Atypical Neuropsychological Profile in a Boy with 22q11.2 Deletion Syndrome Keywords:

In this article the general and specific cognitive impairments of the boy R.H. with a de novo deletion 22q11.2 are described. His full-scale IQ was 73, and he obtained only slightly better verbal than non-verbal subtest scores. Neuropsychological assessment revealed specific impairments in perceptual categorization of objects presented suboptimal, matching of unfamiliar faces, and verbal learning and memory. In contrast, he performed in accordance with his intelligence level on other visual perceptual tasks, on non-verbal learning and memory tasks, and on attention tasks. Voxel-wise statistical comparison of a high-resolution T1-weighted magnetic resonance image of R.H’s brain with similar images obtained from 14 normal control children revealed as major abnormalities a reduction of the right inferior parietal and superior occipital lobe, and a bilateral reduction of deep white matter behind the inferior frontal gyrus. These cognitive impairments and MRI abnormalities are not commonly described in 22q11.2 Deletion Syndrome and may indicate a larger heterogeneity in the neurocognitive phenotype than currently evidenced. At least in this boy the microdeletion seems to have interfered with the development and functioning of particular neural subsystems, while the structure and functioning of other subsystems was left intact.     

Neuropsychological profile and neuroimaging in patients with 22Q11.2 Deletion Syndrome: a review.

22q11.2 Deletion Syndrome is associated with cognitive, behavioural, and psychiatric problems and is known to affect brain structure. Recently, 22q11.2 Deletion Syndrome has been proposed as a disease model for a genetic subtype of schizophrenia. In this paper we discuss the currently available literature on neurocognitive functioning and brain anatomy in patients with 22q11.2 Deletion Syndrome, and how this contributes to our understanding of the neurobiology of schizophrenia. Research on cognitive functioning in 22q11.2 Deletion Syndrome patients suggests a specific cognitive profile with impairments on arithmetical, visuo-spatial, and executive tasks and relatively preserved language skills. Prominent findings of neuroimaging studies in 22q11.2 Deletion Syndrome patients are: reduction of overall brain volume, midline defects, structural alterations of cerebellum and frontal lobe, white matter abnormalities, and decreased grey matter volumes in parietal and temporal areas. We describe how brain abnormalities in patients with 22q11.2 Deletion Syndrome may contribute to the understanding of the clinical syndrome including cognitive impairments, psychotic symptoms, and social and communication problems.     

Selective and sustained attention in children with spina bifida myelomeningocele

This study examined memory functioning in children and adolescents with 22q11.2 Deletion Syndrome (DS; velocardiofacial syndrome). An overall verbal better than nonverbal memory pattern was evident on the Test of Memory and Learning (TOMAL), with children with 22q11.2 DS performing significantly below their siblings and children with low average IQ but similar to children with autism on facial memory. Children with 22q11 DS also performed significantly below their siblings on tests of verbal working memory. Children with autism performed significantly poorer than the siblings of children with 22q11.2 DS only on their recall of stories. Delayed recall was significantly poorer in children with 22q11.2 DS and children with autism, compared to sibling controls. Although there were no significant group differences on tests of multiple trial verbal or visual learning, a relative weakness was noted with multiple trial visual learning in children with 22q11.2 DS and their siblings, suggesting that an alternative or interactive factor other than the deletion may account for the relatively better verbal compared to nonverbal memory abilities. Deficits in facial memory in children with both 22q11.2 DS and autism suggest disruptions in ventral temporal pathways such as between fusiform gyrus and parahippocampal/hippocampal regions whereas deficits in verbal working memory in children with 22q11.2 DS implicates dorsolateral prefrontal regions, both intimating aberrant white matter pathways.     

Memory and learning in children with 22q11.2 deletion syndrome: evidence for ventral and dorsal stream disruption?

This study examined memory functioning in children and adolescents with 22q11.2 Deletion Syndrome (DS; velocardiofacial syndrome). An overall verbal better than nonverbal memory pattern was evident on the Test of Memory and Learning (TOMAL), with children with 22q11.2 DS performing significantly below their siblings and children with low average IQ but similar to children with autism on facial memory. Children with 22q11 DS also performed significantly below their siblings on tests of verbal working memory. Children with autism performed significantly poorer than the siblings of children with 22q11.2 DS only on their recall of stories. Delayed recall was significantly poorer in children with 22q11.2 DS and children with autism, compared to sibling controls. Although there were no significant group differences on tests of multiple trial verbal or visual learning, a relative weakness was noted with multiple trial visual learning in children with 22q11.2 DS and their siblings, suggesting that an alternative or interactive factor other than the deletion may account for the relatively better verbal compared to nonverbal memory abilities. Deficits in facial memory in children with both 22q11.2 DS and autism suggest disruptions in ventral temporal pathways such as between fusiform gyrus and parahippocampal/hippocampal regions whereas deficits in verbal working memory in children with 22q11.2 DS implicates dorsolateral prefrontal regions, both intimating aberrant white matter pathways.     

Differential memory impairment in dementia with Lewy bodies and Alzheimer's disease

This study was conducted in order to elucidate the functioning of the Central Executive System of Working Memory (WM) and to clarify the status of other cognitive functions in Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Fourteen DLB, 22 AD, and 23 control subjects were assessed with the dual task paradigm and other cognitive tests. When compared with controls, DLB subjects performed more poorly in concurrent conditions on semantic WM tasks, and AD subjects performed more poorly on the spatial WM task. The DLB subjects had an inferior verbal span and AD subjects, an inferior recall on the CVLT. These data suggest relative impairments of verbal and semantic WM in DLB and relative impairments of spatial WM and verbal episodic memory in AD.     

Numerical magnitude processing impairments in genetic syndromes: a cross‐syndrome comparison of Turner and 22q11.2 deletion syndromes

Cross‐syndrome comparisons offer an important window onto understanding heterogeneity in mathematical learning disabilities or dyscalculia. The present study therefore investigated symbolic numerical magnitude processing in two genetic syndromes that are both characterized by mathematical learning disabilities: Turner syndrome and 22q11.2 deletion syndrome (22q11DS). We further verified whether the phenotypic outcomes of these syndromes emerged from the same or different cognitive processes and therefore examined whether numerical impairments were related to working memory deficits, often observed in these syndromes. Participants were 24 girls with Turner syndrome, 25 children with 22q11DS and 48 well‐matched typically developing control children. All children completed a symbolic numerical magnitude comparison task and four additional working memory tasks. Both groups of children with genetic syndromes showed similar impairments in symbolic numerical magnitude processing compared to typically developing controls. Importantly, in Turner syndrome, group differences in symbolic numerical magnitude processing disappeared when their difficulties in visual‐spatial working memory were taken into account. In contrast, the difficulties in 22q11DS were not explained by poor visual‐spatial working memory. These data suggest that different factors underlie the symbolic numerical magnitude processing impairments in both patient groups with mathematical learning disabilities and highlight the value of cross‐syndrome comparisons for understanding different pathways to mathematical learning disabilities or dyscalculia.     

The roles of different executive functioning skills in young children’s mental computation and applied mathematical problem-solving

This study investigated the relationships of four executive functioning skills (including verbal working memory, spatial working memory, inhibitory control, and cognitive flexibility) with young children’s mental computation and applied mathematical problem-solving. Two hundred and twenty-five Chinese kindergarteners were tested with a battery of general cognitive, executive functioning and mathematics skills. Results showed that when children’s age, gender, non-verbal intelligence, and listening comprehension skills were controlled, verbal working memory and cognitive flexibility were significant correlates of mental computation, whereas verbal working memory, spatial working memory, and cognitive flexibility were significant correlates of applied mathematical problem-solving. Inhibitory control was not significantly associated with the two domains of mathematics under investigation. The findings highlight the differential roles of different executive functioning skills in early mathematical skills and offer practical implication for helping young children in learning complex mathematical skills.     

Maladaptive conflict monitoring as evidence for executive dysfunction in children with chromosome 22q11.2 deletion syndrome

Using an adaptation of the Attentional Networks Test, we investigated aspects of executive control in children with chromosome 22q11.2 deletion syndrome (DS22q11.2), a common but not well understood disorder that produces non-verbal cognitive deficits and a marked incidence of psychopathology. The data revealed that children with DS22q11.2 demonstrated greater difficulty than controls in locating and processing target items in the presence of distracters. Importantly, children with DS22q11.2 showed a deficit in the ability to monitor and adapt to stimulus conflict. These data provide evidence of inadequate conflict adaptation in children with DS22q11.2, a problem that is also present in schizophrenia. The findings of specific executive dysfunction in this group may provide a linkage between particular genetic abnormalities and the development of psychopathology.     

Susceptibility of spatial and verbal working memory to demands of the central executive

We used a dual-task paradigm to examine the degree to which domain-specific spatial and verbal subsystems depend on the domain-general central executive. Forty participants were asked to retain spatial or verbal information while performing a concurrent secondary task related to simple arithmetic. The secondary tasks consisted of three cognitive processes: single-digit addition, a digit-carrying operation, and digit reading. The single-digit addition and carry operation include central executive functioning, while digit reading relies solely on the phonological loop. The single-digit addition caused a performance decrement on the spatial working memory task, while the digit reading impaired performance on the verbal working memory task. The carry operation interfered with recall accuracy on both working memory tasks. The spatial working memory task was significantly correlated with the verbal working memory task only when the secondary task was more demanding on the central executive. Our results suggest that spatial working memory rather than verbal working memory is susceptible to failure of central executive functioning and that the central executive plays an important role in regulating the cognitive demands of different domains.     

Identifying the nature of impairments in executive functioning and working memory of children with severe difficulties in arithmetic

An age-matched achievement-matched design was used to examine whether the executive functioning and working memory impairments exhibited by children with severe difficulties in arithmetic (SDA) are better viewed as developmental lags or as cognitive deficits. Three groups of children were included: 20 SDA children, 20 typically achieving children (CM) matched in chronological age with the SDA children, and 20 younger typically achieving children (AM) matched in achievement with the SDA group. While children with SDA did not exhibit impairments in color-word inhibition and verbal working memory, they did demonstrate impairments in shifting, quantity-digits inhibition, and visuospatial working memory. As children with SDA did not perform more poorly than their AM counterparts on any of these tasks, impairments in specific areas of executive functioning and working memory appear to reflect developmental lags rather than cognitive deficits.     

Domain specific attentional impairments in children with chromosome 22q11.2 deletion syndrome

One of the defining cognitive characteristics of the chromosome 22q deletion syndrome (DS22q11.2) is visuospatial processing impairments. The purpose of this study was to investigate and extend the specific attentional profile of children with this disorder using both an object-based attention task and an inhibition of return task. A group of children with the disorder was compared in these tasks with a group of age-matched typically developing children. The children with DS22q11.2 demonstrated impaired spatially based orienting which is consistent with previous findings in this group. Strikingly, the children with DS22q11.2 also demonstrated an improved ability to use object-based cues, relative to the typically developing group. Finally, the children with DS22q11.2 demonstrated an intact inhibition of return system, however, it appears to be delayed developmentally.     

Neuropsychological characteristics of children with the 22q11 Deletion Syndrome: a descriptive analysis.

Previous reports of cognitive functioning in children with the 22q11 Deletion Syndrome have reported marked variability in IQ and achievement subtest scores. Studies have begun to explore neuropsychological function in 22q11 DS however results are inconsistent and the profile incomplete. We assessed 40 children ages 5-12 with 22q11 DS. Consistent with past results, visual-spatial memory was significantly lower than verbal memory. Differentially lowered scores were found only in visual attention, working memory and motor function. Contrary with some past results quantitative, verbal ability, and visual spatial memory scores were within 1 SD from the standardization sample mean. Motor behavior, not typically discussed with regard to 22q11 DS school-age children, may be critical to incorporate in neurocognitive studies of children with 22q11 DS. Implications of these findings are considered with regard to past results.     

The relationship between speed of information processing and cognitive ability

Speed of information processing as measured by various reaction time and inspection tasks has been shown to correlate with psychometric intelligence, and it has been suggested that general intelligence (g) is determined to some degree by the speed that information is processed. If this is so, then various measures of speed of information processing should correlate substantially with each other, and each should also correlate with a wide range of psychometric tests that load on g. Alternatively, intelligence may be considered to be a multi-faceted complex of partially related abilities with specific abilities being dependent upon specific cognitive processes. If this is the case, it should be possible to discover independent cognitive processes, some of which correlate with one facet or broad ability and some with another. This paper presents three experiments in which the relationship between intellectual ability and four speed of information processing measures was examined. These were rate of memory scanning, rate of retrieval of information from long term memory, speed of stimulus-response mapping and inspection time (IT). Results showed that correlations between IT and most reaction time measures of speed of information processing were low, and that correlations between different versions of IT were negligible. In addition, some cognitive tasks with verbal material (memory scanning rate for digits and Posner letter matching IT) correlated most substantially with Verbal Reasoning whereas non-verbal (two-line) IT consistently correlated with tests loading on g. It was thus suggested that while non-verbal IT may be a measure of a perceptual speed attribute that contributes to mental functioning, other “speed of information processing” parameters may be more specific to a subset of abilities.     

Common and specific cognitive deficits in schizophrenia: relationships to function

The goals of the present study were to assess the interrelationships among tasks from the MATRICS and CNTRACS batteries, to determine the degree to which tasks from each battery capture unique variance in cognitive dysfunction in schizophrenia, and to determine the ability of tasks from each battery to predict functional outcome. Subjects were 104 schizophrenia patients and 132 healthy control subjects recruited as part of the CNTRACS initiative. All subjects completed four CNTRACS tasks and two tasks from the MATRICS battery: Brief Assessment of Cognition in Schizophrenia Symbol Coding and the Hopkins Verbal Learning Test. Functional outcome was also assessed in the schizophrenia subjects. In both the patient and control groups, we found significant intercorrelations between all higher order cognitive tasks (episodic memory, goal maintenance, processing speed, verbal learning) but minimal relationships with the visual task. For almost all tasks, scores were significantly related to measures of functional outcome, with higher associations between CNTRACS tasks and performance-based measures of function and between one of the MATRICS tasks and self-reported functioning, relative to the other functioning measures. After regressing out variance shared by other tasks, we continued to observe group differences in performance among task residuals, particularly for measures of episodic memory from both batteries, although these residuals did not correlate as robustly with functional outcome as raw test scores. These findings suggest that there exists both shared and specific variance across cognitive tasks related to cognitive and functional impairments in schizophrenia and that measures derived from cognitive neuroscience can predict functional capacity and status in schizophrenia.     

Cognitive functioning in healthy older adults aged 64-81: a cohort study into the effects of age, sex, and education

The objective of this study was to determine a possible differential effect of age, education, and sex on cognitive speed, verbal memory, executive functioning, and verbal fluency in healthy older adults. A group of 578 healthy participants in the age range of 64-81 was recruited from a large population study of healthy adults (Maastricht Aging Study). Even in healthy individuals in this restricted age range, there is a clear, age-related decrease in performance on executive functioning, verbal fluency, verbal memory, and cognitive speed tasks. The capacity to inhibit information is affected most. Education had a substantial effect on cognitive functioning: participants with a middle or high level of education performed better on cognitive tests than did participants with a low level of education. Women performed better than men on verbal memory tasks. Therefore, education and sex must be taken into account when examining an older individual's cognitive performance.     

The effects of concurrent verbal and visual tasks on category learning

Current theories of category learning posit separate verbal and nonverbal learning systems. Past research suggests that the verbal system relies on verbal working memory and executive functioning and learns rule-defined categories; the nonverbal system does not rely on verbal working memory and learns non-rule-defined categories (E. M. Waldron & F. G. Ashby, 2001; D. Zeithamova & W. T. Maddox, 2006). However, relatively little research has explored the importance of visual working memory or visual processing for either system. The authors investigated the role of working memory (Experiment 1a and 1b), visual processing (Experiment 2), and executive functioning for each system, using a concurrent task methodology. It was found that visual tasks with high executive functioning demands and verbal tasks with high or low executive demands disrupted rule-defined learning, whereas any visual task, regardless of executive functioning demand, disrupted non-rule-defined learning. Taken together, these results confirm the importance of verbal working memory and executive functioning for the verbal system and provide new evidence for the importance of visual processing for the nonverbal system. These results help to clarify understanding of the nonverbal system and have implications for multiple systems theories of category learning (F. G. Ashby, L. A. Alfonso-Reese, A. U. Turken, & E. M. Waldron, 1998).     

The extent of working memory deficits associated with Williams syndrome: exploration of verbal and spatial domains and executively controlled processes

The present study investigated verbal and spatial working memory (WM) functioning in individuals with the neuro-developmental disorder Williams syndrome (WS) using WM component tasks. While there is strong evidence of WM impairments in WS, previous research has focused on short-term memory and has neglected assessment of executive components of WM. There is a particular lack of consensus concerning the profile of verbal WM functioning in WS. Here, WS participants were compared to typically developing participants matched for (1) verbal ability and (2) spatial ability (N = 14 in each of the 3 groups). Individuals with WS were impaired on verbal WM tasks, both those involving short-term maintenance of information and executive manipulation, in comparison to verbal-matched controls. Surprisingly, individuals with WS were not impaired on a spatial task assessing short-term maintenance of information in memory (remembering spatial locations) compared to spatial-matched controls. They were, however, impaired on a spatial executive WM task requiring the manipulation of spatial information in memory. The present study suggests that individuals with WS show WM impairments that extend to both verbal and spatial domains, although spatial deficits are selective to executive aspects of WM function.     

Differences in the neurocognitive profiles of professional and semi-professional male South African rugby union players

This study investigated possible cognitive functioning profile differences between professional and semi-professional rugby players. Seventy-nine male rugby union players (professional = 55, semi-professional = 24; age range = 19–37 years) participated in the study. The players completed a battery of neuropsychological functioning tests covering the following domains: memory tasks, attention and behavioural tasks, sensory-motor tasks, executive functioning tasks, verbal tasks, and emotion identification tasks. Results following Fisher’s exact test comparisons revealed no significant group differences in the cognitive functioning profiles.     

Effects of proactive interference on non-verbal working memory

Working memory (WM) is a cognitive system responsible for actively maintaining and processing relevant information and is central to successful cognition. A process critical to WM is the resolution of proactive interference (PI), which involves suppressing memory intrusions from prior memories that are no longer relevant. Most studies that have examined resistance to PI in a process-pure fashion used verbal material. By contrast, studies using non-verbal material are scarce, and it remains unclear whether the effect of PI is domain-general or whether it applies solely to the verbal domain. The aim of the present study was to examine the effect of PI in visual WM using both objects with high and low nameability. Using a Directed-Forgetting paradigm, we varied discriminability between WM items on two dimensions, one verbal (high-nameability vs. low-nameability objects) and one perceptual (colored vs. gray objects). As in previous studies using verbal material, effects of PI were found with object stimuli, even after controlling for verbal labels being used (i.e., low-nameability condition). We also found that the addition of distinctive features (color, verbal label) increased performance in rejecting intrusion probes, most likely through an increase in discriminability between content–context bindings in WM.     

Social perception and WAIS-IV Performance in adolescents and adults diagnosed with Asperger's Syndrome and Autism

Previous research using the Wechsler scales has identified areas of cognitive weaknesses in children, adolescents, and adults diagnosed with Autism or Asperger's syndrome. The current study evaluates cognitive functioning in adolescents and adults diagnosed with Autism or Asperger's syndrome using the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) and the Social Perception subtest from the Advanced Clinical Solutions. Deficits in social perception, verbal comprehension, and processing speed were found in the Autism sample. Additionally, they exhibited inconsistent performance on auditory working memory and perceptual reasoning tasks. The Asperger's syndrome group had better overall cognitive skills than the Autism group, but compared with controls, they had weaknesses in processing speed, social perception, and components of auditory working memory. Both groups had relatively low scores on the WAIS-IV Comprehension subtest compared with the other verbal comprehension subtests. Clinical application and utility of the WAIS-IV and Social Perception in Autism Spectrum Disorders are discussed.