Microstructural integrity of the corpus callosum linked with neuropsychological performance in adolescents

Background: Diffusion tensor imaging (DTI) has revealed microstructural aspects of adolescent brain development, the cognitive correlates of which remain relatively uncharacterized. Methods: DTI was used to assess white matter microstructure in 18 typically developing adolescents (ages 16–18). Fractional anisotropy (FA) and mean diffusion (MD) were evaluated within the splenium and body of the corpus callosum in relation to cognitive performance. Results: Visuospatial construction abilities were associated with white matter integrity in both the splenium and body of the corpus callosum, while only splenium integrity was associated with language and psychomotor function. Conclusion: Results suggest that, for typically developing adolescents, white matter coherence positively relates to visuospatial, psychomotor, and language skills. These findings may have implications for the cognitive functioning of clinical populations in which typical white matter development is altered.     

A combined fMRI and DTI examination of functional language lateralization and arcuate fasciculus structure: Effects of degree versus direction of hand preference

The present study examined the relationship between hand preference degree and direction, functional language lateralization in Broca’s and Wernicke’s areas, and structural measures of the arcuate fasciculus. Results revealed an effect of degree of hand preference on arcuate fasciculus structure, such that consistently-handed individuals, regardless of the direction of hand preference, demonstrated the most asymmetric arcuate fasciculus, with larger left versus right arcuate, as measured by DTI. Functional language lateralization in Wernicke’s area, measured via fMRI, was related to arcuate fasciculus volume in consistent-left-handers only, and only in people who were not right hemisphere lateralized for language; given the small sample size for this finding, future investigation is warranted. Results suggest handedness degree may be an important variable to investigate in the context of neuroanatomical asymmetries.     

Functional cerebral asymmetries and cognitive abilities in musicians, painters, and controls

The relative participation of left- and right-hemisphere functions in verbal and spatial processing with musical composers, instrumentalists, painters, and non-musicians from student and junior high school populations was investigated. Hemispheric lateralization was related to the outcome of tests measuring spatial orientation, spatial visualization, tactile-visual discrimination, and verbal fluency. The relationship between lateral dominance and cognitive variables was influenced by sex and musical talents and the ability to paint. Males, irrespective of talents, were lateralized stronger than females. These sex differences were due to nonmusicians, only. Male and female composers, instrumentalists, and painters did not differ in language lateralization. Female left-handers showed a marked tendency for reversed language lateralization; left-handed males did not.     

The contribution of functional near-infrared spectroscopy (fNIRS) to the presurgical assessment of language function in children

Before performing neurosurgery, an exhaustive presurgical assessment is required, usually including an investigation of language cerebral lateralization. Among the available procedures, the intracarotid amobarbital test (IAT) was formerly the most widely used. However, this procedure has many limitations: it is invasive and potentially traumatic, especially for children. To overcome these limitations, neuroimaging techniques such as functional magnetic resonance imaging (fMRI) have been used. Again, these methods are difficult to use with children, who must remain motionless during data acquisition. Functional near-infrared spectroscopy (fNIRS) is a noninvasive functional imaging technique that is easily applied to pediatric and cognitively limited patients. It has been used recently in epileptic children for presurgical assessment of expressive and receptive language brain lateralization. The aim of this review is to present the contribution of fNIRS to the presurgical assessment of language function in children with neurological diseases.     

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 MEG's 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.     

The time course for language acquisition in biologically distinct populations: evidence from deaf individuals

The present study provides evidence that individuals who have different patterns of cerebral lateralization and who develop along different maturational time courses can attain comparable levels of language proficiency. Right-handed individuals with left-handed family members (left-handed familials, LHFs) showed a shorter sensitive period for language acquisition than did right-handed individuals with only right-handed family members (right-handed familials, RHFs). The shorter sensitive period for LHFs may be due to a focus on non-linguistic, word-based conceptual information during language acquisition. RHFs may focus on grammatical relations during language acquisition, which matures later than lexical knowledge. This suggests that there may be different patterns of cerebral lateralization for language in all normal populations as a function of familial handedness.     

Combined functional and causal connectivity analyses of language networks in children: a feasibility study

Instead of assessing activation in distinct brain regions, approaches to investigating the networks underlying distinct brain functions have come into the focus of neuroscience research. Here, we provide a completely data-driven framework for assessing functional and causal connectivity in functional magnetic resonance imaging (fMRI) data, employing Granger's causality. We investigate the networks underlying story processing in 17 healthy children (8f, 9m, 10.4+/-2.8 years, 6.5-15.4 years). Extensive functional connectivity exists between brain regions, including some not detected in standard random effects analyses. Causal connectivity analyses demonstrate a clear dominance of left-sided language regions for both forward and backward interactions with other network nodes. We believe our approach to be useful in helping to assess language networks in the normal or pathological setting; it may also aid in providing better starting estimates for the more hypothesis-driven approaches like structural equation or dynamic causal modeling.     

Sex differences in the IQ-white matter microstructure relationship: A DTI study

Sex differences in the relationship between general intelligence and brain structure are a topic of increasing research interest. Early studies focused mainly on gray and white matter differences using voxel-based morphometry, while more recent studies investigated neural fiber tracts using diffusion tensor imaging (DTI) to analyze the white matter microstructure. In this study we used tract-based spatial statistics (TBSS) on DTI to test how intelligence is associated with brain diffusion indices and to see whether this relationship differs between men and women. 63 Men and women divided into groups of lower and higher intelligence were selected. Whole-brain DTI scans were analyzed using TBSS calculating maps of fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). The results reveal that the white matter microstructure differs between individuals as a function of intelligence and sex. In men, higher intelligence was related to higher FA and lower RD in the corpus callosum. In women, in contrast, intelligence was not related to the white matter microstructure. The higher values of FA and lower values of RD suggest that intelligence is associated with higher myelination and/or a higher number of axons particularly in men. This microstructural difference in the corpus callosum may increase cognitive functioning by reducing inter-hemispheric transfer time and thus account for more efficient brain functioning in men.     

Neuroimaging studies of working memory:

We performed meta-analyses on 60 neuroimaging (PET and fMRI) studies of working memory (WM), considering three types of storage material (spatial, verbal, and object), three types of executive function (continuous updating of WM, memory for temporal order, and manipulation of information in WM), and interactions between material and executive function. Analyses of material type showed the expected dorsal-ventral dissociation between spatial and nonspatial storage in the posterior cortex, but not in the frontal cortex. Some support was found for left frontal dominance in verbal WM, but only for tasks with low executive demand. Executive demand increased right lateralization in the frontal cortex for spatial WM. Tasks requiring executive processing generally produce more dorsal frontal activations than do storage-only tasks, but not all executive processes show this pattern. Brodmann’s areas (BAs) 6, 8, and 9, in the superior frontal cortex, respond most when WM must be continuously updated and when memory for temporal order must be maintained. Right BAs 10 and 47, in the ventral frontal cortex, respond more frequently with demand for manipulation (including dual-task requirements or mental operations). BA 7, in the posterior parietal cortex, is involved in all types of executive function. Finally, we consider a potential fourth executive function: selective attention to features of a stimulus to be stored in WM, which leads to increased probability of activating the medial prefrontal cortex (BA 32) in storage tasks.     

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.     

Differences in language performance in variations of lateralization

Language proficiency was studied in 489 primary-school-aged children classified as extreme left-, extreme right-, mild left-, and mild right-handers on the basis of both hand-preference and hand-skill, using a test battery of seven measures. An ANOVA run on factor scores showed neither significant association of language proficiency with variations of lateralization regarding hand-preference and hand-skill nor differences in factor structure derived from a principal component analysis between extreme vs. mild hand-preference and hand-skill groups. Moreover, low language proficiency was not significantly associated with specific patterns of lateralization in hand-preference subgroups. In contrast, low language performers with poor hand-skill were significantly overrepresented both in the extreme left-handed group alone and when combined with the extreme right-handed, in comparison to mild left- and mild right-handed with respect to population. The data are not consistently accommodated by the theory of balanced polymorphism (mainly Annett, 1978, 1985 Annett & Manning, 1989 ). Alternately, factors such as lag of maturation ( Bishop, 1980, 1984, 1990a, 1990b ), delay of growth ( Geschwind & Galaburda, 1985b ), and developmental instability associated with unique patterns of variations in lateralization ( Yeo, Gangestad, & Daniel, 1993 ) are discussed as possible factors accounting for the present results.     

Neural correlates of metaphor processing: The roles of figurativeness,familiarity and difficulty

There is currently much interest in investigating the neural substrates of metaphor processing. In particular, it has been suggested that the right hemisphere plays a special role in the comprehension of figurative (non-literal) language, and in particular metaphors. However, some studies find no evidence of right hemisphere involvement in metaphor comprehension (e.g. [Lee, S. S., & Dapretto, M. (2006). Metaphorical vs. literal word meanings: fMRI evidence against a selective role of the right hemisphere. NeuroImage, 29, 536–544; Rapp, A. M., Leube, D. T., Erb, M., Grodd, W., & Kircher, T. T. J. (2004). Neural correlates of metaphor processing. Cognitive Brain Research, 20, 395–402]). We suggest that lateralization differences between literal and metaphorical language may be due to factors such as differences in familiarity ([Schmidt, G. L., DeBuse, C. J., & Seger, C. A. (2007). Right hemisphere metaphor processing? Characterizing the lateralization of semantic processes. Brain and Language, 100, 127–141]), or difficulty ([Bookheimer, S. (2002). Functional MRI of language: New approaches to understanding the cortical organization of semantic processing. Annual Review of Neuroscience, 25, 151–188; Rapp, A. M., Leube, D. T., Erb, M., Grodd, W., & Kircher, T. T. J. (2004). Neural correlates of metaphor processing. Cognitive Brain Research, 20, 395–402]) in addition to figurativeness. The purpose of this study was to separate the effects of figurativeness, familiarity, and difficulty on the recruitment of neural systems involved in language, in particular right hemisphere mechanisms. This was achieved by comparing neural activation using functional magnetic resonance imaging (fMRI) between four conditions: literal sentences, familiar and easy to understand metaphors, unfamiliar and easy to understand metaphors, and unfamiliar and difficult to understand metaphors. Metaphors recruited the right insula, left temporal pole and right inferior frontal gyrus in comparison with literal sentences. Familiar metaphors recruited the right middle frontal gyrus when contrasted with unfamiliar metaphors. Easy metaphors showed higher activation in the left middle frontal gyrus as compared to difficult metaphors, while difficult metaphors showed selective activation in the left inferior frontal gyrus as compared to easy metaphors. We conclude that the right hemisphere is involved in metaphor processing and that the factors of figurativeness, familiarity and difficulty are important in determining neural recruitment of semantic processing.     

Cognitive sex differences: speed and problem-solving strategies on computerized neuropsychological tasks

Skill, strategy, and laterality measures obtained through computerized neuropsychological tasks, a reaction time (RT) test, and a visuospatial problem-solving test, the Perceptual Maze Test, were analyzed in relation to sex and handedness of 56 high-school students. Boys were significantly faster than girls on most RT subtasks (including a response-inhibition task) and made more two-choice RT response errors for right-sided stimuli, which may be interpreted as resulting from a less cautious strategy. In maze performance, boys were superior to girls. An analysis of separate phases of the maze-solution process suggested that boys preferentially used an impulsive-global strategy. Girls, using a more reflective-sequential task-solving strategy, were significantly slower, without hitting more targets. Compared to all other groups, left-handed girls (strongly left-handed) had lower performance on maze tasks with no target information, particularly in left-sided solution pathways. Results were interpreted as reflecting differences in hemispheric competence and activation patterns between the sexes. Signs of a less differentiated lateralization and slight dysfunction of visuospatial skills in the left-handed girls were discussed.     

Reproducibility of fMRI-determined language lateralization in individual subjects

This study investigated within-subject test-retest reproducibility (i.e., reliability) of language lateralization obtained with fMRI. Nine healthy subjects performed the same set of three different language tasks during two fMRI sessions on separate days (verb generation, antonym generation, and picture naming). A fourth task analysis was added in which the three tasks were analyzed conjointly (combined task analysis, CTA). The CTA targets brain areas that are commonly used in different language tasks, aiming more selectively at language-critical structures. The number of active voxels (i.e., robustness) and calculated lateralization index (LI) were compared across sessions, tasks, subjects, and two a priori defined volumes of interest (classical language regions versus whole hemisphere) for a wide range of statistical thresholds. Robustness and reliability strongly varied between task analyses. The CTA was a robust detector of language-related brain activity, in contrast to the single task approaches. The CTA and verb generation task allowed for reliable calculation of the LI. Higher thresholds yielded a clear increase in left lateralization, which was largest when calculated from active voxels in classical language regions.     

Comparison of hemispheric activation during mental word and rhyme generation using transcranial Doppler sonography

The Wada test is at present the method of choice for preoperative assessment of patients who require surgery close to cortical language areas. It is, however, an invasive test with an attached morbidity risk. By now, an alternative to the Wada test is to combine a lexical word generation paradigm with non-invasive imaging techniques. However, results of this approach are still not in complete agreement with the findings of the Wada test (r = .92; Knecht, Deppe, Ebner et al., 1998). We attempted to obtain a more distinct language lateralization with the development of a phonological rhyme generation paradigm based on pseudoword stimuli. To examine the predictive value of both paradigms we performed simultaneous bilateral functional transcranial Doppler ultrasonography on 19 right-handed male native German subjects. The rhyme generation condition produced a significantly stronger lateralization to the supposed hemisphere of language dominance than the classical word generation condition. The observed differences suggest that the rhyme generation paradigm is more robust in detecting hemispheric language dominance than other neuropsychological paradigms and might be most valuable for preoperative assessment of cortical language areas.     

What Does Diffusion Tensor Imaging Reveal About the Brain and Cognition in Fetal Alcohol Spectrum Disorders?

Over the past 5 years, Diffusion Tensor Imaging (DTI) has begun to provide new evidence about the effects of prenatal alcohol exposure on white matter development. DTI, which examines microstructural tissue integrity, is sensitive to more subtle white matter abnormalities than traditional volumetric MRI methods. Thus far, the available DTI data suggest that white matter microstructural abnormalities fall on a continuum of severity in Fetal Alcohol Spectrum Disorder (FASD). Abnormalities are prominent in the corpus callosum, but also evident in major anterior-posterior fiber bundles, corticospinal tracts, and cerebellum. These subtle abnormalities are correlated with neurocognitive deficits, especially in processing speed, non-verbal ability, and executive functioning. Future studies using larger samples, increasingly sophisticated DTI methods, and additional functional MRI connectivity measures will better characterize the full range of abnormalities in FASD. Ultimately, these measures may serve as indices of change in future longitudinal studies and in studies of interventions for FASD.     

A general theory concerning the prenatal origins of cerebral lateralization in humans

The origins of cerebral lateralization in humans are traced to the asymmetric prenatal development of the ear and labyrinth. Aural lateralization is hypothesized to result from an asymmetry in craniofacial development, whereas vestibular dominance is traced to the position of the fetus during the final trimester. A right-ear sensitivity advantage may contribute to a left-hemispheric advantage in speech perception and language functions, whereas left-otolithic dominance may independently promote right-sided motoric dominance and a right-hemispheric superiority in most visuospatial functions. The emergence of handedness is linked to the assumption of an upright posture in the early hominids, whereas the failure to develop clear vestibular asymmetry may underlie the poor motoric lateralization found in several neurodevelopmental disorders.     

Comparing language lateralization determined by dichotic listening and fMRI activation in frontal and temporal lobes in children with epilepsy

We investigated the relationship between ear advantage scores on the Fused Dichotic Words Test (FDWT), and laterality of activation in fMRI using a verb generation paradigm in fourteen children with epilepsy. The magnitude of the laterality index (LI), based on spatial extent and magnitude of activation in classical language areas (BA 44/45, 21/22, 39) differed significantly for patients classified with unilateral left, compared to bilateral, language representation based on FDWT scores. Concordance with fMRI was higher for those classified with unilateral left, than bilateral language representation on the FDWT. Of note, asymmetry in temporal lobe, rather than frontal lobe, activation was more strongly related to the LI from the dichotic listening test. This study shows that the FDWT can provide a quick and valid estimate of lateralization in pre-surgical candidates, which can be readily adopted for other clinical or research purposes when an estimate of language dominance is desired.     

Atypical speech lateralization in adults with developmental coordination disorder demonstrated using functional transcranial Doppler ultrasound

Research using clinical populations to explore the relationship between hemispheric speech lateralization and handedness has focused on individuals with speech and language disorders, such as dyslexia or specific language impairment (SLI). Such work reveals atypical patterns of cerebral lateralization and handedness in these groups compared to controls. There are few studies that examine this relationship in people with motor coordination impairments but without speech or reading deficits, which is a surprising omission given the prevalence of theories suggesting a common neural network underlying both functions. We use an emerging imaging technique in cognitive neuroscience; functional transcranial Doppler (fTCD) ultrasound, to assess whether individuals with developmental coordination disorder (DCD) display reduced left‐hemisphere lateralization for speech production compared to control participants. Twelve adult control participants and 12 adults with DCD, but no other developmental/cognitive impairments, performed a word‐generation task whilst undergoing fTCD imaging to establish a hemispheric lateralization index for speech production. All participants also completed an electronic peg‐moving task to determine hand skill. As predicted, the DCD group showed a significantly reduced left lateralization pattern for the speech production task compared to controls. Performance on the motor skill task showed a clear preference for the dominant hand across both groups; however, the DCD group mean movement times were significantly higher for the non‐dominant hand. This is the first study of its kind to assess hand skill and speech lateralization in DCD. The results reveal a reduced leftwards asymmetry for speech and a slower motor performance. This fits alongside previous work showing atypical cerebral lateralization in DCD for other cognitive processes (e.g., executive function and short‐term memory) and thus speaks to debates on theories of the links between motor control and language production.