Temporal lobe contribution to perceptual function: A tale of three patient groups.

There has been growing recognition of the contribution of medial and anterior temporal lobe structures to non-mnemonic functions, such as perception. To evaluate the nature of this contribution, we contrast the perceptual performance of three patient groups, all of whom have a perturbation of these temporal lobe structures. Specifically, we compare the profile of patients with focal hippocampal (HC) lesions, those with more extensive lesions to the medial temporal lobe (MTL) that include HC and perirhinal cortex (PrC), and those with congenital prosopagnosia (CP), whose deficit has been attributed to the disconnection of the anterior temporal lobe from more posterior structures. All participants completed a range of'oddity' tasks in which, on each trial, they determined which of four visual stimuli in a display was the'odd-one-out'. There were five stimulus categories including faces, scenes, objects (high and low ambiguity) and squares of different sizes. Comparisons were conducted separately for the HC, MTL and CP groups against their matched control groups and then the group data were compared to each other directly. The group profiles were easily differentiable. Whereas the HC group stood out for its difficulty in discriminating scenes and the CP group stood out for its disproportionate difficulty in discriminating faces with milder effects for scenes and high ambiguity objects, the MTL group evinced a more general discrimination deficit for faces, scenes and high ambiguity objects. The group differences highlight distinct profiles for each of the three groups and distinguish the signature perceptual impairments following more extended temporal lobe alterations. In the recent reconsideration of the role of the hippocampus and neocortex, Moscovitch and colleagues (Moscovitch et al., 2016) note that the medial temporal lobe structures play a role in non-mnemonic functions, such as perception, problem solving, decision-making and language. Here, we address this exact issue, specifically with respect to perception, and we dedicate this paper to Morris Moscovitch in recognition of his profound contribution to science, to his students and to his colleagues.

Recombinant expression of coagulation factor VIII in hepatic and non-hepatic cell lines stably transduced with third generation lentiviral vectors comprising the minimal factor VIII promoter.

BACKGROUND: Lentiviral vectors have the capacity to transduce stably non-dividing, differentiated and undifferentiated cells of various tissues, including liver. To obtain high-level expression of transgenes, vectors often rely on viral promoters. However, recent data suggest that the supraphysiologic expression from ubiquitous viral promoters may not be beneficial and harbor the risk of oncogene activation. Therefore this study explored the lentiviral-mediated expression of human coagulation factor VIII (FVIII) driven by the physiologic FVIII gene promoter (FVIII-p), the liver-specific human alpha-1-antitrypsin gene promoter (hAAT-p), the ubiquitous but non-viral EF1alpha promoter (EF1alpha-p) and the viral CMV promoter. METHODS: Hepatic and non-hepatic cell lines were stably transduced with lentiviral vectors encoding FVIIIdelB and EGFP. To compare the different promoters, lentiviral vectors were cloned to drive FVIII expression from FVIII-p, EF1alpha-p, hAAT-p and CMV-p. RESULTS: As expected, the strong viral CMV-p and the ubiquitous EF1alpha-p resulted in the highest FVIII expression in all cell lines tested (CMV-p 1.85 IU/mL/10(6) cells for 293T, 3.15 for HepG2, 5.03 for SK-Hep, 0.91 for Hepa1-6; EF1-alpha promoter 0.30 IU/mL/10(6) cells for 293T, 0.04 for HepG2, 2.75 for SK-Hep, 0.46 for Hepa1-6). While the hAAT-p resulted in low FVIII levels (0.10 IU/mL/10(6)cells in HepG2 and 0.04 in Hepa1-6), the FVIII promoter gave reasonable expression levels in hepatic cells (0.47 IU/mL/10(6)cells in Hepa1-6 and 0.44 in SK-Hep). DISCUSSION: These results indicate the potential usefulness of the FVIII-p for hemophilia A gene therapy.

Patient Schn: has Goldstein and Gelb's case withstood the test of time?

The current manuscript takes a critical look at the case of Goldstein and Gelb's patient, Schn, reported to be the first well-defined example of apperceptive visual agnosia. While doubts have been cast on the validity of the original investigations, we propose that perhaps the case of Schn should be reclassified as an example of integrative agnosia. Be that as it may, what is not in doubt is that the case of Schn has had a lasting impact on the development of neuropsychological theorem.

Hemispatial neglect: its effects on visual perception and visually guided grasping.

Hemispatial neglect is a neurological disorder characterized by a failure to represent information appearing in the hemispace contralateral to a brain lesion. In addition to the perceptual consequences of hemispatial neglect, several authors have reported that hemispatial neglect impairs visually guided movements. Others have reported that the extent of the impairment depends on the type of visually guided task. Finally, in some cases, neglect has been shown to impair visual perception without affecting visuomotor control in relation to the very same stimuli. While neglect patients may be able to successfully pick up an object they have difficulty perceiving in its entirety, it does not mean that they are picking up the object in the same way that a neurologically intact individual would. In the current study, patients with hemispatial neglect were presented with irregularly shaped objects, directly in front of them, that lacked clear symmetry and required an analysis of their entire contour in order to calculate stable grasp points. In a perceptual discrimination task, the neglect patients had difficulty distinguishing one object from another on the basis of their shape. In a grasping task, the neglect patients showed more variance in the position of their grasp on the target objects than their control subjects, with an overall shift to the relative right side of the presented objects. The perceptual and visuomotor deficits seen in patients with hemispatial neglect deficits may be the result of an inability to form good structural representations of the entire object for use in visual perception and visuomotor control.

The effects of rotation and inversion on face processing in prosopagnosia.

The current study investigated the sensitivity of face recognition to two changes of the stimulus, a rotation in depth and an inversion, by comparing the performance of two prosopagnosic patients, RN and CR, with non-neurological control subjects on a face-matching task. The control subjects showed an effect of depth rotation, with errors and reaction times increasing systematically with rotation angle, and the traditional inversion effect, with errors and reaction times increasing under inverted conditions. In contrast, RN showed no effect of rotation or inversion on his error data but did show a less sensitively graded effect of rotation and the traditional inversion effect on reaction times. CR did not show a graded effect of rotation on his errors or reaction times. Although CR showed the traditional inversion effect on his error data, he displayed an inversion superiority effect on his reaction time data, which supports the claim that the damaged holistic processing systems continue to dominate face processing in prosopagnosia even though they are malfunctioning. These results suggest that the damage that occurs to the ventral temporal cortex in prosopagnosia may have forced the patients to rely on sources of information that are not dependent on the view of the face and, moreover, cannot be adapted to deal with rotated faces under both upright and inverted conditions.

Oculographic analysis of word reading in hemispatial neglect.

Neglect dyslexia is a disorder in which individuals misread text appearing on the contralateral side of space following an acquired lesion, usually to the right parietal lobe. This disorder is generally attributed to an impairment in representing spatial information. To determine whether the spatial representations underlying reading differ from those mediating other forms of visual behavior, we investigated the co-occurrence of neglect dyslexia with that of neglect, which manifests on tasks such as line bisection or line cancellation. We also examined the correlation between neglect dyslexia, when present, and eye movements in order to characterize the neglect dyslexia disorder further. Whereas there is no clear relationship between the reading disorder and other symptoms of visuospatial neglect, suggesting segregated spatial representations, there is a direct correspondence between the oculomotor performance of patients with neglect dyslexia and their reading behavior. This latter result suggests that the reading deficit may well arise from the failure to register and perceive the contralesional information.

Cued visual attention does not distinguish between occluded and occluding objects.

Does visual attention spread from the cued end of an occluded object to locations occupied by inferred portions of that object? We investigated this question by using a probe detection paradigm with two-dimensional (2-D) displays of occluded objects. Probes could appear in occluded or nonoccluded locations on either a cued or noncued object. Participants responded faster to probes appearing within the region of space occupied by the cued object. This was true not only when the probe appeared in positions separated from the cued location by an occluder (as demonstrated by Moore, Yantis, & Vaughan, 1998), but also when it appeared in positions on the occluder itself. Thus, results suggest that cued facilitation spreads to regions of noncued occluding objects that overlap cued occluded objects in 2-D space.

The eye movements of pure alexic patients during reading and nonreading tasks.

We compared the eye-movements of two patients who read letter-by-letter (LBL) following a left occipital lobe lesion with those of normal control subjects and of hemianopic patients in two tasks: a nonreading visual search task and a text reading task. Whereas the LBL readers exhibited similar eye-movement patterns to those of the other two groups on the nonreading task, their eye movements differed significantly during reading, as reflected in the disproportionate increase in the number and duration of fixations per word and in the regressive saccades per word. Importantly, relative to the two control groups, letter-by-letter readers also made more fixations per word as word length increased, especially as word frequency and word imageability decreased. Two critical results emerged from these experiments: First, the alteration in the oculomotor behavior of the LBL readers during reading is similar to that seen in normal readers under difficult reading conditions, as well as in beginning readers and in those with developmental dyslexia, and appears to reflect difficulties in processing the visual stimulus. Second, the interaction of length with frequency and with imageability in determining the eye movement pattern is consistent with an interactive activation model of normal word recognition in which weakened activation of orthographic input can nevertheless engage high-level lexical factors.

A functional MRI study of face recognition in patients with prosopagnosia.

An fMRI investigation was conducted to determine whether patients with impaired face recognition, a deficit known as prosopagnosia, would show functional activation in the fusiform gyrus, the neural substrate for face processing, when viewing faces. While the patients did show activation in the fusiform gyrus, with significantly more voxels in posterior areas than their control subjects, this activation was not sufficient for face processing. In one of the patients, the posterior activation was particularly evident in the left hemisphere, which is thought to be involved in feature-based strategies of face perception. We conclude that an increased reliance on feature-based processing in prosopagnosia leads to a recruitment of neurons in posterior regions of the fusiform gyrus, regions that are not ideally suited for processing faces.

Attending to the parts of a single object: part-based selection limitations.

Studies of object-based attention have demonstrated poorer performance in dividing attention between two objects in a scene than in focusing attention on a single object. However, objects often are composed of several parts, and parts are central to theories of object recognition. Are parts also important for visual attention? That is, can attention be limited in the number of parts processed simultaneously? We addressed this question in four experiments. In Experiments 1 and 2, participants reported two attributes that appeared on the same part or on different parts of a single multipart object. Participants were more accurate in reporting the attributes on the same part than attributes on different parts. This part-based effect was not influenced by the spatial distance between the parts, ruling out a simple spatial attention interpretation of our results. A control study demonstrated that our spatial manipulation was sufficient to observe shifts of spatial attention. This study revealed an effect of spatial distance, indicating that our spatial manipulation was adequate for observing spatial attention. The absence of a distance effect in Experiments 1 and 2 suggests that part-based attention may not rely entirely on simple shifts of spatial attention. Finally, in Experiment 4 we found evidence for part-based attention, using stimuli controlled for the distance between the parts of an object. The results of these experiments indicate that visual attention can selectively process the parts of an object. We discuss the relationship between parts and objects and the locus of part-based attentional selection.

Active control of locomotion facilitates nonvisual navigation.

In some navigation tasks, participants are more accurate if they view the environment beforehand. To characterize the benefits associated with visual previews, 32 blindfolded participants were guided along simple paths and asked to walk unassisted to a specified destination (e.g., the origin). Paths were completed without vision, with or without a visual preview of the environment. Previews did not necessarily improve nonvisual navigation. When previewed landmarks stood near the origin or at off-path locations, they provided little benefit; by contrast, when they specified intermediate destinations (thereby increasing the degree of active control), performance was greatly enhanced. The results suggest that the benefit of a visual preview stems from the information it supplies for actively controlled locomotion. Accuracy in reaching the final destination, however, is strongly contingent upon the destination's location during the preview.

The interaction of spatial reference frames and hierarchical object representations: evidence from figure copying in hemispatial neglect.

In copying or drawing a figure, patients with hemispatial neglect following right parietal lobe lesions typically produce an adequate representation of parts on the right of the figure while omitting the corresponding features on the left. The neglect of information occupying contralateral locations is influenced by multiple spatial reference frames and by the hierarchical structure of the object(s) in the figure. The present work presents a computational characterization of the interaction among these influences to account for the way in which neglect manifests in copying. Empirical data are initially collected from brain-damaged and normal control subjects during two figure-copying tasks in which the hierarchical complexity and orientation of the displays to be copied are manipulated. In the context of the model, neglect is simulated by a "lesion" (monotonic drop-off along gradient from right to left) that can affect performance in both object- and viewer-centered reference frames. The effect of neglect in both these frames, coupled with the hierarchical representation of the object(s), provides a coherent account of the copying behavior of the patients and may be extended to account for the copying performance of other patients across a range of objects and scences.

Updating of locations during whole-body rotations in patients with hemispatial neglect.

Posterior parietal cortex lesions have been associated with both hemispatial neglect and spatial-updating deficits. Currently, the relation between these processes remains poorly understood. We tested the ability of parietal patients with neglect to update remembered target locations during passive whole-body rotations. The rotations and manual pointing responses were executed with and without vision. During the rotation, the remembered location stayed on the same side of the body midline or crossed the midline. Parietal patients generally underestimated rotations, as compared with control groups, but updated targets equally well on either side of the body midline, regardless of the amount of updating required. Once parietal patients have localized a target, they can use self-motion information to update its location, even if it passes into the region they typically neglect. This lack of contralesional updating effects contrasts with impairments in eye position updating found in previous work with parietal patients.

Impaired initiation but not execution of contralesional saccades in hemispatial neglect.

Patients with unilateral neglect are impaired at making saccades to contralesional targets. Whether this problem arises from a deficit in perception, in planning the saccade or in executing the eye movement or some combination thereof remains unclear. We measured several variables related to the initiation and execution of saccades in an experiment which crossed two factors: target side (left, right) and direction of saccade (leftwards, rightwards). Relative to control subjects, patients with left-sided neglect were impaired in planning but not executing the contralesional saccade; while the latency to move their eyes following the onset of the target was increased, the duration and velocity to reach the target were normal. In addition, there were also no directional differences for saccades that were hypometric or inaccurate in the patients, further ruling out an execution impairment. Interestingly, this directional initiation deficit was exaggerated for leftward saccades to left targets, compared with all other conditions. We suggest that the disadvantage for contralesional saccades in neglect patients is attributable to a deficit not only in perceiving contralateral targets but also in planning leftward saccades. Once the saccade is initiated, however, execution apparently proceeds unimpaired.

Phonological activation in pure alexia.

Pure alexia is a reading impairment in which patients appear to read letter-by-letter. This disorder is typically accounted for in terms of a peripheral deficit that occurs early on in the reading system, prior to the activation of orthographic word representations. The peripheral interpretation of pure alexia has recently been challenged by the phonological deficit hypothesis, which claims that a postlexical disconnection between orthographic and phonological information contributes to or is responsible for the disorder. Because this hypothesis was mainly supported by data from a single patient (IH), who also has surface dyslexia, the present study re-examined this hypothesis with another pure alexic patient (EL). In contrast to patient IH, EL did not show any evidence of a phonological deficit. Her pattern of performance in naming was not qualitatively different from that of normal readers; she appeared to be reading via a mode of processing resulting in strong serial and lexical effects, a pattern often observed in normal individuals reading unfamiliar stimuli. The present results do not obviously support the phonological hypothesis and are more consistent with peripheral interpretations of pure alexia. The peripheral and the phonological accounts of pure alexia are discussed in light of two current models of visual word recognition.

Occlusion, symmetry, and object-based attention: reply to Saiki (2000).

J. Saiki (2000) argued that, because the stimuli used by M. Behrmann, R. S. Zemel, and M. C. Mozer (1998) were confounded by symmetry, conclusions about whether amodally completed objects can benefit from object-based attention are unwarranted. Here, the authors examine J. Saiki's claim further and expand on their view of the mechanisms underlying object-based attention, suggesting that perceptual organization is the process whereby features from a single object are selectively attended. In light of this, they claim that heuristics such as symmetry and collinearity play an important role in the facilitation of features from a single object. In support of this claim, they present data from a further experiment using displays that exploit common fate, another grouping heuristic, and show that, under these conditions, the hallmark of object-based attention, a single-object advantage, is obtained for the occluded (amodally completed) shapes.

Selective attention to the parts of an object.

Recent empirical results suggest that there is a decrement in dividing attention between two objects in a scene compared with focusing attention on a single object. However, objects can be made of individual parts. Is there a decrement for dividing attention across different parts of a single object? We addressed this question in two experiments. In Experiment 1, we demonstrated that attention can exhibit part-based selection--that is, the subjects were more accurate in reporting two attributes from the same part of an object than they were in reporting attributes from different parts of an object. In Experiment 2, we demonstrated that part-based attentional decrements occurred simultaneously with object-based attentional decrements. The results from Experiment 2 demonstrated that part-based attention is evident at the same time as objects are processed as coherent whole. Our results imply that there is an attentional mechanism that can select either objects or their parts.

Intact spatial updating during locomotion after right posterior parietal lesions.

One function of the posterior parietal cortex (PPC) is to monitor and integrate sensory signals relating to the current pointing direction of the eyes. We investigated the possibility that the human PPC also contributes to spatial updating during larger-scale behaviors. Two groups of patients with brain injuries either including or excluding the right hemisphere PPC and a group of healthy subjects performed a visually-directed walking task, in which the subject views a target and then attempts to walk to it without vision. All groups walked without vision accurately and precisely to remembered targets up to 6 m away; the patient groups also performed similarly to the healthy controls when indicating egocentric distances using non-motoric responses. These results indicate that the right PPC is not critically involved in monitoring and integrating non-visual self-motion signals, at least along linear paths. In addition, visual perception of egocentric distance in multi-cue environments is immune to injury of a variety of brain areas.

Can face recognition really be dissociated from object recognition?

We argue that the current literature on prosopagnosia fails to demonstrate unequivocal evidence for a disproportionate impairment for faces as compared to nonface objects. Two prosopagnosic subjects were tested for the discrimination of objects from several categories (face as well as nonface) at different levels of categorization (basic, subordinate, and exemplar levels). Several dependent measures were obtained including accuracy, signal detection measures, and response times. The results from Experiments 1 to 4 demonstrate that, in simultaneous-matching tasks, response times may reveal impairments with nonface objects in subjects whose error rates only indicate a face deficit. The results from Experiments 5 and 6 show that, given limited stimulus presentation times for face and nonface objects, the same subjects may demonstrate a deficit for both stimulus categories in sensitivity. In Experiments 7, 8 and 9, a match-to-sample task that places greater demands on memory led to comparable recognition sensitivity with both face and nonface objects. Regardless of object category, the prosopagnosic subjects were more affected by manipulations of the level of categorization than normal controls. This result raises questions regarding neuropsychological evidence for the modularity of face recognition, as well as its theoretical and methodological foundations.

Slowing of reaction time in Parkinson's disease: the involvement of the frontal lobes.

This study investigated the possibility that the previously mixed findings relating to cognitive deficits in Parkinson's disease might be attributable to inhomogeneity within the patients sampled, with attentional deficits occurring only for those Parkinson's patients who also have additional frontal lobe impairment. Twenty-five patients with idiopathic Parkinson's disease were classified as showing frontal dysfunction, or not, on the basis of their performance on the Wisconsin Card Sorting Test and the picture arrangement subtest of the WAIS. The two groups, and a control group of normal elderly subjects matched for age and IQ, undertook tests of visual attention designed to dissociate baseline response speed from central information processing speed. Error rates did not differ between the groups. Performance of the non-frontally impaired Parkinson's group was indistinguishable from that of the controls. By contrast, the 'frontally impaired' Parkinson's group responded significantly more slowly than the controls. Further analyses indicated that for the frontally-impaired Parkinson's group, information processing and automatic functions were unimpaired but there was a generalised slowing (as reflected by increased baseline response time) which may represent a non-specific global cognitive impairment. These findings suggest that the frontal lobes may be implicated in slowed response speed in Parkinson's disease.