Neurobiological Models of Visuospatial Cognition in Children With Williams Syndrome: Measures of Dorsal-Stream and Frontal Function

We examine hypotheses for the neural basis of the profile of visual cognition in young children with Williams syndrome (WS). These are: (a) that it is a consequence of anomalies in sensory visual processing, (b) that it is a deficit of the dorsal relative to the ventral cortical stream, (c) that it reflects deficit of frontal function, in particular of frontoparietal interaction, and (d) that it is related to impaired function in the right hemisphere relative to the left. The tests reported here are particularly relevant to hypotheses 2 and 3. They form part of a more extensive program of investigating visual, visuospatial, and cognitive function in large group of children with WS children, aged 8 months to 15 years. To compare performance across tests, avoiding floor and ceiling effects, we have measured performance in children with WS in terms of the "age equivalence" for typically developing children. In this article the relation between dorsal and ventral function is tested by motion and form coherence thresholds, respectively. We confirm the presence of a subgroup of children with WS who perform particularly poorly on the motion (dorsal) task. However, such performance is also characteristic of normally developing children up to 5 years; thus the WS performance may reflect an overall persisting immaturity of visuospatial processing that is particularly evident in the dorsal stream. Looking at the performance on the global coherence tasks of the entire WS group, we find that there is also a subgroup who have both high form and motion coherence thresholds, relative to the performance of children of the same chronological age and verbal age on the British Picture Vocabulary Scale, suggesting a more general global processing deficit.     

Neurobiological models of visuospatial cognition in children with Williams syndrome: measures of dorsal-stream and frontal function

We examine hypotheses for the neural basis of the profile of visual cognition in young children with Williams syndrome (WS).These are:(a)that it is a consequence of anomalies in sensory visual processing,(b)that it is a de.cit of the dorsal relative to the ventral cortical stream,(c)that it reflects de.cit of frontal function, in particular of frontoparietal interaction, and (d)that it is related to impaired function in the right hemisphere relative to the left. The tests reported here are particularly relevant to hypotheses 2 and 3.They form part of a more extensive program of investigating visual, visuospatial, and cognitive function in large group of children with WS children, aged 8 months to 15 years. To compare performance across tests, avoiding floor and ceiling effects, we have measured performance in children with WS in terms of the "age equivalence " for typically developing children. In this article the relation between dorsal and ventral function is tested by motion and form coherence thresholds, respectively. We confirm the presence of a subgroup of children with WS who perform particularly poorly on the motion (dorsal) task. However, such performance is also characteristic of normally developing children up to 5 years; thus the WS performance may reflect an overall persisting immaturity of visuospatial processing that is particularly evident in the dorsal stream. Looking at the performance on the global coherence tasks of the entire WS group, we find that there is also a subgroup who have both high form and motion coherence thresholds, relative to the performance of children of the same chronological age and verbal age on the British Picture Vocabulary Scale, suggesting a more general global processing deficit. Frontal function was tested by a counterpointing task, ability to retrieve a ball from a "detour box," and the Stroop--like "day.night " task, all of which require inhibition of a familiar response. When considered in relation to overall development as indexed by vocabulary, the day.night task shows little specific impairment, the detour box shows a significant delay relative to controls,and the counterpointing task shows a marked and persistent deficit in many children. We conclude that frontal control processes show most impairment in WS when they are associated with spatially directed responses, reflecting a deficit of frontoparietal processing. However, children with WS may successfully reduce the effect of this impairment by verbally mediated strategies. On all these tasks we find a range of difficulties across individual children and a small subset of children with WS who show very good performance, equivalent to chronological age norms of typically developing children. Overall, we conclude that children with WS have specific processing difficulties with tasks involving frontoparietal circuits within the spatial domain. However, some children with WS can achieve similar performance to typically developing children on some tasks involving the dorsal stream although the strategies and processing may be different in the 2 groups.     

Visual processing in Noonan syndrome: dorsal and ventral stream sensitivity

Global spatial and motion processing abilities were assessed in 18 patients with Noonan syndrome (NS) and in 43 matched controls using form and motion coherence testing, respectively. We observed a discrepancy between the two groups since the study group had significantly lower performances than the control group for form coherence while there was no impairment on motion coherence. All the patients were also assessed on the Movement Assessment Battery for Children (M-ABC) to evaluate visuomotor skills. Thirteen of the 18 (72%) also had global poor performances on the M-ABC. The results show that children with NS have a specific impairment in the global processing of visuospatial information and are likely to have a specific ventral stream deficit as also suggested by the frequent visuomotor perceptual difficulties. Testing form and motion coherence thresholds may be a useful diagnostic tool for this group of patients, despite their normal cognitive abilities, since aspects of global form processing and visuomotor perceptual difficulties can be identified and potentially targeted for a specific rehabilitation program.     

Applying Transcranial Magnetic Stimulation (TMS) Over the Dorsal Visual Pathway Induces Schizophrenia-like Disruption of Perceptual Closure

Perceptual closure ability is postulated to depend upon rapid transmission of magnocellular information to prefrontal cortex via the dorsal stream. In contrast, illusory contour processing requires only local interactions within primary and ventral stream visual regions, such as lateral occipital complex. Schizophrenia is associated with deficits in perceptual closure versus illusory contours processing that is hypothesized to reflect impaired magnocellular/dorsal stream. Perceptual closure and illusory contours performance was evaluated in separate groups of 12 healthy volunteers during no TMS, and during repetitive 10 Hz rTMS stimulation over dorsal stream or vertex (TMS-vertex). Perceptual closure and illusory contours were performed in 11 schizophrenia patients, no TMS was applied in these patients. TMS effects were evaluated with repeated measures ANOVA across treatments. rTMS significantly increased perceptual closure identification thresholds, with significant difference between TMS-dorsal stream and no TMS. TMS-dorsal stream also significantly reduced perceptual closure but not illusory contours accuracy. Schizophrenia patients showed increased perceptual closure identification thresholds relative to controls in the no TMS condition, but similar to controls in the TMS-dorsal stream condition. Conclusions of this study are that magnocellular/dorsal stream input is critical for perceptual closure but not illusory contours performance, supporting both trickledown theories of normal perceptual closure function, and magnocellular/dorsal stream theories of visual dysfunction in schizophrenia.     

Are poor mathematics skills associated with visual deficits in temporal processing?

Developmental learning disabilities such as dyslexia and dyscalculia have a high rate of co-occurrence in pediatric populations, suggesting that they share underlying cognitive and neurophysiological mechanisms. Dyslexia and other developmental disorders with a strong heritable component have been associated with reduced sensitivity to coherent motion stimuli, an index of visual temporal processing on a millisecond time-scale. Here we examined whether deficits in sensitivity to visual motion are evident in children who have poor mathematics skills relative to other children of the same age. We obtained psychophysical thresholds for visual coherent motion and a control task from two groups of children who differed in their performance on a test of mathematics achievement. Children with math skills in the lowest 10% in their cohort were less sensitive than age-matched controls to coherent motion, but they had statistically equivalent thresholds to controls on a coherent form control measure. Children with mathematics difficulties therefore tend to present a similar pattern of visual processing deficit to those that have been reported previously in other developmental disorders. We speculate that reduced sensitivity to temporally defined stimuli such as coherent motion represents a common processing deficit apparent across a range of commonly co-occurring developmental disorders.     

The behavioral phenotype of Williams syndrome: A recognizable pattern of neurodevelopment

Williams syndrome (WS), caused by hemizygous deletion of 1.55-1.8?Mb of chromosome 7q11.23, has a recognizable behavior phenotype that is an important diagnostic sign. Individuals with WS are overly friendly, gregarious, empathetic, and loquacious, but have difficulty interpreting social cues and in making and keeping friends. The neurodevelopmental profile is characterized by overall intellectual disability, strength in concrete language, weakness in visuospatial construction, difficulties with sensory modulation, balance, and tool use, and problems with attention and anxiety. Structural and functional MRI studies demonstrate that gray matter deficiency in the intraparietal sulcus alters processing of spatial information in the dorsal stream (spatial) visual pathway, likely contributing to the visuospatial construction disability. Deficient regulation of the amygdala by the oribitofrontal cortex appears to underlie both the social disinhibition and the specific phobia common in WS. Continued study of cognition, behavior, neuroanatomy, and function in WS will continue to elucidate the neurogenetic underpinnings of human behavior.     

Dissociating the roles of dorsal and ventral CA1 for the temporal processing of spatial locations, visual objects, and odors

The differential contributions of the dorsal and ventral hippocampus for learning and memory have long been of interest. The present experiments were designed to evaluate the contributions of dorsal CA1 and ventral CA1 for temporal processing. Animals were run on three temporal ordering paradigms: one with visual objects, one with olfactory stimuli, and one with spatial locations. Animals with lesions to dorsal CA1 showed deficits for the temporal ordering of visual objects relative to control animals, and deficits for the temporal ordering of spatial locations relative to control and ventral CA1 lesioned animals. Animals with lesions to ventral CA1 showed deficits for the temporal ordering of olfactory information relative to control and dorsal CA1 lesioned animals, and a mild deficit for the temporal ordering of visual objects relative to control animals, but not as severe as those shown by the dorsal CA1 lesioned animals. These data suggest that dorsal CA1 and ventral CA1 contribute to temporal ordering processes, and that dorsal CA1 and ventral CA1 are dissociable for temporal ordering based upon the nature of the information that is processed.     

An intracranial event-related potential study on transformational apparent motion. Does its neural processing differ from real motion?

How the brain processes visual stimuli has been extensively studied using scalp surface electrodes and magnetic resonance imaging. Using these and other methods, complex gratings have been shown to activate the ventral visual stream, whereas moving stimuli preferentially activate the dorsal stream. In the current study, a first experiment assessed brain activations evoked by complex gratings using intracranial electroencephalography in 10 epileptic patients implanted with subdural electrodes. These stimuli of intermediate levels of complexity were presented in such a way that transformational apparent motion (TAM) was perceived. Responses from both the ventral and the dorsal pathways were obtained. The response characteristics of visual area 4 and the fusiform cortex were of similar amplitudes, suggesting that both ventral areas are recruited for the processing of complex gratings. On the other hand, TAM-induced responses of dorsal pathway areas were relatively noisier and of lower amplitudes, suggesting that TAM does not activate motion-specific structures to the same extent as does real motion. To test this hypothesis, we examined the activity evoked by TAM in comparison to the one produced by real motion in a patient implanted with the same subdural electrodes. Findings demonstrated that neural response to real motion was much stronger than that evoked by TAM, in both the primary visual cortex (V1) and other motion-sensitive areas within the dorsal pathway. These results support the conclusion that apparent motion, even if perceptually similar to real motion, is not processed in a similar manner.     

A tale of two agnosias: Distinctions between form and integrative agnosia

The performance of two patients with visual agnosia was compared across a number of tests examining visual processing. The patients were distinguished by having dorsal and medial ventral extrastriate lesions. While inanimate objects were disadvantaged for the patient with a dorsal extrastriate lesion, animate items are disadvantaged for the patient with the medial ventral extrastriate lesion. The patients also showed contrasting patterns of performance on the Navon Test: The patient with a dorsal extrastriate lesion demonstrated a local bias while the patient with a medial ventral extrastriate lesion had a global bias. We propose that the dorsal and medial ventral visual pathways may be characterized at an extrastriate level by differences in local relative to more global visual processing and that this can link to visually based category-specific deficits in processing.     

A tale of two agnosias: distinctions between form and integrative agnosia

The performance of two patients with visual agnosia was compared across a number of tests examining visual processing. The patients were distinguished by having dorsal and medial ventral extrastriate lesions. While inanimate objects were disadvantaged for the patient with a dorsal extrastriate lesion, animate items are disadvantaged for the patient with the medial ventral extrastriate lesion. The patients also showed contrasting patterns of performance on the Navon Test: The patient with a dorsal extrastriate lesion demonstrated a local bias while the patient with a medial ventral extrastriate lesion had a global bias. We propose that the dorsal and medial ventral visual pathways may be characterized at an extrastriate level by differences in local relative to more global visual processing and that this can link to visually based category-specific deficits in processing.     

Evidence for fast signals and later processing in human V1/V2 and V5/MT+: A TMS study of motion perception

Evidence from human and primate studies suggests that fast visual processing may utilize signals projecting from primary visual cortex (V1) through the dorsal stream, to area V5/MT+ or beyond and subsequently back into V1. This coincides with the arrival of parvocellular signals en route to the ventral pathway and infero-temporal cortex. Such evidence suggests that the dorsal stream region V5/MT+ is activated rapidly through the traditional hierarchical pathway and also via a less-well-established direct signal to V5/MT+ bypassing V1. To test this, 16 healthy humans underwent transcranial magnetic stimulation (TMS) of V1/V2 and V5/MT+ while performing a motion-direction detection task. A three-alternate forced-choice design (left/right motion, stationary) allowed analysis of the quality of errors made, in addition to the more usual performance measures. Transient disruption of V1/V2 and V5/MT+ significantly reduced accuracy when TMS was applied at or near motion onset. Most participants also showed disrupted performance with TMS application over V1/V2 approximately 125 ms post motion onset, and significantly reduced accuracy at 158 ms with V5/MT+ stimulation. The two periods of disruption with V1/V2 TMS are suggestive of feedforward/feedback models, although the earlier period of disruption has not been reported in previous TMS studies. Very early activation of V5/MT+, evidenced by diminished accuracy and reduced perception of motion after TMS may be indicative of a thalamic-extrastriate pathway in addition to the traditionally expected later period of processing. A profound disruption of performance prestimulus onset is more likely to reflect disruption of top-down expectancy than disruption of visual processing.     

Attentional functions in dorsal and ventral simultanagnosia

Whole report of brief letter arrays is used to analyse basic attentional deficits in dorsal and ventral variants of simultanagnosia. Using Bundesen's Theory of Visual Attention (TVA), a number of previous theoretical suggestions are formalised and tested, including primary deficit in processing more than one display element, attentional stickiness, foveal bias, and global weakness of the visual representation. Interestingly, data from two cases, one dorsal and one ventral, show little true deficit in simultaneous perception, or selective deficit in those TVA parameters (short-term memory capacity, attentional weighting) specifically associated with multi-element displays. Instead there is a general reduction in speed of visual processing (processing rate in TVA), effective even for a single display element but compounded when two or more elements compete.     

TMS can reveal contrasting functions of the dorsal and ventral visual processing streams

In order to investigate the functional specificity of the dorsal and ventral visual processing steams we used transcranial magnetic stimulation (TMS) to briefly disrupt one or the other while subjects performed three tasks, involving discrimination of colour or shape or relative position. TMS was delivered over right posterior parietal cortex (PPC) or right lateral occipital (LO) cortex, regions known to have visuo-spatial and object processing properties respectively. LO but not PPC stimulation had a significant effect on reaction time when subjects were asked to make a discrimination of relative shape. PPC stimulation had a significant effect when subjects were asked to discriminate relative position of the same shapes. Stimulation of LO also lengthened reaction times on the position task. There were no effects of stimulation at either site on colour discrimination. Results are discussed within the framework of how the dorsal stream and ventral stream are dissociated following their damage in neurological patients and possible ways in which they may interact in the normal brain.     

What and where in mirror reading

In a combined voxel‐based morphometry and functional magnetic resonance imaging study on the practice of mirror reading, we recently found a shift of activation from right superior parietal to right dorsal occipital cortex and a corresponding increase of gray matter. We interpreted this shift of activation and the corresponding structural changes as a shift from effortful visuospatial transformation to a more direct processing of mirrored words ( Ilg et al., 2008 ). To test this hypothesis, we now analyzed brain activation patterns associated with different aspects of mirror reading. Activation at the dorsal occipital cortex and bilateral parietal cortex (dorsal visual stream) was related to inverse text processing, whereas activation of areas at the inferior and ventral occipitotemporal cortex (ventral visual stream) was associated with decoding of mirrored words. This indicates that the dichotomy of content‐related (“what”) and process‐related (“where”) higher visual functions also applies to mirror reading.     

Dorsal and ventral visual stream contributions to perception-action interactions during pointing

The Ebbinghaus illusion, in which a central circle surrounded by large circles appears to be smaller than a central circle surrounded by small circles, affects the speed of pointing movements. When the central circle appears to be big, pointing movements directed towards it are faster than when the central circle appears to be small. This effect could be due to an interaction between ventral stream processing associated with determining relative object size and dorsal stream processing associated with sensorimotor output. Alternatively, the dorsal stream alone could mediate the effect via the transformation of object shape representations into motor output within the parietal lobe. Finally, ventral stream processing could be integrated into motor output through projections to the prefrontal cortex and subsequently to the motor areas of the cortex, thus bypassing the dorsal stream. These three alternatives were tested by disrupting either the ventral or dorsal stream processing using transcranial magnetic stimulation (TMS) while subjects made pointing movements as quickly and accurately as possible to the central target circles within the Ebbinghaus illusion display. The relative changes in reaction time, movement speed, and movement accuracy for small versus large appearing target circles were compared when TMS was delivered over each site as well as at a control site (SMA). The results showed that TMS over either the dorsal or ventral stream but not the SMA reduced the influence of the illusion on the pointing movement speed but did not affect reaction time or movement accuracy. A second control experiment was completed in which TMS was delivered during pointing movements to target circles of physically different sizes that were not surrounded by either large or small circles. This allowed us to determined whether the effect we observed in the main experiment was due specifically to the relative size information contained within the illusory display and the effect this has on the preparation of pointing responses or to an influence on basic perceptual and sensorimotor processes occurring within the ventral and dorsal streams, respectively. The results showed that the affect on pointing movement speed was still present with dorsal but not ventral stream stimulation. Taken together, this evidence suggests that the ventral stream contributes to pointing movements based on relative object size information via its projections to the prefrontal areas and not necessarily through interactions with the dorsal stream.     

Children with williams syndrome: Is there a single neuropsychological profile?

Williams Syndrome (WS) is a rare genetic condition characterized by mental retardation, typical facial dysmorphology, and several medical anomalies. A specific neuropsychological profile with both proficient abilities in language and face recognition and severe difficulties in other visuospatial tasks has been hypothesized in children with WS. This cognitive‐linguistic profile has emerged through comparisons of WS participants with other populations with a similar degree of mental retardation. In this article, performance by WS participants is compared with that of younger normally developing children on linguistic and visuospatial tasks. Results show that the participants included in our study obtained very different profiles in their neuropsychological performance. Overall our results seem to support the hypothesis that children with WS have a complex neuropsychological profile characterized by atypical developments in both the cognitive and the linguistic domain.     

Low level Visual Processing Skills of Adults and Children with Dyslexia

Previous work by Lovegrove and colleagues Lovegrove Martin Slaghuis 1986 suggested that dyslexic children show visual deficits specific to transient processing We designed and examined a number of threshold and suprathreshold tasks to test the generality of their claims We first compared the performance of adult dyslexics and child dyslexics to the performance of age matched normal readers on a series of threshold flicker tasks In contrast to the earlier results dyslexics and normal readers did not differ in their contrast thresholds for flickering sinewave gratings Dyslexic children and normal readers also showed similar performance on two suprathreshold visual search tasks that evaluated transient processing The evidence suggests that a transient processing deficit is not a general characteristic of developmental dyslexia Claims that visual factors play a role in dyslexia must address the confounding role of performance and attentional factors     

Neural Representations of Visual Words and Objects: A Functional MRI Study on the Modularity of Reading and Object Processing

There have been several studies supporting the notion of a ventral-dorsal distinction in the primate cortex for visual object processing, whereby the ventral stream specializes in object identification, and the dorsal stream is engaged during object localization and interaction. There is also a growing body of evidence supporting a ventral stream that specializes in lexical (i.e., whole-word) reading, and a dorsal stream that is engaged during sub-lexical reading (i.e., phonetic decoding). Here, we consider the extent to which word-reading processes are located in regions either intersecting with, or unique from, regions that sub-serve object processing along these streams. Object identification was contrasted with lexical-based reading, and object interaction processing (i.e., deciding how to interact with an object) was contrasted with sub-lexical reading. Our results suggest that object identification and lexical-based reading are largely ventral and modular, showing mainly unique regions of activation (parahippocampal and occipital-temporal gyri function associated with object identification, and lingual, lateral occipital, and posterior inferior temporal gyri function associated with lexical-based reading) and very little shared activation (posterior inferior frontal gyrus). Object interaction processing and phonetic decoding are largely dorsal, and show both modular regions of activation (more lateralized to the dorsal-frontal right hemisphere for pseudohomophone naming, and more to the dorsal-frontal left hemisphere for the object interaction task) as well as significant shared regions of processing (precentral gyri, left inferior frontal cortex, left postcentral gyrus, left lateral occipital cortex, and superior posterior temporal gyri). Given that the perceptual experimental conditions show primarily modular and very little shared processing, whereas the analytical conditions show both substantial modular and shared processing, we discuss a reconsideration of “modularity of mind” which involves a continuum between strictly modular processing and varying degrees of shared processing, and which also depends on the nature of the tasks compared (i.e., perceptual versus analytical).     

Orientation coding: a specific deficit in Williams syndrome?

Williams syndrome (WS) is a rare genetic disorder with a unique cognitive profile in which verbal abilities are markedly stronger than visuospatial abilities. This study investigated the claim that orientation coding is a specific deficit within the visuospatial domain in WS. Experiment 1 employed a simplified version of the Benton Judgement of Line Orientation task and a control, length-matching task. Results demonstrated comparable levels of orientation matching performance in the group with WS and a group of typically developing (TD) controls matched by nonverbal ability, although it is possible that floor effects masked group differences. A group difference was observed in the length-matching task due to stronger performance from the control group. Experiment 2 employed an orientation-discrimination task and a length-discrimination task. Contrary to previous reports, the results showed that individuals with WS were able to code by orientation to a comparable level as that of their matched controls. This demonstrates that, although some impairment is apparent, orientation coding does not represent a specific deficit in WS. Comparison between Experiments 1 and 2 suggests that orientation coding is vulnerable to task complexity. However, once again, this vulnerability does not appear to be specific to the population with WS, as it was also apparent in the TD controls.     

Intact automatic avoidance of obstacles in patients with visual form agnosia

In everyday life our reaching behaviour has to be guided not only by the location and properties of the target object, but also by the presence of potential obstacles in the workspace. Recent evidence from neglect and optic ataxia patients has suggested that this automatic obstacle avoidance is mediated by the dorsal, rather than the ventral, stream of visual processing. We tested this idea in two studies involving patients with visual form agnosia resulting from bilateral ventral-stream damage. In the first study, we asked patient DF to reach out and pick up a target object in the presence of obstacles placed at varying distances to the left or right of the target. We found that both DF and controls shifted their trajectories away from the potential obstacles and adjusted their grip aperture in such a way as to minimize risk of collision. In a second study, we asked DF and a second patient, SB, to either reach between, or to bisect the space between, two cylinders presented at varying locations. We found that both patients adjusted their reach trajectories to account for shifts in cylinder location in the reaching task, despite showing significantly worse performance than control subjects when asked to make a bisection judgement. Taken together, these data indicate that automatic obstacle avoidance behaviour is spared in our patients with visual form agnosia. We attribute their ability to the functional intactness of the dorsal stream of visual processing, and argue that the ventral stream plays no important role in automatic obstacle avoidance.