17 and 18. Ocular dominance bands in area 18 appear to be broader than those in area 17, and they seem to have a greater tendency to be oriented orthogonal to the 17/18 border than those in area 17. Compared with the ocular dominance pattern in monkey striate cortex, the ocular dominance pattern in the cat is much less regular. In general, cat ocular dominance bands appear to fluctuate more in width, to change direction more often, and to be less likely to run orthogonal to the 17/18 border. The greater regularity of the primate ocular dominance pattern may be related to differences in the way in which the visual hemifield is mapped onto the striate cortex in these 2 species.     

Experience-dependent reactivation of ocular dominance plasticity in the adult visual cortex

A crucial issue in neurobiology is to understand the main mechanisms restricting neural plasticity to brief windows of early postnatal life. The visual system is one of the paradigmatic models for studying experience-dependent plasticity. The closure of one eye (monocular deprivation, MD) causes a marked ocular dominance (OD) shift of neurons in the primary visual cortex only during the critical period. Here, we report that environmental enrichment (EE), a condition of increased sensory-motor stimulation, reactivates OD plasticity in the adult visual cortex, as assessed with both visual evoked potentials and single-unit recordings. This effect is accompanied by a marked increase in cerebral serotonin (5-HT) levels. Blocking 5-HT enhancement in the visual cortex of EE rats completely prevents the OD shift induced by MD. We also found that EE leads to a reduced intracortical GABAergic inhibition and an increased BDNF expression and that the modulation of these molecular factors is neutralized by cortical infusion of the 5-HT synthesis inhibitor pCPA. Our results show that EE rejuvenates the adult visual cortex and that 5-HT is a crucial factor in this process, triggering a cascade of molecular events that allow the reinstatement of neural plasticity. The non-invasive nature of EE makes this paradigm particularly eligible for clinical application.     

Structure and function relationships during ocular dominance plasticity in the visual cortex

Our ability to learn relies on the potential of the neocortex to change its neuronal circuits through experience. This change is mediated by the loss or formation of synaptic contacts or the adjustment of their synaptic strength. In recent decades, the primary visual cortex has proven an excellent system for studying structure/function relationships during plasticity in the neocortex. Here we describe current knowledge about the structural changes in inhibitory or excitatory synapses that accompany experience dependent plasticity in the visual cortex. We discuss unresolved issues and technical developments that will help to provide answers in the near future.     

Noradrenergic control of ocular dominance plasticity in the visual cortex of dark-reared cats

In the visual cortex of cats which had been dark-reared for several months since the time before natural eye opening, a cortical infusion of 6-hydroxydopamine (6-OHDA), a noradrenaline (NA)-related neurotoxin, partially suppressed a usual shift in ocular dominance following brief monocular lid suture, causing a significant loss of binocular cells. This partial shift in ocular dominance (U-shaped histogram) was also observed typically in the control hemisphere of cats which were subjected to dark-rearing for more than a year. Furthermore, the expected shift in ocular dominance following monocular deprivation was blocked by a direct cortical infusion of D,L-metoprolol, a selective beta 1-adrenergic receptor antagonist. The blockade was not obtained by D-metoprolol, a biologically inert stereo-isomer, under the comparable condition. In contrast, exogenous L-NA gave rise to an obvious shift in ocular dominance toward the non-deprived eye. The present results suggest that the NA-beta 1 adrenoreceptor system was necessary to maintain the ocular dominance plasticity in the visual cortex of dark-reared cats.     

Early postnatal development of functional ocular dominance columns in cat primary visual cortex

During postnatal development of the visual cortex the thalamocortical afferents serving the two eyes segregate into alternating patches called ocular dominance (OD) columns. Interested in the dynamics of this segregation process we studied the appearance of functional OD columns in the primary visual cortex of normally raised and strabismic kittens aged 2-6 weeks using 2-deoxyglucose labelling in awake animals. In both experimental groups, OD columns covering the entire area 17 and spanning all cortical laminae are first visible at 3 weeks and appear already adult-like at 4 weeks, much earlier than thought on the basis of previous anatomical studies. We hypothesize that a small and anatomically undetectable imbalance between the afferents from the two eyes is amplified by intracortical interactions so that their activity patterns become different and may guide the segregation process of the afferents in cortical layer IV.     

Ocular dominance in anterior visual cortex in a child demonstrated by the use of fMRI

Negative signal changes in the visual cortex have been observed during visual stimulation when performing functional magnetic resonance imaging (fMRI) in children. This report investigated whether the ocular dominance, which has been demonstrated in the contralateral anterior visual cortex in adults, could be observed in a child by the use of fMRI. A 5-year-old child was studied using fMRI at 1.5 T during alternating monocular visual stimulation under sedation with morphine and pentobarbital. The functional images were motion corrected, and statistical parametric maps were made by contrasting the left or right eye stimulation conditions vs the right or left eye stimulation conditions, respectively, at each voxel. Areas with negative signal changes were found on the left anterior visual cortex during monocular visual stimulation of the right eye and vice versa. There was no area with negative or positive signal change on the ipsilateral visual cortex to the stimulated eye and no area with positive signal change on the contralateral visual cortex. Contralateral ocular dominance of anterior visual cortex similar to that of adults was demonstrated in this child with a negative correlation with the visual stimulus. This finding suggests that peripheral visual fields are represented in the anterior visual cortex of 5-year-old children.     

Emergence of ocular dominance columns in cat visual cortex by 2 weeks of age

Previous anatomic studies of the geniculocortical projection showed that ocular dominance columns emerge by 3 weeks of age in cat visual cortex, but recent optical imaging experiments have revealed a pattern of physiologic eye dominance by the end of the second week of life. We used two methods to search for an anatomic correlate of this early functional ocular dominance pattern. First, retrograde labeling of lateral geniculate nucleus (LGN) inputs to areas of cortex preferentially activated by one eye showed that the geniculocortical projection was already partially segregated by eye at postnatal day 14 (P14). Second, transneuronal label of geniculocortical afferents in flattened sections of cortex after a tracer injection into one eye showed a periodic pattern at P14 but not at P7. In the classic model for the development of ocular dominance columns, initially overlapping geniculocortical afferents segregate by means of an activity-dependent competitive process. Our data are consistent with this model but suggest that ocular dominance column formation begins between P7 and P14, approximately a week earlier than previously believed. The functional and anatomic data also reveal an early developmental bias toward contralateral eye afferents. This initial developmental bias is not consistent with a strictly Hebbian model for geniculocortical afferent segregation. The emergence of ocular dominance columns before the onset of the critical period for visual deprivation also suggests that the mechanisms for ocular dominance column formation may be partially distinct from those mediating plasticity later in life.     

Coincidence of ipsilateral ocular dominance peaks with orientation pinwheel centers in cat visual cortex

Geometrical relationships among multiple cortical maps, such as those between ocular dominance and orientation maps, are a prominent feature of the brain's functional architecture. It is also well known that there is a strong bias of cortical responses toward the contralateral eye during early postnatal development. We wondered therefore whether and how such an imbalance of cortical responsiveness in a developing animal might influence the mutual geometrical relationships between orientation and ocular dominance maps in adult animals. The results of our study indicate the existence of a strong tendency for the peaks of the ipsilateral eye domains to coincide with the location of point singularities (pinwheel centers) in orientation maps. No such relationship was found for the peaks of contralateral eye domains. Computational studies reproduced similar asymmetry in the coincidence under the contralateral eye bias of inputs. Our study raised the idea that the pinwheel centers play an important role for retaining the weaker ipsilateral eye inputs during normal development.     

Organization of ocular dominance in tree shrew striate cortex.

In the process of an extensive Golgi analysis of the inferior region of the rat hippocampus, a hitherto undescribed cell type was discovered. The cell has a round, elliptical, or fusiform cell body and an apical dendritic plume reminiscent of dentate granule cells. The axon is thick, with many collateral and ramifies within, above and below the pyramidal layer. The proximal dendrites have stubby spines whereas the distal dendrites have long thin spines. All impregnated cells of this type were found in the inferior region (CA₃ and CA₄ of Lorente de No´) of the hippocampus and most were found in a circumscribed suprapyramidal region at the mouth of the hilus. The majority of impregnated cells of this type were found in the middle to temporal portion of the hippocampus. Nissl-stained sections confirmed the predominant occurence of this cell type in the inferior region of the middle to temporal hippocampus. In these preparations, the cells have a large nucleus, several nucleoli and very scanty cytoplasm with Nissl substance essentially confined to the initial dendritic segments. The unique morphology of this cell type allows relatively easy identification using Nissl staining.     

Right hemispheric dominance of visual phenomena evoked by intracerebral stimulation of the human visual cortex

Electrical brain stimulation can provide important information about the functional organization of the human visual cortex. Here, we report the visual phenomena evoked by a large number (562) of intracerebral electrical stimulations performed at low‐intensity with depth electrodes implanted in the occipito‐parieto‐temporal cortex of 22 epileptic patients. Focal electrical stimulation evoked primarily visual hallucinations with various complexities: simple (spot or blob), intermediary (geometric forms), or complex meaningful shapes (faces); visual illusions and impairments of visual recognition were more rarely observed. With the exception of the most posterior cortical sites, the probability of evoking a visual phenomenon was significantly higher in the right than the left hemisphere. Intermediary and complex hallucinations, illusions, and visual recognition impairments were almost exclusively evoked by stimulation in the right hemisphere. The probability of evoking a visual phenomenon decreased substantially from the occipital pole to the most anterior sites of the temporal lobe, and this decrease was more pronounced in the left hemisphere. The greater sensitivity of the right occipito‐parieto‐temporal regions to intracerebral electrical stimulation to evoke visual phenomena supports a predominant role of right hemispheric visual areas from perception to recognition of visual forms, regardless of visuospatial and attentional factors. Hum Brain Mapp 35:3360–3371, 2014. © 2013 Wiley Periodicals, Inc .     

The relationship between relative eye usage and ocular dominance shifts in cat visual cortex

A novel modification of the alternate monocular deprivation paradigm was used to quantitatively define the relationship between relative eye usage and the shift in visual cortical ocular dominance toward the advantaged eye. Both eyes of cats were alternately occluded by contact lenses during daily visual exposure sessions with varying ratios of relative eye usage: 1:1, 1.7:1, 3:1, 7:1, 50:1, 100:0. Only 100:0 and 50:1 ratios produced an ocular dominance shift in favor of the more experienced eye. The ocular dominance shift in 100:0 cats occurred in all cortical layers but only in extragranular layers of 50:1 cats. A steep power function described the data, indicating that an extreme imbalance in relative eye usage (>90%) is required for an ocular dominance shift.     

Development and organization of ocular dominance bands in primary visual cortex of the sable ferret

Thalamocortical afferents in the visual cortex of the adult sable ferret are segregated into eye-specific ocular dominance bands. The development of ocular dominance bands was studied by transneuronal labeling of the visual cortices of ferret kits between the ages of postnatal day 28 (P28) and P81 after intravitreous injections of either tritiated proline or wheat germ agglutinin-horseradish peroxidase. Laminar specificity was evident in the youngest animals studied and was similar to that in the adult by P50. In P28 and P30 ferret kits, no modulation reminiscent of ocular dominance bands was detectable in the pattern of labeling along layer IV. By P37 a slight fluctuation in the density of labeling in layer IV was evident in serial reconstructions. By P50, the amplitude of modulation had increased considerably but the pattern of ocular dominance bands did not yet appear mature. The pattern and degree of modulation of the ocular dominance bands resembled that in adult animals by P63. Flat mounts of cortex and serial reconstructions of layer IV revealed an unusual arrangement of inputs serving the two eyes in the region rostral to the periodic ocular dominance bands. In this region, inputs serving the contralateral eye were commonly fused along a mediolateral axis, rostral to which were large and sometimes fused patches of ipsilateral input.     

Differential effects of neurotrophins on ocular dominance plasticity in developing and adult cat visual cortex

In the present study we examine the influence of neurotrophins on experience-dependent synaptic rearrangement in developing and adult visual cortex. Brain-derived neurotrophic factor (BDNF) or nerve growth factor (NGF) was continuously infused into cortical area 18, and the functional architecture of the cortex was examined by use of optical and electrophysiological recording techniques. In kittens, BDNF infusion during monocular deprivation (MD) reversed the normally occurring ocular dominance (OD) shift towards the non-deprived eye so that the deprived eye dominated the BDNF-treated cortex after MD. Under conditions of equal activation of thalamocortical synapses, i.e. when animals were either subject to binocular deprivation (BD) or reared without deprivation, BDNF infusion did not disrupt binocularity of cortical units, but reversed the natural OD bias towards the contralateral eye in favour of the ipsilateral eye. In addition, BDNF treatment in kittens led to a loss of the orientation selectivity of cortical units irrespective of rearing conditions. In adult animals, BDNF influenced neither OD distributions nor orientation selectivity. The effect of NGF was markedly different. It was ineffective in kittens but in adult animals it caused a shift of OD towards the deprived eye when MD was combined with NGF infusion. However, in this case orientation selectivity was preserved. Thus, both neurotrophins have profound activity- and age-dependent effects on the functional architecture of the visual cortex. Moreover, our results indicate that simple substitution of neurotrophins in excess is unlikely to compensate for deprivation effects by preserving or restoring the normal functional architecture of the cortex.     

Identifying human parieto-insular vestibular cortex using fMRI and cytoarchitectonic mapping

The parieto-insular vestibular cortex (PIVC) plays a central role in the cortical vestibular network. Although this region was first defined and subsequently extensively studied in nonhuman primates, there is also ample evidence for a human analogue in the posterior parietal operculum. In this study, we functionally and anatomically characterize the putative human equivalent to macaque area PIVC by combining functional magnetic resonance imaging (fMRI) of the cortical response to galvanic vestibular stimulation (GVS) with probabilistic cytoarchitectonic maps of the human parietal operculum. Our fMRI data revealed a bilateral cortical response to GVS in posterior parieto-insular cortex. Based on the topographic similarity of these activations to primate area PIVC, we suggest that they constitute the functionally defined human equivalent to macaque area PIVC. The locations of these activations were then compared to the probabilistic cytoarchitectonic maps of the parietal operculum (Eickhoff et al. [2005a]: Cereb Cortex, in press; Eickhoff et al. [2005c]: Cereb Cortex, in press), whereby the functionally defined PIVC matched most closely the cytoarchitectonically defined area OP 2. This activation of OP 2 by vestibular stimulation and its cytoarchitectonic features, which are similar to other primary sensory areas, suggest that area OP 2 constitutes the human equivalent of macaque area PIVC.     

Direction-dependent visual cortex activation during horizontal optokinetic stimulation (fMRI study)

Looking at a moving pattern induces optokinetic nystagmus (OKN) and activates an assembly of cortical areas in the visual cortex, including lateral occipitotemporal (motion-sensitive area MT/V5) and adjacent occipitoparietal areas as well as ocular motor areas such as the prefrontal cortex, frontal, supplementary, and parietal eye fields. The aim of this functional MRI (fMRI) study was to investigate (1) whether stimulus direction-dependent effects can be found, especially in the cortical eye fields, and (2) whether there is a hemispheric dominance of ocular motor areas. In a group of 15 healthy subjects, OKN in rightward and leftward directions was visually elicited and statistically compared with the control condition (stationary target) and with each other. Direction-dependent differences were not found in the cortical eye fields, but an asymmetry of activation occurred in paramedian visual cortex areas, and there were stronger activations in the hemisphere contralateral to the slow OKN phase (pursuit). This can be explained by a shift of the mean eye position of gaze (beating field) in the direction of the fast nystagmus phases of approximately 2.6 degrees, causing asymmetrical visual cortex stimulation. The absence of a significant difference in the activation pattern of the cortical eye fields supports the view that the processing of eye movements in both horizontal directions is mediated in the same cortical ocular motor areas. Furthermore, no hemispheric dominance for OKN processing was found in right-handed volunteers.     

The pattern of ocular dominance columns in macaque visual cortex revealed by a reduced silver stain

A pattern of alternative dark and pale bands was observed in the straite cortex of the macaque monkey. The bands, which ran parallel to the surface, were seen in tangential sections stained with a reduced silver method for normal fibers and were most clear in layer 4C α, immediately deep to the line of Gennari. The dark bands were about 300 μ wide and showed blind endings and bifurcations. The light bands were about 50 μ wide and did not branch or terminate within area 17. Because the dark bands were similar in width to the bands of terminal degeneration which have been shown to result from single-layer lesions of the lateral geniculate body, it seemed possible that they corresponded to ocular dominance columns. To test this idea, the boundaries of ocular dominance columns were marked in a physiological experiment: tangential electrode penetrations were made in an anesthetized monkey and, as the electrode was advanced horizontally in the fourth layer, the eye preference of single units and of the background activity was monitored. Small electrolytic lesions were placed at the points where a change in eye preference occurred. The brain was subsequently fixed, sectioned tangentially and stained with the silver method. All the lesions — a total of 12 — fell directly on the pale bands. Moreover, the electrode had not passed over any pale bands without a lesion being placed. It was concluded that the dark bands do correspond to single ocular dominance columns and the pale bands to the boundaries between columns. The banding appearance is due to a greater density of tangential fibers within columns than at the borders of columns. These tangential fibers are in part the preterminal arborizations of geniculocortical axons, since some of them have been shown to degenerate after geniculate lesion. The ocular dominance columns were mapped for most of the striate cortex, using serial tengential sections stained with the silver method. The overall pattern was similar in several monkeys, though the details of the branching arrangements vaired from animal to animal. The columns met the 17–18 border at rigtht angles. On the outer surface of the hemisphere the columns converged from the 17–18 border, turned medially with repeated fusions of columns, and streamed over the lip of the calcarine fissure. In the roof of the fissure they met a second system of columns oriented parasagittally. In terms of the visual field, the columns ran roughly horizontally for the central 10° of the field, and circumferentially beyond that. The columns were not mapped in the stem of the fissure, the area corresponding to the far periphery of the field. The constancy of column width across the cortex probably allows a functional matching between ocular-dominance and orientation columns.     

Multi-modality mapping of motor cortex: comparing echoplanar BOLD fMRI and transcranial magnetic stimulation

Summary Multiple non-invasive methods of imaging brain function are now available for presurgical planning and neurobiological research. As these new methods become available, it is important to understand their relative advantages and liabilities, as well as how the information gained compares across different methods. A current and future trend in neurobiological studies as well as presurgical planning is to combine information from different imaging techniques. Multi-modal integration may perhaps give more powerful information than each modality alone, especially when one of the methods is transcranial magnetic stimulation (TMS), with its ability to non-invasively activate the brain. As an initial venture in cross comparing new imaging methods, we performed the following 2 studies, locating motor cortex with echoplanar BOLD fMRI and TMS. The two methods can be readily integrated, with concurring results, although each have important limitations.