We present a comprehensive review of the rare syndrome visual form agnosia (VFA). We begin by documenting its history, including the origins of the term, and the first case study labelled as VFA. The defining characteristics of the syndrome, as others have previously defined it, are then described. The impairments, preserved aspects of visual perception, and areas of brain damage in 21 patients who meet these defining characteristics are described in detail, including which tests were used to verify the presence or absence of key symptoms. From this, we note important similarities along with notable areas of divergence between patients. Damage to the occipital lobe (20/21), an inability to recognise line drawings (19/21), preserved colour vision (14/21), and visual field defects (16/21) were areas of consistency across most cases. We found it useful to distinguish between shape and form as distinct constructs when examining perceptual abilities in VFA patients. Our observations suggest that these patients often exhibit difficulties in processing simplified versions of form. Deficits in processing orientation and size were uncommon. Motion perception and visual imagery were not widely tested for despite being typically cited as defining features of the syndrome - although in the sample described, motion perception was never found to be a deficit. Moreover, problems with vision (e.g., poor visual acuity and the presence of hemianopias/scotomas in the visual fields) are more common than we would have thought and may also contribute to perceptual impairments in patients with VFA. We conclude that VFA is a perceptual disorder where the visual system has a reduced ability to synthesise lines together for the purposes of making sense of what images represent holistically.

Patients with visual agnosia show severe deficits in recognizing two-dimensional (2-D) images of objects, despite the fact that early visual processes such as figure-ground segmentation, and stereopsis, are largely intact. Strikingly, however, these patients can nevertheless show a preservation in their ability to recognize real-world objects -a phenomenon known as the \'real-object advantage\' (ROA) in agnosia. To uncover the mechanisms that support the ROA, patients were asked to identify objects whose size was congruent or incongruent with typical real-world size, presented in different display formats (real objects, 2-D and 3-D images). While recognition of images was extremely poor, real object recognition was surprisingly preserved, but only when physical size matched real-world size. Analogous display format and size manipulations did not influence the recognition of common geometric shapes that lacked real-world size associations. These neuropsychological data provide evidence for a surprising preservation of size-coding of real-world-sized tangible objects in patients for whom ventral contributions to image processing are severely disrupted. We propose that object size information is largely mediated by dorsal visual cortex and that this information, together with detailed representation of object shape which is also subserved by dorsal cortex, serve as the basis of the ROA.

The two-visual-systems hypothesis (TVSH) postulates that memory-guided movements rely on intact functions of the ventral stream. Its particular importance for memory-guided actions was initially inferred from behavioral dissociations in the well-known patient DF. Despite of rather accurate reaching and grasping movements to visible targets, she demonstrated grossly impaired memory-guided grasping as much as impaired memory-guided reaching. These dissociations were later complemented by apparently reversed dissociations in patients with dorsal damage and optic ataxia. However, grasping studies in DF and optic ataxia patients differed with respect to the retinotopic position of target objects, questioning the interpretation of the respective findings as a double dissociation. In contrast, the findings for reaching errors in both types of patients came from similar peripheral target presentations. However, new data on brain structural changes and visuomotor deficits in DF also questioned the validity of a double dissociation in reaching. A severe visuospatial short-term memory deficit in DF further questioned the specificity of her memory-guided reaching deficit. Therefore, we compared movement accuracy in visually-guided and memory-guided reaching in a new patient who suffered a confined unilateral damage to the ventral visual system due to stroke. Our results indeed support previous descriptions of memory-guided movements\' inaccuracies in DF. Furthermore, our data suggest that recently discovered optic-ataxia like misreaching in DF is most likely caused by her parieto-occipital and not by her ventral stream damage. Finally, multiple visuospatial memory measurements in HWS suggest that inaccuracies in memory-guided reaching tasks in patients with ventral damage cannot be explained by visuospatial short-term memory or perceptual deficits, but by a specific deficit in visuomotor processing.

Patient D.F. has a profound and enduring visual form agnosia due to a carbon monoxide poisoning episode suffered in 1988. Her inability to distinguish simple geometric shapes or single alphanumeric characters can be attributed to a bilateral loss of cortical area LO, a loss that has been well established through structural and functional fMRI. Yet despite this severe perceptual deficit, D.F. is able to \"guess\" remarkably well the identity of whole words. This paradoxical finding, which we were able to replicate more than 20 years following her initial testing, raises the question as to whether D.F. has retained specialized brain circuitry for word recognition that is able to function to some degree without the benefit of inputs from area LO. We used fMRI to investigate this, and found regions in the left fusiform gyrus, left inferior frontal gyrus, and left middle temporal cortex that responded selectively to words. A group of healthy control subjects showed similar activations. The left fusiform activations appear to coincide with the area commonly named the visual word form area (VWFA) in studies of healthy individuals, and appear to be quite separate from the fusiform face area (FFA). We hypothesize that there is a route to this area that lies outside area LO, and which remains relatively unscathed in D.F.

Investigators study the kinematics of grasping movements (prehension) under a variety of conditions to probe visuomotor function in normal and brain-damaged individuals. \"Natural\" prehensile acts are directed at the goal object and are executed using real-time vision. Typically, they also entail the use of tactile, proprioceptive, and kinesthetic sources of haptic feedback about the object (\"haptics-based object information\") once contact with the object has been made. Natural and simulated (pantomimed) forms of prehension are thought to recruit different cortical structures: patient DF, who has visual form agnosia following bilateral damage to her temporal-occipital cortex, loses her ability to scale her grasp aperture to the size of targets (\"grip scaling\") when her prehensile movements are based on a memory of a target previewed 2 s before the cue to respond or when her grasps are directed towards a visible virtual target but she is denied haptics-based information about the target. In the first of two experiments, we show that when DF performs real-time pantomimed grasps towards a 7.5 cm displaced imagined copy of a visible object such that her fingers make contact with the surface of the table, her grip scaling is in fact quite normal. This finding suggests that real-time vision and terminal tactile feedback are sufficient to preserve DF\'s grip scaling slopes. In the second experiment, we examined an \"unnatural\" grasping task variant in which a tangible target (along with any proxy such as the surface of the table) is denied (i.e., no terminal tactile feedback). To do this, we used a mirror-apparatus to present virtual targets with and without a spatially coincident copy for the participants to grasp. We compared the grasp kinematics from trials with and without terminal tactile feedback to a real-time-pantomimed grasping task (one without tactile feedback) in which participants visualized a copy of the visible target as instructed in our laboratory in the past. Compared to natural grasps, removing tactile feedback increased RT, slowed the velocity of the reach, reduced in-flight grip aperture, increased the slopes relating grip aperture to target width, and reduced the final grip aperture (FGA). All of these effects were also observed in the real time-pantomime grasping task. These effects seem to be independent of those that arise from using the mirror in general as we also compared grasps directed towards virtual targets to those directed at real ones viewed directly through a pane of glass. These comparisons showed that the grasps directed at virtual targets increased grip aperture, slowed the velocity of the reach, and reduced the slopes relating grip aperture to the widths of the target. Thus, using the mirror has real consequences on grasp kinematics, reflecting the importance of task-relevant sources of online visual information for the programming and updating of natural prehensile movements. Taken together, these results provide compelling support for the view that removing terminal tactile feedback, even when the grasps are target-directed, induces a switch from real-time visual control towards one that depends more on visual perception and cognitive supervision. Providing terminal tactile feedback and real-time visual information can evidently keep the dorsal visuomotor system operating normally for prehensile acts.

Identifying the movements of those around us is fundamental for many daily activities, such as recognizing actions, detecting predators, and interacting with others socially. A key question concerns the neurobiological substrates underlying biological motion perception. Although the ventral \"form\" visual cortex is standardly activated by biologically moving stimuli, whether these activations are functionally critical for biological motion perception or are epiphenomenal remains unknown. To address this question, we examined whether focal damage to regions of the ventral visual cortex, resulting in significant deficits in form perception, adversely affects biological motion perception. Six patients with damage to the ventral cortex were tested with sensitive point-light display paradigms. All patients were able to recognize unmasked point-light displays and their perceptual thresholds were not significantly different from those of three different control groups, one of which comprised brain-damaged patients with spared ventral cortex (n > 50). Importantly, these six patients performed significantly better than patients with damage to regions critical for biological motion perception. To assess the necessary contribution of different regions in the ventral pathway to biological motion perception, we complement the behavioral findings with a fine-grained comparison between the lesion location and extent, and the cortical regions standardly implicated in biological motion processing. This analysis revealed that the ventral aspects of the form pathway (e.g., fusiform regions, ventral extrastriate body area) are not critical for biological motion perception. We hypothesize that the role of these ventral regions is to provide enhanced multiview/posture representations of the moving person rather than to represent biological motion perception per se.

Patient D.F. has a profound and enduring visual form agnosia due to a carbon monoxide poisoning episode suffered in 1988. Her inability to distinguish simple geometric shapes or single alphanumeric characters can be attributed to a bilateral loss of cortical area LO, a loss that has been well established through structural and functional fMRI. Yet despite this severe perceptual deficit, D.F. is able to \"guess\" remarkably well the identity of whole words. This paradoxical finding, which we were able to replicate more than 20 years following her initial testing, raises the question as to whether D.F. has retained specialized brain circuitry for word recognition that is able to function to some degree without the benefit of inputs from area LO. We used fMRI to investigate this, and found regions in the left fusiform gyrus, left inferior frontal gyrus, and left middle temporal cortex that responded selectively to words. A group of healthy control subjects showed similar activations. The left fusiform activations appear to coincide with the area commonly named the visual word form area (VWFA) in studies of healthy individuals, and appear to be quite separate from the fusiform face area (FFA). We hypothesize that there is a route to this area that lies outside area LO, and which remains relatively unscathed in D.F.

Patient DF, who developed visual form agnosia following ventral-stream damage, is unable to discriminate the width of objects, performing at chance, for example, when asked to open her thumb and forefinger a matching amount. Remarkably, however, DF adjusts her hand aperture to accommodate the width of objects when reaching out to pick them up (grip scaling). While this spared ability to grasp objects is presumed to be mediated by visuomotor modules in her relatively intact dorsal stream, it is possible that it may rely abnormally on online visual or haptic feedback. We report here that DF\'s grip scaling remained intact when her vision was completely suppressed during grasp movements, and it still dissociated sharply from her poor perceptual estimates of target size. We then tested whether providing trial-by-trial haptic feedback after making such perceptual estimates might improve DF\'s performance, but found that they remained significantly impaired. In a final experiment, we re-examined whether DF\'s grip scaling depends on receiving veridical haptic feedback during grasping. In one condition, the haptic feedback was identical to the visual targets. In a second condition, the haptic feedback was of a constant intermediate width while the visual target varied trial by trial. Despite this incongruent feedback, DF still scaled her grip aperture to the visual widths of the target blocks, showing only normal adaptation to the false haptically-experienced width. Taken together, these results strengthen the view that DF\'s spared grasping relies on a normal mode of dorsal-stream functioning, based chiefly on visual feedforward processing.

It has been suggested that while movements directed at visible targets are processed within the dorsal stream, movements executed after delay rely on the visual representations of the ventral stream (Milner & Goodale, 2006). This interpretation is supported by the observation that a patient with ventral stream damage (D.F.) has trouble performing accurate movements after a delay, but performs normally when the target is visible during movement programming. We tested D.F.\'s visuomotor performance in a letter-posting task whilst varying the amount of visual feedback available. Additionally, we also varied whether D.F. received tactile feedback at the end of each trial (posting through a letter box vs posting on a screen) and whether environmental cues were available during the delay period (removing the target only vs suppressing vision completely with shutter glasses). We found that in the absence of environmental cues patient D.F. was unaffected by the introduction of delay and performed as accurately as healthy controls. However, when environmental cues and vision of the moving hand were available during and after the delay period, D.F.\'s visuomotor performance was impaired. Thus, while healthy controls benefit from the availability of environmental landmarks and/or visual feedback of the moving hand, such cues seem less beneficial to D.F. Taken together our findings suggest that ventral stream damage does not always impact the ability to make delayed movements but compromises the ability to use environmental landmarks and visual feedback efficiently.

BACKGROUND: Patients who have difficulties recognising visual form stimuli are usually labelled as having visual agnosia. However, recent studies let us identify different clinical manifestations corresponding to discrete diagnostic entities which reflect a variety of deficits along the continuum of cortical visual processing.
METHODS: We reviewed different clinical cases published in medical literature as well as proposals for classifying deficits in order to provide a global perspective of the subject. Here, we present the main findings on the neuroanatomical basis of visual form processing and discuss the criteria for evaluating processing which may be abnormal. We also include an inclusive diagram of visual form processing deficits which represents the different clinical cases described in the literature. Lastly, we propose a boosted decision tree to serve as a guide in the process of diagnosing such cases.
CONCLUSIONS: Although the medical community largely agrees on which cortical areas and neuronal circuits are involved in visual processing, future studies making use of new functional neuroimaging techniques will provide more in-depth information. A well-structured and exhaustive assessment of the different stages of visual processing, designed with a global view of the deficit in mind, will give a better idea of the prognosis and serve as a basis for planning personalised psychostimulation and rehabilitation strategies.