fMRI study of language lateralization in children and adults

Language lateralization in the brain is dependent on family history of handedness, personal handedness, pathology, and other factors. The influence of age on language lateralization is not completely understood. Increasing left lateralization of language with age has been observed in children, while the reverse has been noted in healthy young adults. It is not known whether the trend of decreasing language lateralization with age continues in the late decades of life and at what age the inflection in language lateralization trend as a function of age occurs. In this study, we examined the effect of age on language lateralization in 170 healthy right-handed children and adults ages 5-67 using functional MRI (fMRI) and a verb generation task. Our findings indicate that language lateralization to the dominant hemisphere increases between the ages 5 and 20 years, plateaus between 20 and 25 years, and slowly decreases between 25 and 70 years.     

Cerebellar asymmetry,cortical asymmetry and handedness: Two independent networks

ABSTRACT

In 46 right-handers and 46 left-handers, we used functional magnetic resonance imaging to record activity in the frontal lobes while they generated words, the temporal lobe while they made synonym judgments, and the parietal lobe while they watched videos of manual actions. In each case we also recorded activity in the cerebellum. Laterality indices showed a significant left-hemispheric bias in each cortical lobe and a right-hemispheric bias in the cerebellum for the 2 language tasks, but not during action observation. Cerebellar asymmetry also correlated negatively with frontal and temporal asymmetry, reflecting contralateral connections, but not with parietal asymmetry. A factor analysis of the inter-correlations among laterality indices revealed 2 factors, implying independent lateralized networks, with cerebellar asymmetry strongly linked to a language network in frontal and temporal cortices, and handedness strongly linked to an action-observation network in the parietal lobe.     

Lateralization of the arcuate fasciculus and its differential correlation with reading ability between young learners and experienced readers: a diffusion tensor tractography study in a Chinese cohort

As Chinese reading engages a different neural network from alphabetic language reading, we investigate whether leftward lateralization of the arcuate fasciculus (AF), as observed in the Western population, is also present in the Chinese population and if it does, whether it is associated with better reading ability. Diffusion tensor tractography analysis on 75 Chinese subjects of three age groups (first graders, fourth graders, and college students) showed that 70-83% of them had leftward lateralization of the AF. The pattern of lateralization did not differ significantly among the three groups, suggesting that lateralization of the AF is formed at an early age and before one enters first grade. Among the first graders, who had just started to learn to read, subjects with strongly leftward lateralized AF scored significantly higher than those with other defined lateralization patterns in Chinese (P = 0.001) and English (P = 0.036) reading tasks. This association was not observed among the fourth graders and college students who were experienced Chinese readers. Among the fourth graders, females were found to obtain significantly higher Chinese (P = 0.033) and English reading scores than males (P = 0.002). Our study suggests a differential effect of leftward lateralization of the AF on reading ability at different stages of reading development in the Chinese population.     

Lateralization of the arcuate fasciculus from childhood to adulthood and its relation to cognitive abilities in children

The arcuate fasciculus is a major white matter tract involved in language processing that has also been repeatedly implicated in intelligence and reasoning tasks. Language in the human brain is lateralized in terms of both function and structure, and while the arcuate fasciculus reflects this asymmetry, its pattern of lateralization is poorly understood in children and adolescents. We used diffusion tensor imaging (DTI) and tractography to examine arcuate fasciculus lateralization in a large (n = 183) group of healthy right‐handed volunteers aged 5–30 years; a subset of 68 children aged 5–13 years also underwent cognitive assessments. Fractional anisotropy and number of streamlines of the arcuate fasciculus were both significantly higher in the left hemisphere than the right hemisphere in most subjects, although some subjects (10%) were right lateralized. Age and gender effects on lateralization were not significant. Children receiving cognitive assessments were divided into three groups: a “left‐only” group in whom only the left side of the arcuate fasciculus could be tracked, a left‐lateralized group, and a right‐lateralized group. Scores on the Peabody Picture Vocabulary Test (PPVT) and NEPSY Phonological Processing task differed significantly among groups, with left‐only subjects outperforming the right‐lateralized group on the PPVT, and the left‐lateralized children scoring significantly better than the right‐lateralized group on phonological processing. In summary, DTI tractography demonstrates leftward arcuate fasciculus lateralization in children, adolescents, and young adults, and reveals a relationship between structural white matter lateralization and specific cognitive abilities in children. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

Atypically rightward cerebral asymmetry in male adults with autism stratifies individuals with and without language delay

In humans, both language and fine motor skills are associated with left‐hemisphere specialization, whereas visuospatial skills are associated with right‐hemisphere specialization. Individuals with autism spectrum conditions (ASC) show a profile of deficits and strengths that involves these lateralized cognitive functions. Here we test the hypothesis that regions implicated in these functions are atypically rightward lateralized in individuals with ASC and, that such atypicality is associated with functional performance. Participants included 67 male, right‐handed adults with ASC and 69 age‐ and IQ‐matched neurotypical males. We assessed group differences in structural asymmetries in cortical regions of interest with voxel‐based analysis of grey matter volumes, followed by correlational analyses with measures of language, motor and visuospatial skills. We found stronger rightward lateralization within the inferior parietal lobule and reduced leftward lateralization extending along the auditory cortex comprising the planum temporale, Heschl's gyrus, posterior supramarginal gyrus, and parietal operculum, which was more pronounced in ASC individuals with delayed language onset compared to those without. Planned correlational analyses showed that for individuals with ASC, reduced leftward asymmetry in the auditory region was associated with more childhood social reciprocity difficulties. We conclude that atypical cerebral structural asymmetry is a potential candidate neurophenotype of ASC. Hum Brain Mapp 37:230–253, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Regional differences in the developmental trajectory of lateralization of the language network

The timing and developmental factors underlying the establishment of language dominance are poorly understood. We investigated the degree of lateralization of traditional frontotemporal and modulatory prefrontal‐cerebellar regions of the distributed language network in children (n = 57) ages 4 to 12—a critical period for language consolidation. We examined the relationship between the strength of language lateralization and neuropsychological measures and task performance. The fundamental language network is established by four with ongoing maturation of language functions as evidenced by strengthening of lateralization in the traditional frontotemporal language regions; temporal regions were strongly and consistently lateralized by age seven, while frontal regions had greater variability and were less strongly lateralized through age 10. In contrast, the modulatory prefrontal‐cerebellar regions were the least strongly lateralized and degree of lateralization was not associated with age. Stronger core language skills were significantly correlated with greater right lateralization in the cerebellum. Hum Brain Mapp 35:270–284, 2014. © 2012 Wiley Periodicals, Inc.     

Hand preference and sex shape the architecture of language networks

In right-handed subjects, language processing relies predominantly on left hemisphere networks, more so in men than in women, and in right- versus left-handers. Using DT-MRI tractography, we have shown that right-handed men are massively interconnected between the left-hemisphere language areas, whereas the homologous in the right hemisphere are sparse; interhemispheric connections between the language areas and their contralateral homologues are relatively strong. Women and left-handed men have equally strong intrahemispheric connections in both hemispheres, but women have a higher density of interhemispheric connections.     

Reduced left uncinate fasciculus fractional anisotropy in deficit schizophrenia but not in non-deficit schizophrenia

Aims: Schizophrenia is a psychiatric disorder manifesting with heterogeneous symptom clusters and clinical presentations. The deficit syndrome is the condition defined by the existence of primarily negative symptoms, and patients with the deficit syndrome differ from non‐deficit patients on measures of brain structure and function. In the current study, by using diffusion tensor imaging (DTI), we investigated the frontotemporal connectivity that is hypothesized to differ between deficit and non‐deficit schizophrenia. Methods: Twenty‐nine patients and 17 healthy controls were included in the study. The patients had deficit (n = 11) or non‐deficit (n = 18) schizophrenia and they were evaluated clinically with the Schedule for Deficit Syndrome (SDS) and Positive and Negative Syndrome Scale (PANSS). Diffusion‐based images were obtained with a 1.5T Siemens Magnetic Resonance Imaging machine and analyses were carried out with Functional Magnetic Resonance Imaging of the Brain Library Software – Diffusion tool box software. Results: The fractional anisotropy values in the left uncinate fasciculus of schizophrenia patients with the deficit syndrome were lower than those of non‐deficit patients and the controls. There were no differences between non‐deficit schizophrenia patients and controls. Conclusion: These findings provide evidence of left uncinate fasciculus damage resulting in disrupted communication between orbitofrontal prefrontal areas and temporal areas in deficit schizophrenia patients.     

Presurgical functional transcranial Doppler sonography (fTCD) with intravenous echo enhancing agent SonoVue enables determination of language lateralization in epilepsy patients with poor temporal bone windows

Presurgical determination of language lateralization is important for planning and outcome estimation of neurosurgical interventions in patients with drug-refractory epilepsy. Functional transcranial Doppler sonography (fTCD) provides an established measure for language lateralization using the temporal bone windows for continuous recording of the cerebral blood flow velocity (CBFV) in both middle cerebral arteries (MCAs). However, because of insufficient temporal bone windows, fTCD cannot be applied properly in every patient. Here, we established stable and sufficient CBFV signals in both MCAs using continuous intravenous application of echo-enhancing agent SonoVue in 7 of 10 patients with poor temporal bone windows and were thus able to determine language lateralization. We conclude that the application of SonoVue can solve one principal disadvantage of fTCD and improves the applicability of the technique as a presurgical functional language lateralization procedure.     

Concurrent counting and typing: lateralized interference depends on a difference between the hands in motor skill

In previous demonstrations of differences between left- and right-handers in dual-task performance, participants' hand preference has been confounded with asymmetry of manual skill. The present study was designed to disentangle those two factors as sources of lateralized interference in the concurrent-task paradigm. Forty-eight normal adults (24 females and 24 males) counted backward by ones or by twos while typing an easy or difficult sequence of letters with either hand. When participants were grouped according to self-reported hand preference, both groups showed bilaterally symmetric slowing, relative to single-task conditions. However, when the same participants were grouped according to manual asymmetry in the baseline condition, the cognitive task interfered significantly more with the faster hand than with the slower hand. Baseline typing rate, averaged across hands, did not influence dual-task interference. Both self-reported left-hand preference and left-hand superiority in baseline typing were associated with reduced interference on the cognitive task, and the reduced interference in those groups seemed to reflect relatively loose coupling between manual and cognitive tasks. The results support and extend Caroselli et al.'s (1997) findings regarding the effect of baseline manual asymmetry on the pattern of dual-task interference. Irrespective of the participant's hand preference, the presence or absence of baseline asymmetry may be sufficient to determine whether dual-task interference is lateralized.     

The development of hand preference and dichotic language lateralization in males and females with congenital adrenal hyperplasia

ABSTRACT

People with congenital adrenal hyperplasia (CAH) are exposed to elevated levels of androgens in utero due to overproduction by the adrenal cortex. In order to test whether high levels of prenatal androgens influence the development of handedness preferences and left-hemisphere language representation, we studied 39 patients with CAH (28 females, 11 males) and 25 unaffected sibling controls (17 females, 8 males). Hand preference for 15 unimanual activities was evaluated via questionnaire and pantomime, and a consonant–vowel dichotic listening test was administered. Contemporary theories disagree as to whether high testosterone is said to increase or decrease the probability of developing a typical right-hand preference. Results showed no significant differences on the handedness inventory. Relative to controls, however, patients with CAH showed a significantly larger right-ear advantage on the dichotic syllables task, indicating stronger left-hemisphere lateralization of language. These results support an emerging body of evidence suggesting that high testosterone may bias lateralized development toward the population norm, but run counter to the Geschwind–Behan–Galaburda model which associates high prenatal testosterone with a greater prevalence of left-handedness.     

Gray and white matter asymmetries in healthy individuals aged 21-29 years: a voxel-based morphometry and diffusion tensor imaging study

The hemispheres of the human brain are functionally and structurally asymmetric. The study of structural asymmetries provides important clues to the neuroanatomical basis of lateralized brain functions. Previous studies have demonstrated age-related changes in morphology and diffusion properties of brain tissue. In this study, we simultaneously explored gray and white matter asymmetry using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) in 109 young healthy individuals (58 females and 51 males). To eliminate the potential confounding effects of aging and handedness, we restricted the study to right-handed subjects aged 21-29 years. VBM and voxel-based analysis of fractional anisotropy (FA) maps derived from DTI revealed a number of gray matter volume asymmetries (including the right frontal and left occipital petalias and leftward asymmetry of the planum temporale) and white matter FA asymmetries (including leftward asymmetry of the arcuate fasciculus, cingulum, and corticospinal tract). There was no significant effect of sex on gray and white matter asymmetry. Leftward volume asymmetry of the planum temporale and leftward FA asymmetry of the arcuate fasciculus were simultaneously demonstrated. Post hoc analysis showed that the gray matter volume of the planum temporale and FA of the arcuate fasciculus were positively related (Pearson correlation coefficient, 0.43; P < 0.0001). The results of our study demonstrate gray and white matter asymmetry in right-handed healthy young adults and suggest that leftward volume asymmetry of the planum temporale and leftward FA asymmetry of the arcuate fasciculus may be related.     

Reading impairment in a patient with missing arcuate fasciculus

We describe the case of a child (“S”) who was treated with radiation therapy at age 5 for a recurrent malignant brain tumor. Radiation successfully abolished the tumor but caused radiation-induced tissue necrosis, primarily affecting cerebral white matter. S was introduced to us at age 15 because of her profound dyslexia. We assessed cognitive abilities and performed diffusion tensor imaging (DTI) to measure cerebral white matter pathways. Diffuse white matter differences were evident in T1-weighted, T2-weighted, diffusion anisotropy, and mean diffusivity measures in S compared to a group of 28 normal female controls. In addition, we found specific white matter pathway deficits by comparing tensor-orientation directions in S's brain with those of the control brains. While her principal diffusion direction maps appeared consistent with those of controls over most of the brain, there were tensor-orientation abnormalities in the fiber tracts that form the superior longitudinal fasciculus (SLF) in both hemispheres. Tractography analysis indicated that the left and right arcuate fasciculus (AF), as well as other tracts within the SLF, were missing in S. Other major white matter tracts, such as the corticospinal and inferior occipitofrontal pathways, were intact. Functional MRI measurements indicated left-hemisphere dominanance for language with a normal activation pattern. Despite the left AF abnormality, S had preserved oral language with average sentence repetition skills. In addition to profound dyslexia, S exhibited visuospatial, calculation, and rapid naming deficits and was impaired in both auditory and spatial working memory. We propose that the reading and visuospatial deficits were due to the abnormal left and right SLF pathways, respectively. These results advance our understanding of the functional significance of the SLF and are the first to link radiation necrosis with selective damage to a specific set of fiber tracts.     

An epigenetic induction of a right-shift in hippocampal asymmetry: selectivity for short- and long-term potentiation but not post-tetanic potentiation

In humans, it is well established that major psychological functions are asymmetrically represented between the left and right cerebral cortices. The developmental origin of such functional lateralization remains unknown. Using the rat as a model system, we examined whether exposing neonates briefly to a novel environment can differentially affect synaptic plasticity in the left and right hippocampi during adulthood. During the first 3 weeks of life, one half of the pups from a litter spent 3 min daily away from their familiar home environment (Novel) while their littermates remained in that familiar environment (Home). At adulthood (7-months old), post-tetanic potentiation (PTP) of excitatory post-synaptic potentials (EPSPs), a very short-lasting form of plasticity, was greater among the Novel than the Home rats in both left and right hippocampi. In contrast, the novelty-induced increases in short- and long-term potentiation (STP, LTP), two relatively longer-lasting forms of plasticity, were found only in the right hippocampus. These findings demonstrate that a phase-selective asymmetry in hippocampal synaptic plasticity can be induced epigenetically by seemingly small systematic differences in early life environment. The selectivity of this asymmetry for the longer-lasting forms of synaptic plasticity suggests that the observed asymmetry in plasticity may contribute specifically to an asymmetric learning process which, in turn, may contribute to a functional asymmetry in the neocortex.     

Plasticity of lateralization: schooling predicts hand preference but not hand skill asymmetry in a non-industrial society

Considerable variation in the frequency of left-handedness between cultures has been reported, ranging from 0.5 to 24%. This variation in hand preference may have evolved under natural or cultural selection. It has been suggested that schooling affects handedness but as in most human societies only a selected and minor part of the population does not attend school this is difficult to test. We investigated to what extent schooling affects both hand preference and asymmetry in hand skill in a non-industrial population in the highlands of New Guinea. This provided unique opportunities because of the relatively recent establishment of a primary school in this population, and where people still live a non-industrial traditional life reflecting conditions in which handedness may have evolved. We interviewed 620 inhabitants (aged 5-70 y) to collect demographic data and school history, tested hand preference on 10 ecologically relevant activities, and measured performance of each hand on three tasks (pegboard, grip force, ball throwing). Schooled individuals were overall faster in fine motor performance, had greater grip strength and greater throwing accuracy. This suggests that there is implicit selection on the fitter part of the population to enter school. Schooling is associated with hand preference, as schooled individuals were more likely to be extremely right-handed and less likely to be strongly right-handed, but not with asymmetry of hand skill (controlled for sex and age). Developmental plasticity in hand preference but not skill asymmetry, and the weak correlations between hand preference and hand skill asymmetry indicate that they represent different aspects of brain lateralization. Furthermore, the weak correlations between hand preference and hand skill asymmetry leave room for moderating factors such as schooling, sex and age to have a differential effect on hand preference and hand skill, and each needs to be studied in its own right.     

Aberrations in the arcuate fasciculus are associated with auditory verbal hallucinations in psychotic and in non‐psychotic individuals

The pathophysiology of auditory verbal hallucinations (AVH) is still unclear. Cognitive as well as electrophysiological studies indicate that a defect in sensory feedback (corollary discharge) may contribute to the experience of AVH. This could result from disruption of the arcuate fasciculus, the major tract connecting frontal and temporo‐parietal language areas. Previous diffusion tensor imaging studies indeed demonstrated abnormalities of this tract in schizophrenia patients with AVH. It is, however, difficult to disentangle specific associations with AVH in this patient group as many other factors, such as other positive and negative symptoms, medication or halted education could likewise have affected tract integrity. We therefore investigated AVH in relative isolation and studied a group of non‐psychotic individuals with AVH as well as patients with AVH and non‐hallucinating matched controls. We compared tract integrity of the arcuate fasiculus and of three other control tracts, between 35 non‐psychotic individuals with AVH, 35 schizophrenia patients with AVH, and 36 controls using diffusion tensor imaging and magnetization transfer imaging. Both groups with AVH showed an increase in magnetization transfer ratio (MTR) in the arcuate fasciculus, but not in the other control tracts. In addition, a general decrease in fractional anisotropy (FA) for almost all bundles was observed in the patient group, but not in the non‐psychotic individuals with AVH. As increased MTR in the arcuate fasciculus was present in both hallucinating groups, a specific association with AVH seems plausible. Decreases in FA, on the other hand, seem to be related to other disease processes of schizophrenia. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

Lateralization of language function in epilepsy patients: A high-density scalp-derived event-related potentials (ERP) study

Objectives

Language functional magnetic resonance imaging (fMRI) represents the clinical standard for language lateralization assessment in presurgical epilepsy evaluation, but still many patients experience postoperative language deficits. Event-related potentials (ERPs), especially the negative component around and after 400 ms, are related to language processing and could therefore represent a complementary method of language lateralization assessment.

The nature of abnormal language processing in euthymic bipolar I disorder: evidence for a relationship between task demand and prefrontal function

OBJECTIVES: Abnormal language processing is a consistent finding in bipolar disorder (BD). We used functional magnetic resonance imaging (fMRI) to investigate the core components of language processing as well as the impact of task demand in a group of bipolar subjects. METHODS: Twelve euthymic dextral male BD I participants receiving lithium monotherapy were matched with 12 controls. Groups were matched for age, years of education and estimated premorbid IQ. We employed a factorial design manipulating task demand (decision versus fluency) and task domain (phonetic versus semantic) to investigate differences in language processing between groups and across different task domains and requirements. Data were fitted to haemodynamic response models convolved to the experimental design. Group and task difference maps were generated. RESULTS: During the scanning session bipolar patients demonstrated significantly slower reaction times. However, groups demonstrated the same task accuracy except for one domain (phonetic decision). All participants activated regions known to be engaged by language tasks, but compared to controls the bipolar patients showed altered patterns of prefrontal activation which were related to the nature of the task, language processing, and increasing task demand. CONCLUSIONS: We have demonstrated abnormal prefrontal activation in bipolar patients across a range of language tasks with varying task demands.     

Structural and functional underconnectivity as a negative predictor for language in autism

The development of language, social interaction, and communicative skills are remarkably different in the child with autism spectrum disorder (ASD). Atypical brain connectivity has frequently been reported in this patient population. However, the interplay between their brain connectivity and language performance remains largely understudied. Using diffusion tensor imaging tractography and resting‐state fMRI, the authors explored the structural and functional connectivity of the language network and its relation to the language profile in a group of healthy control subjects (N = 25) and a group of children with ASD (N = 17). The authors hypothesized that in children with ASD, a neural connectivity deficit of the language network can be related to the observed abnormal language function. They found an absence of the right‐hemispheric arcuate fascicle (AF) in 28% (7/25) of the healthy control children and in 59% (10/17) of the children with ASD. In contrast to healthy control children, the absence of the right‐hemispheric AF in children with autism was related to a lower language performance as indicated by a lower verbal IQ, lower scores on the Peabody Picture Vocabulary Test, and lower language scores on the Dutch version of the Clinical Evaluation of Language Fundamentals (CELF‐4NL). In addition, through iterative fMRI data analyses, the language impairment of children with ASD could be linked to a marked loss of intrahemispheric functional connectivity between inferior frontal and superior temporal regions, known as the cortical language network. Both structural and functional underconnectivity patterns coincide and are related to an abnormal language function in children with ASD. Hum Brain Mapp 35:3602–3615, 2014. © 2013 Wiley Periodicals, Inc .