Primary Visual Cortex

The whole brain was divided into 24 regions by NeuroQ software. Our data found that the mean uptake ratios of the caudate nucleus and lentiform nucleus were higher in patients with FOG than those without FOG by variance analysis (p<0.05). After adjusting for age and sex by covar- iance, the mean uptake ratios of the caudate nucleus and lentiform nucleus were still higher in the FOG group com- pared with those without FOG (p<0.05). The mean uptake ratio of the left primary visual cortex was signi fi cantly lower in the FOG group than that in the non-FOG group after adjusting for age and sex by covariance analysis (p<0.05). There were no differences of uptake ratios detected by

Fig 2. Synchronized BOLD fluctuations. A, Time series data from 1 subject. Six minutes of data are shown. Traces represent average BOLD signal intensity from regions of interest in the bilateral primary visual cortex (V1), left LGN, and bilateral frontal eye fields (FEF). B, Cross-correlation analysis represents full 14-minute resting state data from regions listed previously. Bilateral V1 shows strong focal correlation, with similar but diminished correlation between V1 and LGN. No correlation is seen between V1 and FEF. Bilateral FEF show much broader temporal correlation. C, Summary resting state BOLD cross-correlation from 6 subjects. Green traces show cross-correlograms for individual subjects, and black traces show an average cross-correlogram across subjects (bilateral V1, n ⫽ 6; left V1-left LGN, n ⫽ 3; left V1-left FEF, n ⫽ 2, left FEF-right FEF: n ⫽ 2).

Aging often results in reduced visual acuity from changes in both the eye and neural circuits [1-4]. In normally aging subjects, primary visual cortex has been shown to have reduced responses to visual stimulation [5]. It is not known, however, to what extent aging affects visual field repre- sentations and population receptive sizes in human primary visual cortex. Here we use func- tional MRI (fMRI) and population receptive field (pRF) modeling [6] to measure angular and ec- centric retinotopic representations and popula- tion receptive fields in primary visual cortex in healthy aging subjects ages 57 - 70 and in healthy young volunteers ages 24 - 36 (n = 9). Retinotopic stimuli consisted of black and white, drifting checkerboards comprising moving bars 11 deg in radius. Primary visual cortex (V1) was clearly identifiable along the calcarine sulcus in all hemispheres. There was a significant de- crease in the surface area of V1 from 0 to 3 deg eccentricity in the aging subjects with respect to the young subjects (p = 0.039). The coherence of the fMRI% BOLD modulation was significantly decreased in the aging subjects compared to the young subjects in the more peripheral eccen- tricity band from 7 to 10 deg (p = 0.029). Finally, pRF sizes were significantly increased within the 0 to 3 deg foveal representation of V1 in the aging subjects compared to the young subjects (p = 0.019). Understanding the extent of changes that occur in primary visual cortex during nor- mal aging is essential both for understanding the normal aging process and for comparisons of healthy, aging subjects with aging patients suffering from age-related visual and cortical disorders.

The largest visual area, known as the primary visual cortex or V1, has greatly contributed to the current understanding of mam- malian and human visual pathways and their role in visual perception. The initial discovery of orientation-sensitive neurons in V1, arranged according to a retinotopic mapping, suggested an analogy to its function as a low-level feature analyser. Subsequent discoveries of phase, spatial frequency, color, ocular origin, and direction-of-motion-sensitive neurons, arranged into overlapping maps, further lent support to the view that it performs a rich decomposition, similar to signal processing transforms, of the retinal output. Like the other cortical areas, V1 has a laminar organization with specialization for input from the relayed retinal afferents, output to the higher visual areas, and the segregation of the magno (motion) and parvo (form) pathways. Spatially lateral con- nections that exist between neurons of similar and varying properties have also been proposed to give rise to a computation of a bottom-up saliency map in V1. We provide a review of the selectivity of neurons in V1, laminar specialization and analogies to signal processing techniques, a model of V1 saliency computation, and higher-area feedback that may mediate perception. Copyright © 2007 Jeffrey Ng et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract—It is traditional to believe that neurons in primary visual cortex are sensitive only or principally to stimulation within a spatially restricted receptive field (classical receptive field). It follows from this that they should only be capable of encoding the direction of stimulus movement orthogonal to the local contour, since this is the only information available in their classical receptive field “aperture.” This direction is not necessarily the same as the motion of the entire object, as the direction cue within an aperture is ambiguous to the global direction of motion, which can only be derived by integrating with unambiguous components of the object. Re- cent results, however, show that primary visual cortex neu- rons can integrate spatially and temporally distributed cues outside the classical receptive field, and so we reexamined whether primary visual cortex neurons suffer the “aperture problem.” With the stimulation of an optimally oriented bar drifting across the classical receptive field in different global directions, here we show that a subpopulation of primary visual cortex neurons (25/81) recorded from anesthetized and paralyzed marmosets is capable of integrating informative unambiguous direction cues presented by the bar ends, well outside their classical receptive fields, to encode global mo- tion direction. Although the stimuli within the classical recep- tive field were identical, their directional responses were sig- nificantly modulated according to the global direction of stimulus movement. Hence, some primary visual cortex neu- rons are not local motion energy filters, but may encode signals that contribute directly to global motion processing. © 2005 Published by Elsevier Ltd on behalf of IBRO. Key words: direction selectivity, aperture problem, motion, primary visual cortex, monkey.

Background: Previous studies demonstrated that early blindness is associated with abnormal intrinsic functional connectivity (FC) between the primary visual cortex (V1) and other sensory areas. However, the V1 pattern of spontaneous neural activity occurring in late blindness (LB) remains unknown. The purpose of this study was to investigate the intrinsic FC patterns of V1 in LB. Materials and methods: Thirty LB individuals (18 males and 12 females; mean age: 38.76±14.43 years) and 30 sighted controls (SCs) individuals (18 males and 12 females; mean age: 38.67±13.85 years) closely matched for age, sex, and education, underwent resting-state magnetic resonance imaging scans. Region of interest analysis was performed to extract the cor- relation coefficient matrix among each pair of Brodmann area (BA) 17 and FC between V1 and vision-related subcortical nuclei.

Interestingly, recent work now suggests that neuronal adaptation may also not produce hard-wired changes over the long-term. Using immersive virtual reality, Haak et al. (2014b) exposed a group of young adults to a world with only very little vertical visual contrast energy for four days continuously, in an attempt to mimic classic selective rearing experiments (Hirsch and Spinelli, 1970; Blakemore and Cooper, 1970) in adult humans. Just as staring at a waterfall for a prolonged period of time changes the response gains of motion-sensitive neurons, the prolonged viewing of a world with relatively little vertical contrast will cause adjustments to the responsiveness of orientation-selective cells in primary visual cortex (e.g., Graham, 1989; Maffei et al., 1973; Movshon and Lennie, 1973; Ohzawa et al., 1985; Dragoi et al., 2000). Monitoring for the perceptual consequences of these changes in the responsiveness of orientation-selective neurons, Haak et al. (2014b) found that adaptation increased in magnitude during the first day, but then decreased, despite the sustained presence of the adapting environment. Thus, it appears that there are factors that prevent visual neuroplasticity, in the form of neuronal adaptation, from being sustained over the long-term.

Our goal was to quantify the modulation of gamma oscillations (20-50 Hz) through the depth of the mouse primary visual cortex (V1) in response to changes in stimulus characteristics. Using full screen drifting sinusoidal gratings, we manipulated stimulus intensity by changing contrast and stimulus specificity by changing orientation. We recorded local field potentials (LFPs) using a multisite probe (Neuronexus, Ann Arbor, MI) with 16 evenly spaced recording sites (50 or 100 µm interelectrode distance) inserted normal to the cortical surface and spanning the cortical depth. We also recorded single cells from layers 2-6 using 5-7 independently movable tetrodes (Thomas Recordings, Giessen, Germany). Mice were anesthetized with a mix of isoflurane and xylazine in order to obtain a stable low amplitude spontaneous baseline pattern recorded in the LFPs. The visual responses described here were readily abolished or became highly variable when the anesthesia level induced slow oscillations in the background activity. We obtained recordings from 21 probes from 18 animals, from which we selected 18 probes from 13 animals for orientation analysis based on the stability and amplitude of visual responses and the absence of slow oscillations in the baseline. Among these, we further selected 5 probes from 4 animals for the analysis of contrast manipulations.

In the self-organization process, the neurons developed oriented receptive fields organized into orientation columns very similar to those observed in the primary visual cortex (figure 3b). The strongest lateral connections of highly-tuned cells link areas of similar orientation preference, and avoid neurons with the orthogonal orientation preference. Furthermore, the connection patterns of highly oriented neurons are typically elongated along the direction in the map that corresponds to the neuron’s preferred stimulus orientation (as subsequently found experimentally by Bosking et al., 1997.) This organization reflects the activity correlations caused by the elongated Gaussian input pattern: such a stimulus activates primarily those neurons that are tuned to the same ori- entation as the stimulus, and located along its length (Sirosh et al., 1996). Since the long-range lateral connections are inhibitory, the net result is decorrelation: redundant activation is removed, resulting in a sparse representation of the novel features of each input (Barlow, 1990; Field, 1994; Sirosh et al., 1996). As a side effect, illusions and aftereffects may sometimes occur, as will be shown below.

The processing of visual information by the nervous system requires significant metabolic resources. To minimize the energy needed, our visual system appears to be optimized to encode typical natural images as efficiently as possible. One consequence of this is that some atypical images will produce inefficient, non- optimal responses. Here, we show that images that are reported to be uncomfortable to view, and that can trigger migraine attacks and epileptic seizures, produce relatively non-sparse responses in a model of the primary visual cortex. In comparison with the responses to typical inputs, responses to aversive images were larger and less sparse. We propose that this difference in the neural population response may be one cause of visual discomfort in the general population, and can produce more extreme responses in clinical populations such as migraine and epilepsy sufferers.

layers and different groups of excitatory cells (and inhibitory cells), and they are likely to serve different functions; some cells are more concerned with receiving visual inputs, whereas other cells process the signals and send outputs to higher visual centers (Salin & Bullier, 1995). It is not yet clear what the target cell types are for the higher center feedback (Salin & Bullier, 1995). Cortical neurons interact with each other locally and often reciprocally; the excitatory connections extend somewhat longer distances than the inhibitory ones (Douglas & Martin, 1990; White, 1989). These neural interactions typically link neurons with similar RF properties (White, 1989). The anatomical basis for the surround effect has been postulated to be the long-range horizontal connections linking cells up to 4 mm or more apart in the primary visual cortex (e.g., Kapadia et al., 1995; Gilbert, 1992; All- man et al., 1985). These connections emanate from the excitatory pyramidal cells in upper layers and contact both the excitatory and inhibitory post- synaptic cells, enabling monosynaptic excitation and disynaptic inhibition from one cortical site to another (Gilbert, 1992; McGuire, Gilbert, Rivlin, & Wiesel, 1991; Hirsch & Gilbert, 1991; Weliky, Kandler, Fitzpatrick, & Katz, 1995). The axonal fields of these connections are asymmetrical, extending for greater distances along one cortical axis than another (Rockland & Lund, 1983; Gilbert & Wiesel, 1983; Fitzpatrick, 1996). Cells preferring similar ori- entations tend to be linked (Ts’o, Gilbert, & Wiesel, 1986; Gilbert & Wiesel, 1989; Malach, Amir, Harel, & Grinvald, 1993) whether or not the relative dis- placements of their receptive field centers are aligned with or orthogonal to their preferred orientations (Gilbert & Wiesel, 1983).

In summary, previous studies into the neural basis of enhanced peripheral visual acuity in congenitally deaf humans have found alterations in auditory cortex, as well as attention related areas in higher visual and parietal cortex. However, studies using retinotopic mapping to contrast the size and activation in early visual areas between deaf and hearing participants have found no group differences. The methods used in previous studies however did not permit a precise assessment of the spatial selectivity of visual cortical voxels. More recent studies of the retina and visual thalamocortical tract in congenitally deaf humans have found alterations in these structures which, given the hierarchichal structure of the visual cortex, suggests closer examination of the cortical architecture in early visual areas is warranted. In the current study we used visual psychophysics and fMRI with population receptive field modeling to measure the structural and functional properties of primary visual cortex. We contrasted hearing and congenitally deaf participants to determine whether plasticity in these regions could account for the enhanced peripheral vision observed in deaf people. We employed visual stimulation of a wide field of view up to an eccentricity of 37.5 degrees to particularly assess differences in the peripheral visual field, as we predicted differences would be concentrated in these regions. Based on previous findings that increased cortical magnification factor [34] (and so decreased population receptive field size [35, 36]) is associated with increased acuity, we predicted that the deaf group would have decreased population receptive field sizes in the visual periphery. White matter alterations in the visual thalamus and visual thalamocortical tract have been reported in congenital deafness [31]; we wanted to determine whether these structural abnormalities persisted into the cortical visual processing hierarchy. Increased cortical thickness in visual areas has been reported in blind participants [37, 38] and linked to reduced visual acuity [39]. As such, we predicted thinner visual cortex in the deaf group.

Recurrent neural dynamics is a basic computational substrate for cortical process- ing. In the primary visual cortex, this recurrent dynamics is instantiated by finite range, lateral, intra-cortical neural connections. The input to the cortex is the reti- nal image filtered through cortical receptive fields (RFs) shaped like small edges or bars and retinotopically distributed in visual space. The outputs of the cortex are the cell activities, which can be viewed as a complex nonlinear transform of the input under the recurrent interactions. Two characteristics of this transform follow immediately. First, if we focus on cases when top-down feedback from higher vi- sual areas does not change during the course of the transform, the primary cortical computation is autonomous, suggesting that the computation concerned is pre- attentive in nature. In other words, we consider cases when feedback from higher visual areas is purely passive and its role is merely to set a background or operat- ing point for V1 computation. This enables us to isolate the recurrent dynamics in V1 for thorough study. Of course, more extensive computations can doubtless be performed when V1 interacts dynamically with other visual areas; however, this

We have previously shown that luminance gratings induce gamma band activity as increases in power within the primary visual cortex (Adjamian et al., 2004). The strength of this activity is dependent upon the spatial frequency (SF) of gratings with maximal activity for gratings of 2–4 cycles per degree (cpd). Moreover, we detected no activity arising from extrastriate visual areas for most SFs, particularly those of 2–4 cpd. This finding indicated that local gamma activity in V1 is highly sensitive to and contingent upon this elementary feature of the visual stimulus. Moreover, spectral analysis of the stimulus-related induced activity for gratings of 3 cpd demonstrated that this activity develops its maximum with stimulus onset, lasting the duration of its presentation, and ceases rapidly after the removal of the stimulus. In a similar study, Hall et al. (2005) have recently shown that gamma activity in the visual cortex has a linear relation- ship with stimulus contrast such that as grating contrast increases so does the induced gamma activity. Moreover, they show that gamma activity in V1 is represented such that the location of the activity depends on the quadrant in which the grating stimulus is displayed, thus conforming to retinotopic organization of early visual areas. We have also shown that in addition to the varying magnitude and spatial extent of induced gamma activity, its temporal

The study was performed on neurons with dire- ction selective (DS) receptive fields (RFs) in the primary visual cortex of the cat. Preferred dire- ctions (PDs) of these cells to a single light spot and a system of two identical light spots moving across the RF with a given angle between them were compared. Directional interactions appear- ed when the angles between the directions of the two moving spots were 30º or 60º. PD for 56% of the cells coincided with bisectors of these ang- les. These cells responded to a combination of the two moving stimuli as if only one stimulus moved in the RF in an intermediate direction. This direction coincided with PD of the DS neu- ron to a single spot. Also, the investigation rev- ealed that DS neurons responded to stimuli moving at such angles as 180º (to preferred and opposite directions simultaneously). In the fur- ther experiment we investigated responses of the DS cells in the primary visual cortex of RF. The angle between the directions of the two mo- ving spots was 60º. These cells responded to a combination of the two moving stimuli as if only one stimulus moved in RF in an intermediate direction. The more relative luminance of one of spots in pair was, the closer the intermediate dir- ection approached to the direction of this spot).

Gain control is a salient feature of information processing throughout the visual system. Heeger (1991, 1992) described a mechanism that could underpin gain control in primary visual cortex (V1). According to this model, a neuron’s response is normalized by dividing its output by the sum of a population of neurons, which are selective for orientations covering a broad range. Gain control in this scheme is manifested as a change in the semisaturation constant (contrast gain) of a V1 neuron. Here we examine how flanking and annular gratings of the same or orthogonal orientation to that preferred by a neuron presented beyond the receptive field modulate gain in V1 neurons in anesthetized marmosets (Callithrix jacchus). To characterize how gain was modulated by surround stimuli, the Michaelis–Menten equation was fitted to response versus contrast functions obtained under each stimulus condition. The modulation of gain by surround stimuli was modelled best as a divisive reduction in response gain. Response gain varied with the orientation of surround stimuli, but was reduced most when the orientation of a large annular grating beyond the classical receptive field matched the preferred orientation of neurons. The strength of surround suppression did not vary significantly with retinal eccentricity or laminar distribution. In the marmoset, as in macaques (Angelucci et al., 2002a,b), gain control over the sort of distances reported here (up to 10 deg) may be mediated by feedback from extrastriate areas.

In our experimental condition, spatial loca- tion of the activated cortex was not in question, in that the location of primary visual cortex has long been known. Further, the stimulus used resulted in diffuse activation of the primary vi- sual cortex. Thus, we were not depending on the spatial distribution of the functional MR signal changes to help in locating regions of cortical activation. Similarly, few if any of the published functional MR studies depend primarily on the functional MR signal changes for precise loca- tion of the activated regions; the spatial distri- bution of the observed signal changes typically are used to confirm functional location that has been previously documented or predicted using other experimental techniques (4, 5, 14, 18, 19, 33). In experimental circumstances under which the distribution of cortical activation is not known, location of cortical activation on the basis of the spatial distribution of gradient echo- based functional MR signal changes may lead to spurious results, in that the paths taken by the small regional veins contributing to the signal changes may not consistently overlie the re- gions of activated tissue. This is relevant be- cause many investigators will not have access to MR instruments with a field strength of greater than 1.5-T, and at this field strength, readily implemented gradient-echo techniques yield signal changes that are much easier to detect than those seen with spin-echo se- quences. A possible solution is the use of a technique such as statistical parametric map-

Normal development of primary visual cortex is shaped by visual experience and mirrored by region-specific ac- tivity reporter gene expression, in conjunction with the previously described central-to-peripheral maturation gradients in the visual system (reviewed in [11]). During normal development, in cat, the peripheral region of area 17 still undergoes intensive developmental changes between the 2 nd and 4 th month of age when its central counterpart is already in a more mature state [8]. We also witnessed such a centro-peripheral maturation gradient in 1N and 2N kittens based on protein expres- sion patterns. As predicted, BD exerted a cortical region-specific effect on these protein expression pro- files. Several of these developmental protein expression changes occurring between 2 and 4 months in normal animals (Table 1; column normal/age; rows 1–20) were absent in BD subjects. In fact, protein expression in peripheral area 17 hardly differed between 4BD kittens and the younger 2N animals, confirming our previous results where we showed that BD exerts a stronger delay effect on the maturation of peripheral area 17 as measured by visually-induced activity reporter gene zif268 expression [8]. Additionally, under BD, centro- peripheral differences were observed up to 4 months. Together, these observations indicate that BD may not only delay but also prolong and enhance the centro- peripheral protein expression gradient related to the development of area 17. In sum, by exploiting the im- pact of BD on cortical maturation we could implicate four biological processes and thirty-six proteins in vis- ual cortex development.

Magnetoencephalography (MEG) can be used to reconstruct neuronal activity with high spatial and temporal resolution. However, this reconstruction problem is ill-posed, and requires the use of prior constraints in order to produce a unique solution. At present there are a multitude of inversion algorithms, each employing different assumptions, but one major problem when comparing the accuracy of these different approaches is that often the true underlying electrical state of the brain is unknown. In this study, we explore one paradigm, retinotopic mapping in the primary visual cortex (V1), for which the ground truth is known to a reasonable degree of accuracy, enabling the comparison of MEG source reconstructions with the true electrical state of the brain. Specifically, we attempted to localize, using a beamforming method, the induced responses in the visual cortex generated by a high contrast, retinotopically varying stimulus. Although well described in primate studies, it has been an open question whether the induced gamma power in humans due to high contrast gratings derives from V1 rather than the prestriate cortex (V2). We show that the beamformer source estimate in the gamma and theta bands does vary in a manner consistent with the known retinotopy of V1. However, these peak locations, although retinotopically organized, did not accurately localize to the cortical surface. We considered possible causes for this discrepancy and suggest that improved MEG ⁄ magnetic resonance imaging co-registration and the use of more accurate source models that take into account the spatial extent and shape of the active cortex may, in future, improve the accuracy of the source reconstructions.

All these observations show that the surround of a classical receptive field influences a cell's response to simulations of natural stimuli. A wide range of surround effects have been isolated, many inhibitory, others facilitatory. These have been found to depend on stimulus parameters such as orientation and spatial frequency. Where surround stimuli facilitate responses to centre stimuli, possible mechanisms might be directly excitatory or dis-inhibitory in nature. Inhibitory effects could be mediated directly by inhibitory interneurons or via surround driven excitatory mechanisms that provide input to local inhibitory circuits. Interactions between different points in visual space indicate that these surround effects might be mediated by the long horizontal projections of excitatory and inhibitory cells in the cortex, or feedback from higher visual areas. Inputs that mediate surround mechanisms appear to be sub­ threshold, since the degree to which surround stimuli can drive a cell in isolation is very limited, they mainly influence a cell's response to more optimal stimuli. Appropriate spatially distributed stimuli can modulate the response of the classical receptive field, thus it is important to consider the classically defined receptive field in the context of visual response specificity that surround it. These observations have the implication that in order to properly describe the stimulus specificity of a cell, in a way that is relevant to human vision, stimuli must be used that contain a contextual component. Classical analysis using bar stimuli, has succeeded in describing the excitatory centre, however such stimuli do not simulate the challenges of the natural environment. Cortical cells at a given point in visual space 'see' features in context, surrounded by other features, they do not see bright bars set in a fields of neutral contrast. In this investigation contextual stimuli were used to stimulate large areas of the visual field, while anatomically distributed cells with spatially distributed fields were recorded simultaneously. In the section below the discussion will focus on how these visual responses are made by interacting networks of cells.