Improved detection following Neuro-Eye Therapy in patients with post-geniculate brain damage

Damage to the optic radiation or the occipital cortex results in loss of vision in the contralateral visual field, termed partial cortical blindness or hemianopia. Previously, we have demonstrated that stimulation in the field defect using visual stimuli with optimal properties for blindsight detection can lead to increases in visual sensitivity within the blind field of a group of patients. The present study was aimed to extend the previous work by investigating the effect of positive feedback on recovery of visual sensitivity. Patients’ abilities for detection of a range of spatial frequencies within their field defect were determined using a temporal two-alternative forced-choice technique, before and after a period of visual training (n = 4). Patients underwent Neuro-Eye Therapy which involved detection of temporally modulated spatial grating patches at specific retinal locations within their field defect. Three patients showed improved detection ability following visual training. Based on our previous studies, we had hypothesised that should the occipital brain lesion extend anteriorly to the thalamus, little recovery would be expected. Here, we describe one such case who showed no improvements after extensive training. The present study provides further evidence that recovery (a) can be gradual and may require a large number of training sessions (b) can be accelerated using positive feedback and (c) may be less likely to take place if the occipital damage extends anteriorly to the thalamus.     

Simultaneous constraints on pre- and post-synaptic cells couple cortical feature maps in a 2D geometric model of orientation preference.

The most prominent feature of mammalian striate cortex (V1) is the spatial organization of response preferences for the position and orientation of elementary visual stimuli. Models for the formation of cortical maps of orientation and 'retinotopic' position typically rely on a combination of Hebbian or correlation-based synaptic plasticity, and constraints on the distribution of synaptic weights. We consider a simplified model of orientation and retinotopic specificity based on the geometry of the feed-forward synaptic weight distribution from an 'unoriented' layer of cells to a first weakly oriented layer. We model the feed-forward weight distribution as a system of planar Gaussian receptive fields each elongated in the direction matching the preferred orientation of the postsynaptic cell. Under the constraint of presynaptic weight normalization (each cell in the oriented layer receives the same net synaptic weight) and a uniform retinotopic map (displacement of centres of mass of receptive fields in the unoriented layer is strictly proportional to the displacement of the corresponding cells in the oriented layer), we find that imposing a pattern of orientation preference forces the system to violate postsynaptic weight normalization (each cell in the unoriented layer no longer sends forth the same net synaptic weight). We study this deviation from uniformity of the postsynaptic weight, and find that the deviation has a distinct form in the vicinity of the 'pinwheel' singularities of the orientation map. We show that uniform synaptic coverage of the unoriented layer can be restored by introducing a distortion in the retinotopic locations of the receptive fields. We calculate, to first order in the relative elongation of the receptive fields, the retinotopic distortion vector field. Both the pattern of postsynaptic weight non-uniformity and the corrective retinotopic distortion vector field fail to possess the reflection symmetry commonly assumed to relate orientation singularities with topological index +/- pi. Hence, we show that 'right-handed' and 'left-handed' orientation singularities are funda-mentally distinct anatomical structures when full 2D synaptic architecture is taken into account. Finally, we predict specific patterns of retinotopic distortion that should obtain in the vicinity of +/- pi-fold orientation singularities, if uniform pre- and post-synaptic weight constraints are strongly enforced.     

Topographic maps of visual spatial attention in human parietal cortex

Functional magnetic resonance imaging (fMRI) was used to measure activity in human parietal cortex during performance of a visual detection task in which the focus of attention systematically traversed the visual field. Critically, the stimuli were identical on all trials (except for slight contrast changes in a fully randomized selection of the target locations) whereas only the cued location varied. Traveling waves of activity were observed in posterior parietal cortex consistent with shifts in covert attention in the absence of eye movements. The temporal phase of the fMRI signal in each voxel indicated the corresponding visual field location. Visualization of the distribution of temporal phases on a flattened representation of parietal cortex revealed at least two distinct topographically organized cortical areas within the intraparietal sulcus (IPS), each representing the contralateral visual field. Two cortical areas were proposed based on this topographic organization, which we refer to as IPS1 and IPS2 to indicate their locations within the IPS. This nomenclature is neutral with respect to possible homologies with well-established cortical areas in the monkey brain. The two proposed cortical areas exhibited relatively little response to passive visual stimulation in comparison with early visual areas. These results provide evidence for multiple topographic maps in human parietal cortex.     

Quantification of Adverse Events Associated with Functional MRI Scanning and with Real-Time fMRI-Based Training

Background

Although functional magnetic resonance imaging (fMRI) is in widespread research use, the safety of this approach has not been extensively quantitatively evaluated. Real-time fMRI (rtfMRI)-based training paradigms use fMRI neurofeedback and cognitive strategies to alter regional brain activation, and are currently being evaluated as a novel approach to treat neurological and psychiatric conditions.

Purpose

The purpose of this study is to determine the incidence and severity of any adverse events that might be caused by changes in brain activation brought about through fMRI or through rtfMRI-based training paradigms.

Method

Quantitative adverse event self-report data were obtained from 641 functional imaging scans in 114 chronic pain patients participating in a research clinical trial examining repeated fMRI scans and rtfMRI-based training. Participants recorded potential adverse events during non-scanning baseline, fMRI scanning, or rtfMRI-based training sessions.

Results

There were no significant increases in the number of reported adverse events following fMRI or rtfMRI scanning sessions compared to baseline non-scanning sessions in a chronic pain trial (N?=?88). There were no reported adverse events of any kind for over 90% of sessions during the course of rtfMRI-based training. When adverse events were reported, they were almost exclusively mild or moderate in severity and similar to those observed in a non-scanning baseline session. There was no increase in adverse events reported by participants receiving feedback from any of four brain regions during repeated rtfMRI-based training scans compared to non-scanning baseline sessions. For chronic pain patients completing the rtfMRI-based training paradigm including up to a total of nine scan sessions (N?=?69), neither the number nor severity of reported events increased during the fMRI or rtfMRI scanning portions of the paradigm. There were no significant increases in the number of reported adverse events in participants who withdrew from the study.

Conclusion

Repeated fMRI scanning and rtfMRI training, consisting of repeated fMRI scanning in conjunction with cognitive strategies and real-time feedback from several regions of interest in multiple brain systems to control brain region activation, were not associated with an increase in adverse event number or severity. These results demonstrate the safety of repetitive fMRI scanning paradigms similar to those in use in many laboratories worldwide, as well as the safety rtfMRI-based training paradigms.     

Functional magnetic resonance imaging mirrors recovery of visual perception after repetitive tachistoscopic stimulation in patients with partial cortical blindness

We investigated three patients with partial cortical blindness after brain injury by means of functional magnetic resonance imaging (fMRI) before and after the application of a daily visual stimulation-therapy over a period of 6 months. Before therapy, fMRI data showed a severely reduced blood-oxygen-level-dependent (BOLD) signal in primary visual cortex when compared to healthy volunteers. Following several months of rehabilitative therapy a neuropsychological improvement of visual functions was accompanied by an increase in BOLD signal of residual perilesional regions whereas fMRI data of the control group remained unchanged. A high capacity of functional recovery and synaptic plasticity of surviving perilesional neuronal structures of primary visual cortex followed by an increased input into post-connected visual areas can be discussed as a basis for the reoccurrence of visual functions.     

Relating retinotopic and object-selective responses in human lateral occipital cortex

What is the relationship between retinotopy and object selectivity in human lateral occipital (LO) cortex? We used functional magnetic resonance imaging (fMRI) to examine sensitivity to retinal position and category in LO, an object-selective region positioned posterior to MT along the lateral cortical surface. Six subjects participated in phase-encoded retinotopic mapping experiments as well as block-design experiments in which objects from six different categories were presented at six distinct positions in the visual field. We found substantial position modulation in LO using standard nonobject retinotopic mapping stimuli; this modulation extended beyond the boundaries of visual field maps LO-1 and LO-2. Further, LO showed a pronounced lower visual field bias: more LO voxels represented the lower contralateral visual field, and the mean LO response was higher to objects presented below fixation than above fixation. However, eccentricity effects produced by retinotopic mapping stimuli and objects differed. Whereas LO voxels preferred a range of eccentricities lying mostly outside the fovea in the retinotopic mapping experiment, LO responses were strongest to foveally presented objects. Finally, we found a stronger effect of position than category on both the mean LO response, as well as the distributed response across voxels. Overall these results demonstrate that retinal position exhibits strong effects on neural response in LO and indicates that these position effects may be explained by retinotopic organization.     

A new psychophysical estimation of the receptive field size

When a line extends beyond the width of an aperture, its direction of motion cannot be detected correctly. Only the component of motion perpendicular to the line is detectable (aperture problem). Early visual areas face the same aperture problem because receptive field sizes are relatively small. The susceptibility of early visual areas to the aperture problem opens an opportunity to measure the aperture width of a receptive field psychophysically that can be used to estimate the receptive field size. We found an already established visual illusion (the rotating tilted lines illusion or RTLI) can be used to measure the aperture size and hence estimate the receptive field size. To estimate the receptive field size, we conducted a psychophysical experiment in which the radii and tilted line length of RTLI were systematically changed. Our psychophysical estimation of receptive field size strongly corresponds with the previous measures of receptive field size using electrophysiological and fMRI methods.     

Spatially specific FMRI repetition effects in human visual cortex

The functional MRI (fMRI) response to a pair of identical, successively presented stimuli can result in a smaller signal than the presentation of two nonidentical stimuli. This "repetition effect" has become a frequently used tool to make inferences about neural selectivity in specific cortical areas. However, little is known about the mechanism(s) underlying the effect. In particular, despite many successful applications of the technique in higher visual areas, repetition effects in lower visual areas [e.g., primary visual cortex (V1)] have been more difficult to characterize. One property that is well understood in early visual areas is the mapping of visual field locations to specific areas of the cortex (i.e., retinotopy). We used the retinotopic organization of V1 to activate progressively different populations of neurons in a rapid fMRI experimental design. We observed a repetition effect (reduced signal) when localized stimulus elements were repeated in identical locations. We show that this effect is spatially tuned and largely independent of both interstimulus interval (100-800 ms) and the focus of attention. Using the same timing parameters for which we observed a large effect of spatial position, we also examined the response to orientation changes and observed no effect of an orientation change on the response to repeated stimuli in V1 but significant effects in other retinotopic areas. Given these results, we discuss the possible causes of these repetition effects as well as the implications for interpreting other experiments that use this potentially powerful imaging technique.     

Metamers of the ventral stream

The human capacity to recognize complex visual patterns emerges in a sequence of brain areas known as the ventral stream, beginning with primary visual cortex (V1). We developed a population model for mid-ventral processing, in which nonlinear combinations of V1 responses are averaged in receptive fields that grow with eccentricity. To test the model, we generated novel forms of visual metamers, stimuli that differ physically but look the same. We developed a behavioral protocol that uses metameric stimuli to estimate the receptive field sizes in which the model features are represented. Because receptive field sizes change along the ventral stream, our behavioral results can identify the visual area corresponding to the representation. Measurements in human observers implicate visual area V2, providing a new functional account of neurons in this area. The model also explains deficits of peripheral vision known as crowding, and provides a quantitative framework for assessing the capabilities and limitations of everyday vision.     

Retinotopic maps and foveal suppression in the visual cortex of amblyopic adults

Amblyopia is a developmental visual disorder associated with loss of monocular acuity and sensitivity as well as profound alterations in binocular integration. Abnormal connections in visual cortex are known to underlie this loss, but the extent to which these abnormalities are regionally or retinotopically specific has not been fully determined. This functional magnetic resonance imaging (fMRI) study compared the retinotopic maps in visual cortex produced by each individual eye in 19 adults (7 esotropic strabismics, 6 anisometropes and 6 controls). In our standard viewing condition, the non-tested eye viewed a dichoptic homogeneous mid-level grey stimulus, thereby permitting some degree of binocular interaction. Regions-of-interest analysis was performed for extrafoveal V1, extrafoveal V2 and the foveal representation at the occipital pole. In general, the blood oxygenation level-dependent (BOLD) signal was reduced for the amblyopic eye. At the occipital pole, population receptive fields were shifted to represent more parafoveal locations for the amblyopic eye, compared with the fellow eye, in some subjects. Interestingly, occluding the fellow eye caused an expanded foveal representation for the amblyopic eye in one early–onset strabismic subject with binocular suppression, indicating real-time cortical remapping. In addition, a few subjects actually showed increased activity in parietal and temporal cortex when viewing with the amblyopic eye. We conclude that, even in a heterogeneous population, abnormal early visual experience commonly leads to regionally specific cortical adaptations.     

High-resolution two-dimensional spatial mapping of cat striate cortex using a 100-microelectrode array

Much of our understanding of the visuotopic organization of striate cortex results from single-electrode penetrations and serial recording of receptive field properties. However, the quality of these maps is limited by imprecision in quantifying electrode position, combining data from multiple laminae, and eye drift during the measurement of the receptive field properties. We have addressed these concerns by using an array of 100 closely spaced microelectrodes to investigate the two-dimensional visuotopic organization of layer IV in cat striate cortex. This array allowed simultaneous measurement of the receptive field properties of multiple single units on a regularly spaced grid. We found the relationship between cortical and visual space to be locally non-conformal: the receptive field locations associated with a closely spaced line of electrodes appeared randomly scattered in visual space. To quantify the scatter, we fitted a linear transformation of electrode sites onto the associated receptive field locations. We found that the distribution of the difference between the predicted receptive field location and the measured location had standard deviations of 0.59 degrees and 0.45 degrees in the horizontal and the vertical axes, respectively. Although individual receptive field positions differed from the predicted locations in a non-conformal sense, the trend across multiple receptive fields followed the maps described elsewhere. We found, on average, that the 13 mm2 of cortex sampled by the array mapped onto a 5.8-degrees) region of visual space. From the scaling of this map and a combination of the statistics of the receptive field size (2.7+/-1.5 degrees) and scatter, we have explored the impact of electrode spacing on the completeness and redundancy in coverage of visual space sampled by an array. The simulation indicated an array with 1.2-mm spacing would completely sample the region of visual space addressed by the array. These results have implications for neuroprosthetic applications. Assuming phosphene organization resembles the visuotopic organization, remapping of visual space may be necessary to accommodate the scatter in phosphene locations.     

Predictive coding for motion stimuli in human early visual cortex

The current study investigates if early visual cortical areas, V1, V2 and V3, use predictive coding to process motion information. Previous studies have reported biased visual motion responses at locations where novel visual information was presented (i.e., the motion trailing edge), which is plausibly linked to the predictability of visual input. Using high-field functional magnetic resonance imaging (fMRI), we measured brain activation during predictable versus unpreceded motion-induced contrast changes during several motion stimuli. We found that unpreceded moving dots appearing at the trailing edge gave rise to enhanced BOLD responses, whereas predictable moving dots at the leading edge resulted in suppressed BOLD responses. Furthermore, we excluded biases in directional sensitivity, shifts in cortical stimulus representation, visuo-spatial attention and classical receptive field effects as viable alternative explanations. The results clearly indicate the presence of predictive coding mechanisms in early visual cortex for visual motion processing, underlying the construction of stable percepts out of highly dynamic visual input.     

Spatio-temporal plasticity of cortical receptive fields in response to repetitive visual stimulation in the adult cat

Many psychophysical experiments on perceptual learning in humans show increases of performance that are most probably based on functions of early visual cortical areas. Long-term plasticity of the primary visual cortex has so far been shown in vivo with the use of visual stimuli paired with electrical or pharmacological stimulation at the cellular level. Here, we report that plasticity in the adult visual cortex can be achieved by repetitive visual stimulation. First, spatial receptive field profiles of single units (n=38) in area 17 or 18 of the anesthetized cat were determined with optimally oriented flashing light bars. Then a conditioning protocol was applied to induce associative synaptic plasticity. The receptive field center and an unresponsive region just outside the excitatory receptive field were synchronously stimulated ('costimulation', repetition rate 1 Hz; for 10-75 min). After costimulation the receptive field and its adjacent regions were mapped again. We observed specific increases of the receptive field size, changes of the receptive field subfield structure as well as shifts in response latency.In 37% of the cells the receptive field size increased specifically towards the stimulated side but not towards the non-stimulated opposite side of the receptive field. In addition, changes in the relative strength and size of the on and off subfield regions were observed. These specific alterations were dependent on the level of neuronal activity during costimulation. During recovery, the new responses dropped down to 120% of the preconditioning value on average within 103 min; however, the decay times significantly depended on the response magnitude after costimulation. In the temporal domain, the latency of new responses appeared to be strongly influenced by the latency of the response during costimulation.Twenty-nine percent of the units displayed no receptive field enlargement, most likely because the activity during costimulation was significantly lower than in the cases with enlarged receptive fields. An unspecific receptive field enlargement towards both the stimulated and non-stimulated side was observed in 34% of the tested cells. In contrast to the cells with specifically enlarged receptive fields, the unspecific increase of receptive field size was always accompanied by a strong increase of the general activity level.We conclude that the receptive field changes presumably took place by strengthening of synaptic inputs at the recorded cells in a Hebbian way as previously shown in the visual cortex in vitro and in vivo. The observed receptive field changes may be related to preattentive perceptual learning and could represent a basis of the 'filling in' of cortical scotomas obtained with specific training procedures in human patients suffering from visual cortex lesions.     

Visual responses of the human superior colliculus: a high-resolution functional magnetic resonance imaging study

The superior colliculus (SC) is a multimodal laminar structure located on the roof of the brain stem. The SC is a key structure in a distributed network of areas that mediate saccadic eye movements and shifts of attention across the visual field and has been extensively studied in nonhuman primates. In humans, it has proven difficult to study the SC with functional MRI (fMRI) because of its small size, deep location, and proximity to pulsating vascular structures. Here, we performed a series of high-resolution fMRI studies at 3 T to investigate basic visual response properties of the SC. The retinotopic organization of the SC was determined using the traveling wave method with flickering checkerboard stimuli presented at different polar angles and eccentricities. SC activations were confined to stimulation of the contralateral hemifield. Although a detailed retinotopic map was not observed, across subjects, the upper and lower visual fields were represented medially and laterally, respectively. Responses were dominantly evoked by stimuli presented along the horizontal meridian of the visual field. We also measured the sensitivity of the SC to luminance contrast, which has not been previously reported in primates. SC responses were nearly saturated by low contrast stimuli and showed only small response modulation with higher contrast stimuli, indicating high sensitivity to stimulus contrast. Responsiveness to stimulus motion in the SC was shown by robust activations evoked by moving versus static dot stimuli that could not be attributed to eye movements. The responses to contrast and motion stimuli were compared with those in the human lateral geniculate nucleus. Our results provide first insights into basic visual responses of the human SC and show the feasibility of studying subcortical structures using high-resolution fMRI.     

Influence of electrotonic structure and synaptic mapping on the receptive field properties of a collision-detecting neuron

The lobula giant movement detector (LGMD) is a visual interneuron of Orthopteran insects involved in collision avoidance and escape behavior. The LGMD possesses a large dendritic field thought to receive excitatory, retinotopic projections from the entire compound eye. We investigated whether the LGMD's receptive field for local motion stimuli can be explained by its electrotonic structure and the eye's anisotropic sampling of visual space. Five locust (Schistocerca americana) LGMD neurons were stained and reconstructed. We show that the excitatory dendritic field and eye can be fitted by ellipsoids having similar geometries. A passive compartmental model fit to electrophysiological data was used to demonstrate that the LGMD is not electrotonically compact. We derived a spike rate to membrane potential transform using intracellular recordings under visual stimulation, allowing direct comparison between experimental and simulated receptive field properties. By assuming a retinotopic mapping giving equal weight to each ommatidium and equally spaced synapses, the model reproduced the experimental data along the eye equator, though it failed to reproduce the receptive field along the ventral-dorsal axis. Our results illustrate how interactions between the distribution of synaptic inputs and the electrotonic properties of neurons contribute to shaping their receptive fields.     

The representation of perceived angular size in human primary visual cortex

Two objects that project the same visual angle on the retina can appear to occupy very different proportions of the visual field if they are perceived to be at different distances. What happens to the retinotopic map in primary visual cortex (V1) during the perception of these size illusions? Here we show, using functional magnetic resonance imaging (fMRI), that the retinotopic representation of an object changes in accordance with its perceived angular size. A distant object that appears to occupy a larger portion of the visual field activates a larger area in V1 than an object of equal angular size that is perceived to be closer and smaller. These results demonstrate that the retinal size of an object and the depth information in a scene are combined early in the human visual system.     

3D shape perception from combined depth cues in human visual cortex

Our perception of the world's three-dimensional (3D) structure is critical for object recognition, navigation and planning actions. To accomplish this, the brain combines different types of visual information about depth structure, but at present, the neural architecture mediating this combination remains largely unknown. Here, we report neuroimaging correlates of human 3D shape perception from the combination of two depth cues. We measured fMRI responses while observers judged the 3D structure of two sequentially presented images of slanted planes defined by binocular disparity and perspective. We compared the behavioral and fMRI responses evoked by changes in one or both of the depth cues. fMRI responses in extrastriate areas (hMT+/V5 and lateral occipital complex), rather than responses in early retinotopic areas, reflected differences in perceived 3D shape, suggesting 'combined-cue' representations in higher visual areas. These findings provide insight into the neural circuits engaged when the human brain combines different information sources for unified 3D visual perception.     

NMDA antagonists in the superior colliculus prevent developmental plasticity but not visual transmission or map compression

Partial ablation of the superior colliculus (SC) at birth in hamsters compresses the retinocollicular map, increasing the amount of visual field represented at each SC location. Receptive field sizes of single SC neurons are maintained, however, preserving receptive field properties in the prelesion condition. The mechanism that allows single SC neurons to restrict the number of convergent retinal inputs and thus compensate for induced brain damage is unknown. In this study, we examined the role of N-methyl-D-aspartate (NMDA) receptors in controlling retinocollicular convergence. We found that chronic 2-amino-5-phosphonovaleric acid (APV) blockade of NMDA receptors from birth in normal hamsters resulted in enlarged single-unit receptive fields in SC neurons from normal maps and further enlargement in lesioned animals with compressed maps. The effect was linearly related to lesion size. These results suggest that NMDA receptors are necessary to control afferent/target convergence in the normal SC and to compensate for excess retinal afferents in lesioned animals. Despite the alteration in receptive field size in the APV-treated animals, a complete visual map was present in both normal and lesioned hamsters. Visual responsiveness in the treated SC was normal; thus the loss of compensatory plasticity was not due to reduced visual responsiveness. Our results argue that NMDA receptors are essential for map refinement, construction of receptive fields, and compensation for damage but not overall map compression. The results are consistent with a role for the NMDA receptor as a coincidence detector with a threshold, providing visual neurons with the ability to calculate the amount of visual space represented by competing retinal inputs through the absolute amount of coincidence in their firing patterns. This mechanism of population matching is likely to be of general importance during nervous system development.     

Predictive remapping of attention across eye movements

Many cells in retinotopic brain areas increase their activity when saccades (rapid eye movements) are about to bring stimuli into their receptive fields. Although previous work has attempted to look at the functional correlates of such predictive remapping, no study has explicitly tested for better attentional performance at the future retinal locations of attended targets. We found that, briefly before the eyes start moving, attention drawn to the targets of upcoming saccades also shifted to those retinal locations that the targets would cover once the eyes had moved, facilitating future movements. This suggests that presaccadic visual attention shifts serve to both improve presaccadic perceptual processing at the target locations and speed subsequent eye movements to their new postsaccadic locations. Predictive remapping of attention provides a sparse, efficient mechanism for keeping track of relevant parts of the scene when frequent rapid eye movements provoke retinal smear and temporal masking.