Cognitive and White Matter Tract Differences in MS and Diffuse Neuropsychiatric Systemic Lupus Erythematosus.

BACKGROUND AND PURPOSE: Multiple sclerosis and neuropsychiatric systemic lupus erythematosus are autoimmune diseases with similar CNS inflammatory and neurodegenerative characteristics. Our aim was to investigate white matter tract changes and their association with cognitive function in patients with MS and those with neuropsychiatric systemic lupus erythematosus compared with healthy controls by using diffusion tensor imaging. MATERIALS AND METHODS: Thirty patients with relapsing-remitting MS and 23 patients with neuropsychiatric systemic lupus erythematosus matched for disease severity and duration and 43 healthy controls were scanned with 3T MR imaging. The DTI was postprocessed, corrected for lesions, and analyzed with tract-based spatial statistics. Cognitive assessment included examination of processing speed; visual, auditory/verbal, and visual-spatial memory; and sustained attention and executive function. Differences were considered significant at P < .05. RESULTS: Tract-based spatial statistics analysis revealed significantly decreased fractional anisotropy and increased mean diffusivity in patients with MS compared with healthy controls, decreased fractional anisotropy in patients with MS compared with those with neuropsychiatric systemic lupus erythematosus, and an increased mean diffusivity in patients with neuropsychiatric systemic lupus erythematosus compared with healthy controls. Patients with MS showed decreased fractional anisotropy throughout central WM pathways, including the corpus callosum and the inferior longitudinal and fronto-occipital fasciculi compared with those with neuropsychiatric systemic lupus erythematosus. Altered cognitive scores in patients with MS were significantly associated with decreased fractional anisotropy and increased mean diffusivity in all examined domains, while in patients with diffuse neuropsychiatric systemic lupus erythematosus, only decreased fractional anisotropy in the superior WM pathways showed significant association with executive function. CONCLUSIONS: Patients with MS and neuropsychiatric systemic lupus erythematosus showed widespread WM tract alterations outside overt lesions, though more severe changes were identified in patients with MS. The WM tract changes were associated with cognitive dysfunction in all explored domains only in patients with MS.

Multimodal imaging in systemic lupus erythematosus patients with diffuse neuropsychiatric involvement.

OBJECTIVES: The objective of this paper is to investigate conventional and nonconventional brain magnetic resonance imaging (MRI) findings in systemic lupus erythematosus (SLE) patients with diffuse neuropsychiatric involvement (dNPSLE) compared to healthy controls (HCs). METHODS: Twenty-six (26) SLE patients with one or more diffuse NP syndromes related to the central nervous system (CNS) (dNPSLE) and 36 age- and sex-matched HCs were scanned on a 3T MRI using a multimodal imaging approach. Univariate and multivariate analyses were used to determine MRI-specific measure differences between dNPSLE and HCs for lesion burden, tissue-specific atrophy, magnetization transfer ratio (MTR) and diffusion-tensor imaging (DTI) outcomes. RESULTS: In univariate analyses, dNPSLE patients showed significantly increased T1 lesion number (p = .001) and T1-lesion volume (LV, p = .008) compared to HCs. dNPSLE patients showed decreased whole brain volume (p < .0001), gray matter volume (p < .0001), cortical volume (p < .0001) and increased lateral ventricle volume (p = .004) compared to HCs. dNPSLE patients had increased axial diffusivity (AD) of NAWM (p = .008) and NA brain tissue (p = .017) compared to HCs. In the multivariate regression analysis, decreased cortical volume was associated with SLE (R (2) = 0.59, p < .0001). CONCLUSIONS: This study shows that cortical and central atrophy are associated with SLE patients with diffuse CNS syndromes. Microscopic tissue injury in the NAWM on AD DTI measures in SLE patients indicates a predominant reduction of axonal density.

Neuropsychological impairment in systemic lupus erythematosus: a comparison with multiple sclerosis.

In this manuscript, we review literature describing the neuropsychological and brain imaging characteristics of systemic lupus erythematosus (SLE) patients. The findings are compared and contrasted with multiple sclerosis (MS) studies, revealing similarities and differences of interest to clinicians and researchers. While cognitive impairment is somewhat less common in SLE than MS, the diseases share a similar cognitive profile with deficits most prominent on tests emphasizing the speed of information processing, working memory, and visual/spatial learning, and memory. In early or more mildly affected patients, diffuse white matter damage, which may not be apparent on conventional brain imaging, plays a major role in clinical presentation and cognitive testing. The causes of white matter damage are very different, however, and in later stages of the disease MS and SLE appear to give rise to different forms of cerebral pathology. MS may be characterized by increasing brain atrophy affecting especially the cortical and deep gray matter, at least after conversion to secondary progressive course. There is less evidence for neurodegenerative changes in SLE, but patients are increasingly at risk for cerebrovascular disease. We conclude by offering some suggestions for future clinical and imaging research.

Sex-related differences in event-related potentials, face recognition, and facial affect processing in prepubertal children.

Thirty-five prepubertal children, 17 boys and 18 girls, between the ages of 8 and 11 years, were studied to examine electrophysiological and cognitive sex differences during a face-recognition-memory (FRM) task and a facial-affect-identification task (FAIT). All participants were prepubertal, as determined by J. M. Tanner's (1962) staging and endocrine evaluation. Sex-dependent event-related potential (ERP) amplitude asymmetries were found during FRM. Boys displayed greater right versus left ERP amplitude to auditory tone probes during the task, whereas girls displayed the opposite pattern. In addition, positive correlations were obtained between ERP amplitude during FRM and FAIT accuracy scores for boys, but not for girls. Results suggest that girls and boys may use different neuronal systems in the processing of faces and facial affect. Findings are consistent with developmental theories regarding sex differences in visuospatial processing.

Stimulus modality and Go/NoGo effects on P3 during parallel visual and auditory continuous performance tasks.

Task and modality effects on P3 latency, amplitude, and scalp topography were studied during parallel versions of visual (VCPT) and auditory (ACPT) continuous performance tasks using a Go/NoGo paradigm (A-X CPT). Both the ACPT and VCPT incorporated five conditions including Go and NoGo stimulus sequences as well as three other nontarget conditions. The goal was to evaluate the functional significance and modality specificity of the P300 response and the NoGo P3. Analyses were performed using both raw and normalized data to make comparisons across modalities. For both modalities, the Target X (Go) and three nontarget conditions elicited maximum P3 amplitudes over the posterior scalp sites and qualified as classical P300 responses. The NoGo condition was associated with an increase in central-frontal amplitude compared to the Target X condition. The scalp topography of the P300/P3 for Go and NoGo conditions, as well as all other conditions, was the same for both modalities, supporting the modality independent nature of both P300 and the NoGo P3. Min-Max normalization of P3 amplitudes did not change the condition-topography relationships.

An electrophysiological study of infants' sensitivity to the sound patterns of English speech.

The study explores 10- to 11-month-old infants' sensitivity to the phonological characteristics of their native language. Event-related potentials (ERPs) were obtained for tones that were superimposed on two versions of a story: an Unmodified version containing normal English function morphemes, and a Modified version in which the prosodic and segmental properties of a subset of function morphemes were changed to make them atypical. The 11-month-olds exhibited significantly lower amplitude ERPs to the tones during the Modified story than to the Unmodified story, whereas the 10-month-olds showed no differences. These results suggest that the 11-month-olds discriminated the two versions of the story based on their representations of the phonological properties of English. Further, the tone-probe ERP method can successfully be used to study the development of speech perception in the pre-linguistic infant.

Functional neuroimaging of attention in the auditory modality.

Previous functional neuroimaging studies of attention have emphasized the visual modality. We developed an auditory version of the continuous performance test (CPT) that included simple, focused and divided attention conditions. Positron emission tomographic (PET) scans were acquired during CPT performance in normal young adults and then submitted to statistical parametric mapping. Simple attention brought about a large region of activation involving the anterior cingulate gyrus and the right anterior/mesial frontal lobe. Focused and divided attention CPT conditions were compared but there were few significant differences. The findings are consistent with activation of an anterior attention network during auditory attention, without involvement of posterior attention structures which are more likely to vary in accordance with sensory modality.

Neurophysiological studies of human cognitive development in premature infants: an approach to the study of maturational brain processes.

In normal cerebral development, language function typically becomes lateralized in the left hemisphere in most individuals. It is theorized that disturbances in the development of this cerebral asymmetry may result in language dysfunction such as dyslexia and dysphasia. Recently, it has been reported that language disturbances occur in many children who were born prematurely and who have suffered insults such as asphyxia and hyperbilirubinemia. Premature infants have also been shown to have a high incidence of abnormalities associated with auditory reception. Thus, it is possible that perinatal insults could lead to disturbances in the development of normal central nervous system (CNS) functional organization which result in later learning disabilities. The extent to which such learning impairments are related to nervous system development and to the subsequent limitations placed by neonatal insults upon cognitive capacities, is unknown. The purpose of this study was to examine the relationships among neurophysiological indices of CNS function, language development, and general infant competence over the first two years of life in order to provide information concerning the ontogenesis of higher cognitive functioning in both preterm and full term infants. In this report we will present an overview of the relevant issues in the area and focus on some of the neurophysiological data obtained to date. The approach discussed might prove useful in the study of any group of infants at risk for cognitive and/or developmental disorders related to a variety of perinatal insults.

Prenatal lead exposure and its potential significance for developmental disabilities: a preliminary study of umbilical cord blood lead levels.

It has been reported that between 1976-1980 the mean blood lead level in American preschool children was 16 micrograms/dl. The Centers for Disease Control (CDC) recently set a blood level of 25 micrograms/dl as the highest acceptable level for children. However, current research findings have provided evidence that detrimental effects on development can occur when lead levels are below this acceptable value. In particular, recent work has shown a relationship between early (prenatal) exposure to lead and delayed cognitive development. Because the developing fetus is particularly vulnerable to insult, it is of critical importance to obtain information about the developmental effects of prenatal exposure to lead and about those factors that may influence this exposure. This report presents initial findings of an ongoing investigation pertaining to issues surrounding early lead exposure. To date umbilical cord blood samples have been measured in 802 infants born at Children's Hospital of Buffalo between November 1987 and April 1988. These infants' residence span approximately 50 townships with most residing in Buffalo proper. Approximately 60 percent of the infants had measurable cord blood lead levels in the range of 4 to 20 micrograms/dl.

Auditory event-related potentials in waking infants and adults: a developmental perspective.

Auditory event-related potentials (AERPs) were recorded in waking 1 month olds, 3 month olds, 6 month olds and adults in order to study the morphology and development of the wave form in the waking subject. Previous data were generally obtained in sleeping or drowsy infants. The findings indicated that there were 3 quantitative changes in the AERP over the first 6 months of life in waking infants: an increase in the latency of peaks, an increase in peak amplitude, and a decrease in intersubject variability. Adult peak latencies were generally shorter than those for 3 month olds and 6 month olds. Further, latencies of earlier AERP peaks for 1 and 6 month olds, in the present study, were comparable to those reported in previous investigations with sleeping infants. However, latencies of later AERP peaks differed from those of previous reports and were closer to those reported for waking adults. With respect to the amplitude, the 6 month olds, in general, had the highest amplitudes, the 1 month olds the lowest, and the 3 month olds and adults fell in between the two groups. Some differences were present between early and late components. The findings of this study are significant in that the AERPs were quantitatively different from those reported in earlier work with sleeping or drowsy infants. If cognitive and perceptual development is to be studied, it is necessary to obtain data on waking subjects. The data presented in this report are consistent with behavioral studies of biobehavioral shifts that are associated with changes in responsivity of the organism to stimuli during the first 6 months of life.

Central nervous system effects of antiasthma medication--an EEG study.

The relationship between electroencephalographic (EEG) abnormalities (in particular paroxysmal activity) and theophylline alone or in combination with corticosteroids and/or ephedrine was examined in 161 adult and 93 pediatric patients. For each patient, total theophylline dosage was calculated and a theophylline blood level was obtained at the time of EEG recording. The major findings indicated: The presence of EEG paroxysmal activity in a greater percentage of the population studied than that which has been reported in a group of nonhospitalized individuals of similar age in the general population. There is a greater probability of EEG paroxysmal activity among patients with higher theophylline blood levels or total dosages than among those with lower blood levels or total dosages. There is an increase in EEG abnormalities with the addition of ephedrine. There is a possible protective effect of steroids against theophylline-related central nervous system disturbances.

Evoked potentials to auditory probes as indices of cerebral specialization of function--replication and extension.

This study was an attempt to replicate findings from previous work in our laboratory as well as to study the relationship between vertex-referenced and linked mastoid-referenced responses under conditions purported to produce differential hemispheric activation. Auditory evoked potentials were recorded between T4-Cz, T3-Cz, T4-A1A2, and T3-A1A2 to task-irrelevant tone pips superimposed on a baseline condition and on two experimental conditions (verbal and music) hypothesized to differentially activate areas of the left and right cerebral hemispheres. Significant AEP amplitude asymmetries were obtained as a function of the ongoing tasks, replicating our previous findings. Higher amplitude AEPs were recorded from temporal-to-vertex leads from the hemisphere thought to be most involved in the ongoing task. In addition, temporal-linked mastoids placements showed an effect opposite to that seen for the vertex-referenced leads with lower amplitude AEPs occurring from the hemisphere purported to be most activated by the task. Mastoid-referenced placements were also less sensitive to task effects than vertex-referenced placements.

Auditory evoked potentials as probes of hemispheric differences in cognitive processing.

The amplitude of auditory evoked potentials recorded from the cerebral hemispheres to pairs of task-irrelevant tones was related to differential hemispheric engagement in ongoing cognitive activity (for example, verbal versus musical). The hemisphere hypothesized to be most engaged in the ongoing cognitive task, as compared to the unengaged hemisphere, produced a greater potential difference between the temporal and reference electrode to the second of the tone pairs. These findings are related to "fast habituation" and "recovery cycle.".