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Diplopia (double vision) in strabismus is prevented by suppression of the image emanating from one eye. In a recent study conducted in two macaques raised with exotropia (an outward ocular deviation) but having normal acuity in each eye, simultaneous display of stimuli to each eye did not induce suppression in V1 neurons. Puzzled by this negative result, we have modified our protocol to display stimuli in a staggered sequence, rather than simultaneously. Additional recordings were made in the same two macaques, following two paradigms. In trial type 1, the receptive field in one eye was stimulated with a sine-wave grating while the other eye was occluded. After 5 s, the occluder was removed and the neuron was stimulated for another 5 s. The effect of uncovering the eye, which potentially exposed the animal to diplopia, was quantified by the peripheral retinal interaction index (PRII). In trial type 2, the receptive field in the fixating eye was stimulated with a grating during binocular viewing. After 5 s, a second grating appeared in the receptive field of the nonfixating eye. The impact of the second grating, which had the potential to generate visual confusion, was quantified by the receptive field interaction index (RFII). For 82 units, the mean PRII was 0.48 ± 0.05 (0.50 = no suppression) and the mean RFII was 0.46 ± 0.08 (0.50 = no suppression). These values suggest mild suppression, but the modest decline in spike rate registered during the second epoch of visual stimulation might have been due to neuronal adaptation, rather than interocular suppression. In a few instances neurons showed unequivocal suppression, but overall, these recordings did not support the contention that staggered stimulus presentation is more effective than simultaneous stimulus presentation at evoking interocular suppression in V1 neurons. NEW & NOTEWORTHY In strabismus, double vision is prevented by interocular suppression. It has been reported that inhibition of neuronal firing in the primary visual cortex occurs only when stimuli are presented sequentially, rather than simultaneously. However, these recordings in alert macaques raised with exotropia showed, with rare exceptions, little evidence to support the concept that staggered stimulus presentation is more effective at inducing interocular suppression of V1 neurons.

When similar visual stimuli are presented binocularly to both eyes, one perceives a fused single image. However, when the two stimuli are distinct, one does not perceive a single image; instead, one perceives binocular rivalry. That is, one perceives one of the stimulated patterns for a few seconds, then the other for few seconds, and so on - with random transitions between the two percepts. Most theoretical studies focus on rivalry, with few considering the coexistence of fusion and rivalry. Here we develop three distinct computational neuronal network models which capture binocular rivalry with realistic stochastic properties, fusion, and the hysteretic transition between. Each is a conductance-based point neuron model, which is multi-layer with two ocular dominance columns (L & R) and with an idealized "ring" architecture where the orientation preference of each neuron labels its location on a ring. In each model, the primary mechanism initiating binocular rivalry is cross-column inhibition, with firing rate adaptation governing the temporal properties of the transitions between percepts. Under stimulation by similar visual patterns, each of three models uses its own mechanism to overcome cross-column inhibition, and thus to prevent rivalry and allow the fusion of similar images: The first model uses cross-column feedforward inhibition from the opposite eye to "shut off" the cross-column feedback inhibition; the second model "turns on" a second layer of monocular neurons as a parallel pathway to the binocular neurons, rivaling out of phase with the first layer, and together these two pathways represent fusion; and the third model uses cross-column excitation to overcome the cross-column inhibition and enable fusion. Thus, each of the idealized ring models depends upon a different mechanism for fusion that might emerge as an underlying mechanism present in real visual cortex.

Eye dominance refers to the preference to use one eye more than the fellow eye to accomplish a task. However, the dominant eye revealed can be task dependent especially when the tasks are as diverse as instructing the observer to sight a target through a ring, or to report which half-image is perceived more of during binocular rivalry stimulation. Conventionally, the former task is said to reveal motor eye dominance while the latter task reveals sensory eye dominance. While the consensus is that the motor and sensory-dominant eye could be different in some observers, the reason for it is still unclear and has not been much researched. This review mainly focuses on advances made in recent studies of sensory eye dominance. It reviews studies conducted to quantify and relate sensory eye dominance to other visual functions, in particular to stereopsis, as well as studies conducted to explore its plasticity. It is recognized that sensory eye dominance in observers with clinically normal vision shares some similarity with amblyopia at least at the behavioral level, in that both exhibit an imbalance of interocular inhibition. Furthermore, sensory eye dominance is probably manifested at multiple sites along the visual pathway, perhaps including the level of ocular dominance columns. But future studies with high-resolution brain imaging approaches are required to confirm this speculation in the human visual system.

Mapping mesoscopic cortical functional units such as columns or laminae is increasingly pursued by ultra-high field (UHF) functional magnetic resonance imaging (fMRI). The most popular approach for high-resolution fMRI is currently gradient-echo (GE) blood oxygenation level-dependent (BOLD) fMRI. However, its spatial accuracy is reduced due to its sensitivity to draining vessels, including pial veins, whereas spin-echo (SE) BOLD signal is expected to have higher spatial accuracy, albeit with lower sensitivity than the GE-BOLD signal. Here, we introduce a new double spin-echo (dSE) echo-planar imaging (EPI) method to improve the sensitivity of SE-BOLD contrast by averaging two spin-echoes using three radiofrequency pulses. Human fMRI experiments were performed with slices perpendicular to the central sulcus between motor and sensory cortices at 7 T during fist-clenching with touching. First, we evaluated the feasibility of single-shot dSE-EPI for BOLD fMRI with 1.5 mm isotropic resolution and found that dSE-BOLD fMRI has higher signal-to-noise ratio (SNR), temporal SNR (tSNR), and higher functional sensitivity than conventional SE-BOLD fMRI. Second, to investigate the laminar specificity of dSE-BOLD fMRI, we implemented a multi-shot approach to achieve 0.8-mm isotropic resolution with sliding-window reconstruction. Unlike GE-BOLD fMRI, the cortical profile of dSE-BOLD fMRI peaked at ~ 1.0 mm from the surface of the primary motor and sensory cortices, demonstrating an improvement of laminar specificity in humans over GE-BOLD fMRI. The proposed multi-shot dSE-EPI method is viable for high spatial resolution UHF-fMRI studies in the pursuit of resolving mesoscopic functional units.

Because at least some squirrel monkeys lack ocular dominance columns (ODCs) in the striate cortex (V1) that are detectable by cytochrome oxidase (CO) histochemistry, the functional importance of ODCs on stereoscopic 3-D vision has been questioned. However, conventional CO histochemistry or trans-synaptic tracer study has limited capacity to reveal cortical functional architecture, whereas the expression of immediate-early genes (IEGs), c-FOS and ZIF268, is more directly responsive to neuronal activity of cortical neurons to demonstrate ocular dominance (OD)-related domains in V1 following monocular inactivation. Thus, we wondered whether IEG expression would reveal ODCs in the squirrel monkey V1. In this study, we first examined CO histochemistry in V1 of five squirrel monkeys that were subjected to monocular enucleation or tetrodotoxin (TTX) treatment to address whether there is substantial cross-individual variation as reported previously. Then, we examined the IEG expression of the same V1 tissue to address whether OD-related domains are revealed. As a result, staining patterns of CO histochemistry were relatively homogeneous throughout layer 4 of V1. IEG expression was also moderate and homogeneous throughout layer 4 of V1 in all cases. On the other hand, the IEG expression was patchy in accordance with CO blobs outside layer 4, particularly in infragranular layers, although they may not directly represent OD clusters. Squirrel monkeys remain an exceptional species among anthropoid primates with regard to OD organization, and thus are potentially good subjects to study the development and function of ODCs.

Callosal patches in primary visual cortex of Long Evans rats, normally associated with ocular dominance columns, emerge by postnatal day 10 (P10), but they do not form in rats monocularly enucleated a few days before P10. We investigated whether we could replicate the results of monocular enucleation by using tetrodotoxin (TTX) to block neural activity in one eye, or in primary visual cortex. Animals received daily intravitreal (P6–P9) or intracortical (P7–P9) injections of TTX, and our physiological evaluation of the efficacy of these injections indicated that the blockade induced by a single injection lasted at least 24 h. Four weeks later, the patterns of callosal connections in one hemisphere were revealed after multiple injections of horseradish peroxidase in the other hemisphere. We found that in rats receiving either intravitreal or cortical injections of TTX, the patterns of callosal patches analyzed in tangential sections from the flattened cortex were not significantly different from the pattern in normal rats. Our findings, therefore, suggest that the effects of monocular enucleation on the distribution of callosal connections are not due to the resulting imbalance of afferent ganglion cell activity, and that factors other than neural activity are likely involved.

Physiologically based neural field theory (NFT) is extended to encompass cortical plasticity dynamics. An illustrative application is provided which treats the evolution of the connectivity of left- and right-eye visual stimuli to neuronal populations in the primary visual cortex (V1), and the initial, linear phase of formation of approximately one-dimensional (1D) ocular dominance columns (ODCs) that sets their transverse spatial scale. This links V1 activity, structure, and physiology within a single theory that already accounts for a range of other brain activity and connectivity phenomena, thereby enabling ODC formation and many other phenomena to be interrelated and cortical parameters to be constrained across multiple domains. The results accord with experimental ODC widths for realistic cortical parameters and are based directly on a unified description of the neuronal populations involved, their connection strengths, and the neuronal activity they support. Other key results include simple analytic approximations for ODC widths and the parameters of maximum growth rate, constraints on cortical excitatory and inhibitory gains, elucidation of the roles of specific poles of the V1 response function, and the fact that ODCs are not formed when input stimuli are fully correlated between eyes. This work provides a basis for further generalization of NFT to model other plasticity phenomena, thereby linking them to the range multiscale phenomena accounted for by NFT.

Columns and layers are fundamental organizational units of the brain. Well known examples of cortical columns are the ocular dominance columns (ODCs) in primary visual cortex and the column-like stripe-based arrangement in the second visual area V2.\ud \ud The spatial scale of columns and layers is beyond the reach of conventional neuroimaging, but the advent of high field magnetic resonance imaging (MRI) scanners (UHF, 7 Tesla and above) has opened the possibility to acquire data at this spatial scale, in-vivo and non-invasively in humans.\ud \ud The most prominent non-invasive technique to measure brain function is blood oxygen level dependent (BOLD) fMRI, measuring brain activity indirectly, via changes in hemodynamics. A key determinant of the ability of high-resolution BOLD fMRI to accurately resolve columns and layers is the point-spread function (PSF) of the BOLD response in relation to the spatial extent of neuronal activity.\ud \ud In this study we take advantage of the stripe-based arrangement present in visual area V2, coupled with sub-millimetre anatomical and gradient-echo BOLD (GE BOLD) acquisition at 7 T to obtain PSF estimates and along cortical depth in human participants.\ud \ud Results show that the BOLD PSF is maximal in the superficial part of the cortex (1.78 mm), and it decreases with increasing cortical depth (0.83 mm close to white matter).

Contains fulltext : 221628.pdf (Publisher’s version ) (Closed access) The cortex is a massively recurrent network, characterized by feedforward and feedback connections between brain areas as well as lateral connections within an area. Feedforward, horizontal and feedback responses largely activate separate layers of a cortical unit, meaning they can be dissociated by lamina-resolved neurophysiological techniques. Such techniques are invasive and are therefore rarely used in humans. However, recent developments in high spatial resolution fMRI allow for non-invasive, in vivo measurements of brain responses specific to separate cortical layers. This provides an important opportunity to dissociate between feedforward and feedback brain responses, and investigate communication between brain areas at a more fine- grained level than previously possible in the human species. In this review, we highlight recent studies that successfully used laminar fMRI to isolate layer-specific feedback responses in human sensory cortex. In addition, we review several areas of cognitive neuroscience that stand to benefit from this new technological development, highlighting contemporary hypotheses that yield testable predictions for laminar fMRI. We hope to encourage researchers with the opportunity to embrace this development in fMRI research, as we expect that many future advancements in our current understanding of human brain function will be gained from measuring lamina-specific brain responses. 7 p.

Lattice-like patterns in layer 1 (L1) of primary visual cortex (V1) of mice have been demonstrated following injections of tracers into the lateral geniculate nucleus (LGN) of the thalamus (Ji et al., 2015). To distinguish the ipsilateral and contralateral components of this projection, we made unilateral intravitreal injections of the transneuronal tracer WGA-HRP in Long Evans rats, a strain in which projections to L4 form ocular dominance columns (ODCs, Laing et al., 2015). We have shown that ODCs form by postnatal day 10 (P10), and that they are susceptible to monocular enucleation and monocular deprivation by eyelid suture during development (Olavarria et al., 2021). We now show that lattice-like patterns in L1 are also visible by P10, but unlike the normal contralateral projection to L4, which does not encroach into ipsilateral eye territory, the contralateral projections to layer 1 in P10 and adult normal rats are distributed throughout V1, including ipsilateral eye territories. Moreover, this pattern does not change in visually deprived rats, suggesting that L1 projections are not susceptible to visual deprivation as L4 projections are. Notably, contralateral projections to L4 in visually deprived rats do encroach into ipsilateral eye territory, resembling the projection pattern in L1. Together, these observations suggest that geniculate projections to L1 or L4 differ not only in the cues guiding their target selection, but also in cues determining their distribution within V1, and the way they respond to visual deprivation during development.

Ultra-high field MRI can functionally image the cerebral cortex of human subjects at the submillimeter scale of cortical columns and laminae. Here, we investigate both in concert, by imaging ocular dominance columns (ODCs) in primary visual cortex (V1) across different cortical depths. We ensured that putative ODC patterns in V1 (a) are stable across runs, sessions, and scanners located in different continents, (b) have a width (~1.3 mm) expected from post-mortem and animal work and (c) are absent at the retinotopic location of the blind spot. We then dissociated the effects of bottom-up thalamo-cortical input and attentional feedback processes on activity in V1 across cortical depth. Importantly, the separation of bottom-up information flows into ODCs allowed us to validly compare attentional conditions while keeping the stimulus identical throughout the experiment. We find that, when correcting for draining vein effects and using both model-based and model-free approaches, the effect of monocular stimulation is largest at deep and middle cortical depths. Conversely, spatial attention influences BOLD activity exclusively near the pial surface. Our findings show that simultaneous interrogation of columnar and laminar dimensions of the cortical fold can dissociate thalamocortical inputs from top-down processing, and allow the investigation of their interactions without any stimulus manipulation.

In Long Evans rats, ocular dominance columns (ODCs) in V1 overlap with patches of callosal connections. Using anatomical tracers, we found that ODCs and callosal patches are present at postnatal day 10 (P10), several days before eye opening, and about 10 days before the activation of the critical period for ocular dominance plasticity (~P20). In rats monocularly enucleated at P10 and perfused ~P20, ODCs ipsilateral to the remaining eye desegregated, indicating that rat ODCs are highly susceptible to monocular enucleation during a precritical period. Monocular enucleation during the critical period exerted significant, although smaller, effects. Monocular eye lid suture during the critical period led to a significant expansion of the ipsilateral projection from the non-deprived eye, whereas the contralateral projection invaded into, and intermixed with, ipsilateral ODCs innervated by the deprived eye. We propose that this intermixing allows callosal connections to contribute to the effects of monocular deprivation assessed in the hemisphere ipsilateral to the non deprived eye. The ipsilateral and contralateral projections from the deprived eye did not undergo significant shrinkage. In contrast, we found that callosal patches are less susceptible to imbalance of eye input. In rats monocularly enucleated during either the precritical or critical periods, callosal patches were maintained in the hemisphere ipsilateral to the remaining eye, but desegregated in the hemisphere ipsilateral to the enucleated orbit. Callosal patches were maintained in rats binocularly enucleated at P10 or later. Similarly, monocular deprivation during the critical period had no significant effect on callosal patches in either hemisphere.

During the early development of the visual cortex, there is a critical period when neuronal connections are highly sensitive to changes in visual input. Deprivation of visual stimuli during the critical period elicits robust anatomical and physiological rearrangements in the monkey visual cortex and serves as an excellent model for activity-dependent neuroplasticity. DNA microarray experiments were previously performed in our lab to analyze gene expression patterns in area V1 of vervet monkeys subjected to monocular deprivation (MD). An interesting candidate identified in its screen was myocyte enhancer-binding factor 2C (MEF2C), a transcription factor linked to neuronal survival. Consistent with the microarray data, we show that there is a qualitative increase in MEF2C protein expression in area V1 of infant as compared to adult vervet monkeys. Our results suggest that the regulation of neuronal survival is one of the molecular mechanisms underlying the critical period for visual cortical neuroplasticity.

Previous anatomical studies of ocular dominance columns (ODCs) in V1 of galagos did not investigate the overall tangential arrangement of eye-specific input in different cortical layers of V1. Likewise, studies using optical imaging of intrinsic signals have not provided information on the pattern of ODCs in layer 4 and deeper layers because this technique detects mostly activity patterns of neurons in the superficial layers. Here we demonstrate the patterns of ODCs across the cortical layers following intraocular injections of the transneuronal tracer WGA-HRP, and correlate these patterns with the array of CO blobs in tangential sections of the flattened cortex. In sections through supragranular V1, the WGA-HRP labeling appears as an array of distinct patches that most likely represent the patchy koniocellular input to layer 3 shown by previous studies. In layer 4, WGA-HRP labeling forms interconnected bands whose overall arrangement resembles the pattern of ODCs in cats. Comparison of the HRP and CO labeling patterns revealed that in supragranular layers, virtually all CO blobs overlap with WGA-HRP labeled patches. Since only one eye was injected with WGA-HRP, these data suggest that CO blobs receive input from both eyes. Moreover, in layer 4, CO blobs are not necessarily centered on ODCs, but often span the borders between left and right columns. Our results provide new information on the distribution and correlation of eye specific input across cortical layers in galago V1, and support the view that the alignment between ODCs and CO blobs seen in macaques is not a general feature of primate V1.

Ocular dominance columns correlate with patchy callosal connections in Long Evans rats (Laing et al., 2015). We explored in vivo manganese-enhanced magnetic resonance imaging (MEMRI) as a possible strategy for longitudinal studies of plastic changes in the retino-thalamo-cortical and callosal pathways. MnCl 2 was injected either intraocularly or intracortically to label these pathways, respectively. The transport of the paramagnetic ion Mn 2+ was evaluated by comparing images acquired both before and 36 or 12 hours after intraocular or cortical injections, respectively. Images were acquired on a 3T magnet (Philips Achieva, Philips Healthcare, Andover, MA), using a custom surface coil and a T1-weighted MPRAGE image sequence (TR/TE = 23/11 ms; Ti=1000 ms; FA= 10 deg acquired matrix 432x432 mm over 118 slices, voxel size 0.11x0.11x0.2 mm 3). To validate the transport of Mn 2+, each animal also received either an intraocular injection of the transneuronal tracer WGA-HRP, or cortical injections of HRP. Following monocular injections of MnCl 2, MRI images showed significant, bilateral accumulations of Mn 2+ in regions of the SC, LGN and visual cortex that corresponded with regions labeled with HRP. In adult rats monocularly enucleated at birth, we injected MnCl 2 in the hemisphere contralateral to the remaining eye in an attempt to detect anomalies reported previously in the callosal pattern ipsilateral to the remaining eye. After the scans, the hemisphere injected with MnCl 2was injected with HRP. MRI images revealed Mn 2+ patterns that closely resembled the callosal patterns demonstrated with HRP in the same animal. Our results suggest that both transneuronal retino-thalamo-cortical, as well as cortico-cortical transport of Mn 2+ provide potentially useful strategies for longitudinal studies of plastic changes in these pathways.

The primary visual cortex of humans contains patches of neurons responding preferentially to stimulation of one eye (the ocular dominance columns). Multiple previous studies attempted to detect their activity using fMRI. The majority of these fMRI studies used magnetic field strengths of 4 ​T and higher. However, there have been reports of reliable eye-selective activations at 3 ​T as well. In this study we investigated the possibility of detecting eye-selective V1 activity using high-resolution GE-EPI fMRI at 3 ​T and sub-millimeter resolution fMRI at ultrahigh 9.4 ​T magnetic field strengths with acquisition parameters optimized for each field strength. High-resolution fMRI at 9.4 ​T also allowed us to examine the eye-selectivity responses across the cortical depth, which are expected to be strongest in the middle layers. We observed a substantial increase in the percentage of eye-selective voxels, as well as a doubling in run-to-run consistency of eye preference at ultrahigh field compared to 3 ​T. We also found that across cortical depth, eye selectivity increased towards the superficial layers, and that signal contrast increased while noise remained nearly constant towards the surface. The depth-resolved results are consistent with a distortion of spatial specificity of the GE-EPI signal by ascending venules and large draining veins on the cortical surface. The effects of larger vessels cause increasing signal amplitude, but also displacement of the maximum BOLD signal relative to neural activity. In summary, our results show that increase in spatial resolution, reduced partial volume effects, and improved sensitivity at 9.4 ​T allow for better detection of eye-selective signals related to ocular dominance columns. However, although ultrahigh field yields higher sensitivity to the ocular dominance signal, GE-EPI still suffers from specificity issues, with a prominent signal contribution at shallow depths from larger cortical vessels.

Ultra-high field MRI can functionally image the cerebral cortex of human subjects at the submillimeter scale of cortical columns and laminae. Here, we investigate both in concert, by, for the first time, imaging ocular dominance columns (ODCs) in primary visual cortex (V1) across different cortical depths. We ensured that putative ODC patterns in V1 (a) are stable across runs, sessions, and scanners located in different continents (b) have a width (∼1.3 mm) expected from post-mortem and animal work and (c) are absent at the retinotopic location of the blind spot. We then dissociated the effects of bottom-up thalamo-cortical input and attentional feedback processes on activity in V1 across cortical depth. Importantly, the separation of bottom-up information flows into ODCs allowed us to validly compare attentional conditions while keeping the stimulus identical throughout the experiment. We find that, when correcting for draining vein effects and using both model-based and model-free approaches, the effect of monocular stimulation is largest at deep and middle cortical depths. Conversely, spatial attention influences BOLD activity exclusively near the pial surface. Our findings show that simultaneous interrogation of columnar and laminar dimensions of the cortical fold can dissociate thalamocortical inputs from top-down processing, and allow the investigation of their interactions without any stimulus manipulation.Significance StatementThe advent of ultra-high field fMRI allows for the study of the human brain non-invasively at submillimeter resolution, bringing the scale of cortical columns and laminae into focus. De Hollander et al imaged the ocular dominance columns and laminae of V1 in concert, while manipulating top-down attention. This allowed them to separate feedforward from feedback processes in the brain itself, without resorting to the manipulation of incoming information. Their results show how feedforward and feedback processes interact in the primary visual cortex, highlighting the different computational roles separate laminae play.