Karen Lidzba

LI-tool: A new toolbox to assess lateralization in functional MR-data

A lateralization index (LI) is commonly computed to describe the asymmetry of activation as detectable by various functional imaging techniques, particularly functional magnetic resonance imaging (fMRI). In this article, we examine and compare different approaches that have been used in the past. For illustration purposes, 100 synthetic datasets and real fMRI-data from 12 subjects were evaluated. As shown before, the calculation of a lateralization index suffers from a number of drawbacks, namely vulnerability to statistical outliers, data sparsity, thresholding effects and lack of taking into account regional variability of activation. Optional processing steps investigated here seem to increase reliability of the such-calculated indices. To allow a more standardized, reproducible and accessible evaluation of laterality effects, current and new approaches have been implemented in a versatile toolbox running within the spm2 or spm5 software environment.

Right-Hemispheric Organization of Language Following Early Left-Sided Brain Lesions: Functional MRI Topography

Left-hemispheric (LH) brain lesions acquired early in life can induce language organization in the undamaged right hemisphere (RH). This study addresses the anatomical correlates of language processing in the RH of such individuals. Five hemiparetic patients with left periventricular brain lesions of pre- and perinatal origin were included, in whom fMRI during a word generation task had yielded predominantly RH activation; five age- and sex-matched healthy right-handers served as controls. The patterns of activation in the RH of patients showed a striking similarity with the LH patterns of the normal controls, and voxel-wise comparison failed to detect significant differences. This demonstrates that in patients with early LH damage, RH recruitment for language occurs in brain areas homotopic to the LH regions involved in language processing under normal circumstances.

Strengthening of Laterality of Verbal and Visuospatial Functions During Childhood and Adolescence

Cognitive functions in the childs brain develop in the context of complex adaptive processes, determined by genetic and environmental factors. Little is known about the cerebral representation of cognitive functions during development. In particular, knowledge about the development of right hemispheric (RH) functions is scarce. Considering the dynamics of brain development, localization and lateralization of cognitive functions must be expected to change with age. Twenty healthy subjects (8.6–20.5 years) were examined with fMRI and neuropsychological tests. All participants completed two fMRI tasks known to activate left hemispheric (LH) regions (language tasks) and two tasks known to involve predominantly RH areas (visual search tasks). A laterality index (LI) was computed to determine the asymmetry of activation. Group analysis revealed unilateral activation of the LH language circuitry during language tasks while visual search tasks induced a more widespread RH activation pattern in frontal, superior temporal, and occipital areas. Laterality of language increased between the ages of 8–20 in frontal (r = 0.392, P = 0.049) and temporal (r = 0.387, P = 0.051) areas. The asymmetry of visual search functions increased in frontal (r = −0.525, P = 0.009) and parietal (r = −0.439, P = 0.027) regions. A positive correlation was found between Verbal‐IQ and the LI during a language task (r = 0.585, P = 0.028), while visuospatial skills correlated with LIs of visual search (r = −0.621, P = 0.018). To summarize, cognitive development is accompanied by changes in the functional representation of neuronal circuitries, with a strengthening of lateralization not only for LH but also for RH functions. Our data show that age and performance, independently, account for the increases of laterality with age. Hum Brain Mapp, 2009.

Increases in Language Lateralization in Normal Children as Observed Using Magnetoencephalography.

Previous functional magnetic resonance imaging (fMRI) studies investigating hemispheric dominance for language have shown that hemispheric specialization increases with age. We employed magnetoencephalography (MEG) to investigate these effects as a function of normal development. In sum, 22 healthy children aged 7-16 years were investigated using two language tasks: a verb-generation (VG) task and a vowel-identification (VI) task. Significant hemispheric differences were found for both tasks in cerebral language areas using oscillatory MEG spectral analyses, confirming the MEGs ability to detect hemispheric specialization for language in children. Additionally, a significant increase of this lateralization as a function of age was observed for both tasks. As performance in the VI task showed no correlation with age, this increase seems to be unrelated to performance. These results confirm an increase in hemispheric specialization as a function of normal brain maturation.

Language comprehension vs. language production: age effects on fMRI activation.

Normal language acquisition is a process that unfolds with amazing speed primarily in the first years of life. However, the refinement of linguistic proficiency is an ongoing process, extending well into childhood and adolescence. An increase in lateralization and a more focussed productive language network have been suggested to be the neural correlates of this process. However, the processes underlying the refinement of language comprehension are less clear. Using a language comprehension (Beep Stories) and a language production (Vowel Identification) task in fMRI, we studied language representation and lateralization in 36 children, adolescents, and young adults (age 6-24 years). For the language comprehension network, we found a more focal activation with age in the bilateral superior temporal gyri. No significant increase of lateralization with age could be observed, so the neural basis of language comprehension as assessed with the Beep Stories task seems to be established in a bilateral network by late childhood. For the productive network, however, we could confirm an increase with age both in focus and lateralization. Only in the language comprehension task did verbal IQ correlate with lateralization, with higher verbal IQ being associated with more right-hemispheric involvement. In some subjects (24%), language comprehension and language production were lateralized to opposite hemispheres.

An fMRI task battery for assessing hemispheric language dominance in children.

Hemispheric dominance for language is an important issue in functional neuroimaging, particularly driven by efforts to overcome the need for the invasive Wada test, which is all the more pressing in children. Here, we aimed at developing new paradigms for functional magnetic resonance imaging (fMRI) for assessment of language dominance that can be used in younger children and allow for performance monitoring. Two new tasks (letter and animal task) were developed and compared to two reference tasks (synonyms and verb generation task) from the literature. Overall, 23 healthy children participated (13 boys, 10 girls, 10.2 +/- 2.5 years, range 6.1-15.3 years). Analysis was done using statistical nonparametrical mapping (SnPM2) on SPM2. Both reference tasks show activation in a number of left-frontal brain regions. The letter task induced a very localized activation in the left hemispheres Brocas region, while not activating other frontal brain regions. Lateralization (as assessed in different anatomically and functionally defined regions) was consistent and strong. The animal task failed to activate frontal brain regions and was not suitable for assessing language dominance in children in this form. We conclude that while both reference tasks are useful for determining language dominance, they coactivate a number of task-related frontal areas not directly involved in language processing. Additionally, one task is not applicable in young children while the other does not allow performance monitoring. The letter task allows to selectively activate language areas in the dominant hemisphere and is applicable even in the very lowest age group amenable to fMRI investigations while still allowing performance monitoring. It may thus be a useful tool in assessing normal and pathological language organization.

Reorganization of the Cerebro-Cerebellar Network of Language Production in Patients with Congenital Left-Hemispheric Brain Lesions.

Patients with congenital lesions of the left cerebral hemisphere may reorganize language functions into the right hemisphere. In these patients, language production is represented homotopically to the left-hemispheric language areas. We studied cerebellar activation in five patients with congenital lesions of the left cerebral hemisphere to assess if the language network is reorganized completely in these patients, i.e. including also cerebellar language functions. As compared to a group of controls matched for age, sex, and verbal IQ, the patients recruited an area not in the right but in the left cerebellar hemisphere. The extent of laterality of the cerebellar activation correlated significantly with the laterality of the frontal activation. We suggest that the developing brain reacts to early focal lesions in the left hemisphere with a mirror-image organization of the entire cerebro-cerebellar network engaged in speech production.

Comprehensive language mapping in children, using functional magnetic resonance imaging: what's missing counts.

Noninvasive language mapping is a frequently used application of functional magnetic resonance imaging. The examination of children, however, poses both practical and technical challenges. To this effect, we have developed two new paradigms mainly requiring passive listening to stories from which several key words were removed. Results were compared with a standard active verb-generation task, particularly with regard to hemispheric dominance in frontal brain areas. Fifteen healthy children (seven boys, eight girls, 6–14 years) were scanned. Distinct frontal activation was seen in our new tasks, which was stronger when the tasks were analyzed specifically with regard to the missing words. This confirms the hypothesis that the removal of these words is the key in inducing frontal activation. Frontal lateralization was consistent and strong in all three paradigms. Additionally, receptive language areas are also mapped by our new tasks. We conclude that our two new, child-friendly functional magnetic resonance imaging paradigms are useful in determining hemispheric dominance for language in children too young or too impaired to execute an active task. They also allow robust mapping of receptive language areas.

Postnatal Human Cytomegalovirus Infection in Preterm Infants Has Long-Term Neuropsychological Sequelae

OBJECTIVE To evaluate whether an early postnatal infection poses a long-term risk for neuropsychological impairment to neonates born very prematurely. STUDY DESIGN Adolescents born very preterm (n = 42, 11.6-16.2 years, mean = 13.9; 15 girls; 19 with and 23 without an early postnatal human cytomegalovirus [CMV] infection) and typically developing, term born controls (n = 24, 11.3-16.6 years, mean = 13.6; 12 girls) were neuropsychologically assessed with the German version of the Wechsler Intelligence Scale and the Developmental Test for Visual Perception. RESULTS As expected, the full cohort of adolescents born preterm had significantly lower scores than term born controls on IQ (preterm: mean [SD] = 98.43 [14.83], control: 110.00 [8.10], P = .015) and on visuoperceptive abilities (95.64 [12.87] vs 106.24 [9.95], P = .016). Furthermore, adolescents born preterm with early postnatal CMV infection scored significantly lower than those without this infection regarding overall cognitive abilities (92.67 [14.71] vs 102.75 [13.67], P = .030), but not visuoperceptive abilities (91.22 [10.88] vs 98.96 [13.45], P > .05). CONCLUSIONS In our small but well-characterized group, our results provide evidence for adverse effects of early postnatal CMV infection on overall cognitive functions in adolescents born preterm. If confirmed, these results support the implementation of preventive measures.

The adverse influence of attention-deficit disorder with or without hyperactivity on cognition in neurofibromatosis type 1.

Aim  A substantial proportion of patients with neurofibromatosis type 1 (NF1) have attention‐deficit disorder with or without hyperactivity (AD[H]D). This study explored the influence of AD(H)D symptoms on the intellectual profile of patients with NF1.