M.P.H. Hendriks

Neuropsychological features of patients with spinocerebellar ataxia (SCA) types 1, 2, 3, and 6.

A subtype-specific impairment of cognitive functions in spinocerebellar ataxia (SCA) patients is still debated. Thirty-two SCA patients (SCA1, 6; SC2, 3; SCA3, 15; SCA6, 8) and 14 matched healthy controls underwent neuropsychological evaluation testing attention, executive functions, episodic and semantic memory, and motor coordination. Severity of ataxia was assessed with the Scale for the Assessment and Rating of Ataxia (SARA), nonataxia symptoms with the Inventory of Non-Ataxia Symptoms. Depressive symptoms were evaluated with the Beck Depression Inventory. The SARA scores of our SCA patients (range 1–19.5) indicated an overall moderate ataxia, most pronounced in SCA6 and SCA1. Mean number of nonataxia symptoms (range 0–2.2) were most distinct in SCA1 and nearly absent in SCA6. SCA1 performed poorer than controls in 33% of all cognitive test parameters, followed by SCA2, SCA3, and SCA6 patients (17%). SCA 1–3 patients presented mainly attentional and executive dysfunctions while semantic and episodic memory functions were preserved. Attentional and executive functions were partly correlated with ataxia severity and fine motor coordination. All patients exhibited mildly depressed mood. Motor and dominant hand functions were more predictive for depressed mood than cognitive measures or overall ataxia. Besides motor impairments in all patients, SCA patients with extracerebellar pathology (SCA 1–3) were characterized by poor frontal attentional and executive dysfunction while mild cognitive impairments in predominantly cerebellar SCA6 patients appeared to reflect mainly cerebellar dysfunction. Regarding the everyday relevance of symptoms, (dominant) motor hand functioning emerged as a marker for the patient’s mood.

Working memory deficits in high-functioning adolescents with autism spectrum disorders: neuropsychological and neuroimaging correlates

Working memory is a temporary storage system under attentional control. It is believed to play a central role in online processing of complex cognitive information and may also play a role in social cognition and interpersonal interactions. Adolescents with a disorder on the autism spectrum display problems in precisely these domains. Social impairments, communication difficulties, and repetitive interests and activities are core domains of autism spectrum disorders (ASD), and executive function problems are often seen throughout the spectrum. As the main cognitive theories of ASD, including the theory of mind deficit hypotheses, weak central coherence account, and the executive dysfunction theory, still fail to explain the broad spectrum of symptoms, a new perspective on the etiology of ASD is needed. Deficits in working memory are central to many theories of psychopathology, and are generally linked to frontal-lobe dysfunction. This article will review neuropsychological and (functional) brain imaging studies on working memory in adolescents with ASD. Although still disputed, it is concluded that within the working memory system specific problems of spatial working memory are often seen in adolescents with ASD. These problems increase when information is more complex and greater demands on working memory are made. Neuroimaging studies indicate a more global working memory processing or connectivity deficiency, rather than a focused deficit in the prefrontal cortex. More research is needed to relate these working memory difficulties and neuroimaging results in ASD to the behavioral difficulties as seen in individuals with a disorder on the autism spectrum.

Working memory performance and executive function behaviors in young children with SLI

The present study compared the performances of young children with specific language impairment (SLI) to that of typically developing (TD) children on cognitive measures of working memory (WM) and behavioral ratings of executive functions (EF). The Automated Working Memory Assessment was administered to 58 children with SLI and 58 TD children aged 4 and 5 years. Additionally, parents completed the Behavior Rating Inventory of Executive Function - Preschool Version. The results showed the SLI group to perform significantly worse than the TD group on both cognitive and behavioral measures of WM. The deficits in WM performance were not restricted to the verbal domain, but also affected visuospatial WM. The deficits in EF behaviors included problems with inhibition, shifting, emotional control, and planning/organization. The patterns of associations between WM performance and EF behaviors differed for the SLI versus TD groups. WM performance significantly discriminated between young children with SLI and TD, with 89% of the children classified correctly. The data indicate domain general impairments in WM and problems in EF behaviors in young children with SLI. Attention should thus be paid to WM - both verbal and visuospatial - and EF in clinical practice. Implications for assessment and remediation were discussed.

Relationships between epilepsy-related factors and memory impairment.

Objectives:  In this study, we will explore the effect of epilepsy‐related factors such as: ‘type of epilepsy, ‘site and side of focus localisation’ and ‘age at onset’, as well as four seizure‐related factors: ‘years with continuing seizures’, ‘seizure type’ and ‘seizure frequency’, and the treatment factor ‘adverse effects of the medication’, on memory impairment. Additionally, we explored whether these epilepsy factors are related to different aspects of memory, i.e. short‐term recall vs long‐term recall, learning, and verbal memory vs non‐verbal memory.

Memory Complaints in Medically Refractory Epilepsy: Relationship to Epilepsy-Related Factors

This study reports the results of a multicenter study on memory complaints in 252 patients with epilepsy who presented with subjective complaints about memory problems in daily life. Memory complaints were measured with a standardized memory questionnaire (GKLE). The main purpose was to analyze the type of memory complaints and to examine the relationship between subjective complaints and several epilepsy-related factors. These include seizure type, lateralization and location of the focus, etiology, duration, age at onset, and antiepileptic medication. As expected patients experienced significantly more memory complaints. In particular, patients of older age and higher intelligence level complained more about their memory functioning. Although the clinical significance is marginal, neuroticism showed a significant relationship to the total complaint score. The total amount of subjective complaints is not related to the localization or lateralization of the epileptic disturbances. Patients with a longer duration of epilepsy complained significantly more about memory problems, especially about retrieving information from memory. All other epilepsy-related factors showed no relationship to memory complaints.

Visuospatial working memory in specific language impairment: A meta-analysis

We conducted a meta-analysis of the data from studies comparing visuospatial working memory (WM) in children with specific language impairment (SLI) and typically developing (TD) children. The effect sizes of 21 studies (including 32 visuospatial storage tasks and 9 visuospatial central executive (CE) tasks) were identified via computerized database searches and the reference sections of the identified studies. Meta-analyses and moderator analyses were conducted to examine the magnitude of the differences in visuospatial storage and CE, and their relation to the inclusion criteria used for SLI and the age of the children. The results showed significant effect sizes for visuospatial storage (d=0.49) and visuospatial CE (d=0.63), indicating deficits in both components of visuospatial WM in children with SLI. The moderator analyses showed that greater impairment in visuospatial storage was associated with more pervasive language impairment, whereas age was not significant associated with visuospatial WM. The finding of deficits in visuospatial WM suggests domain-general impairments in children with SLI. It raises questions about the language-specificity of a diagnosis of SLI. Careful attention should thus be paid to both verbal and visuospatial WM in clinical practice, and especially in those children with pervasive language impairments.

Long-term effects of temporal lobectomy on intelligence.

Objective: To characterize the long-term effects of anterior temporal resection on intelligence. Methods: Twenty-eight left temporal lobectomy (LTL) and 43 right temporal lobectomy (RTL) patients were followed at standard time points for at least 6 years after surgery. Results: The average gain 6 years after operation was 3.6 Verbal IQ (VIQ) points and 10.3 Performance IQ (PIQ) points in LTL patients and 2.9 VIQ points and 7.7 PIQ points in RTL patients. A seizure-free outcome did not influence the increase in IQ, nor was the extent of resection related to IQ scores at the 6-year follow-up. Patients with exclusively mesial temporal sclerosis did not perform as well as patients with other pathologies, both before and after surgery. Major predictors of improved performance at 6 years were initial higher level of performance and lower age at surgery. Much of the observed improvement may be related to retest effects. Conclusions: The effects of epilepsy surgery on intelligence in the long term are limited. The largest gain in VIQ is seen from 2 to 6 years after surgery.

Altered neurotransmitter metabolism in adolescents with high-functioning autism

Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy (1H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few 1H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using 1H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.

Interactions between working memory and language in young children with specific language impairment (SLI)

The underlying structure of working memory (WM) in young children with and without specific language impairment (SLI) was examined. The associations between the components of WM and the language abilities of young children with SLI were then analyzed. The Automated Working Memory Assessment and four linguistic tasks were administered to 58 children with SLI and 58 children without SLI, aged 4–5 years. The WM of the children was best represented by a model with four separate but interacting components of verbal storage, visuospatial storage, verbal central executive (CE), and visuospatial CE. The associations between the four components of WM did not differ significantly for the two groups of children. However, the individual components of WM showed varying associations with the language abilities of the children with SLI. The verbal CE component of WM was moderately to strongly associated with all the language abilities in children with SLI: receptive vocabulary, expressive vocabulary, verbal comprehension, and syntactic development. These results show verbal CE to be involved in a wide range of linguistic skills; the limited ability of young children with SLI to simultaneously store and process verbal information may constrain their acquisition of linguistic skills. Attention should thus be paid to the language problems of children with SLI, but also to the WM impairments that can contribute to their language problems.

Visual memory after epilepsy surgery in children: A standardized regression-based analysis of group and individual outcomes

Visual memory is vulnerable to epilepsy surgery in adults, but studies in children suggest no change or small improvements. We investigated visual memory after epilepsy surgery, both group-wise and in individual children, using two techniques to assess change: 1) repeated measures analysis of variance (ANOVA) and 2) an empirically based technique for detecting cognitive change [standardized regression-based (SRB) analysis]. A prospective cohort consisting of 21 children completed comprehensive assessments of memory both before surgery (T0) and 6 (T1), 12 (T2), and 24 months (T3) after surgery. For each patient, two age- and gender-matched controls were assessed with the same tests at the same intervals. Repeated measures ANOVA replicated the results of previous studies reporting no change or minor improvements after surgery. However, group analysis of SRB results eliminated virtually all improvements, indicating that the ANOVA results were confounded by practice effects. Standardized regression-based group results showed that in fact patients scored lower after surgery than would be predicted based on their presurgical performance. Analysis of individual SRB results showed that per visual memory measure, an average of 18% of patients obtained a significantly negative SRB score, whereas, on average, only 2% obtained a significantly positive SRB score. At T3, the number of significantly negative SRB scores outweighed the number of significantly positive SRB scores in 62% of patients. There were no clear associations of clinical variables (including side and site of surgery and postsurgical seizure freedom) with memory outcome. The present analysis revealed that given their individual presurgical functioning, many children obtained disappointing results on some visual memory tests after epilepsy surgery. Comparison of the SRB analysis with ANOVA results emphasizes the importance of empirically based techniques for detecting cognitive effects of epilepsy surgery in childhood.