Atypical Language Organization Research Articles

Atypical language organization following perinatal infarctions of the left hemisphere is associated with structural changes in right-hemispheric grey matter.

To assess how atypical language organization after early left-hemispheric brain lesions affects grey matter in the contralesional hemisphere. This was a cross-sectional study with between-group comparisons of 14 patients (six female, 8-26 years) with perinatal left-hemispheric brain lesions (two arterial ischemic strokes, 11 periventricular haemorrhagic infarctions, one without classification) and 14 typically developing age-matched controls (TDC) with functional magnetic resonance imaging (fMRI) documented left-hemispheric language organization (six female, 8-28 years). MRI data were analysed with SPM12, CAT12, and custom scripts. Language lateralization indices were determined by fMRI within a prefrontal mask and right-hemispheric grey matter group differences by voxel-based morphometry (VBM). FMRI revealed left-dominance in seven patients with typical language organization (TYP) and right-dominance in seven patients with atypical language organization (ATYP) of 14 patients. VBM analysis of all patients versus controls showed grey matter reductions in the middle temporal gyrus of patients. A comparison between the two patient subgroups revealed an increase of grey matter in the middle frontal gyrus in the ATYP group. Voxel-based regression analysis confirmed that grey matter increases in the middle frontal gyrus were correlated with atypical language organization. Compatible with a non-specific lesion effect, we found areas of grey matter reduction in patients as compared to TDC. The grey matter increase in the middle frontal gyrus seems to reflect a specific compensatory effect in patients with atypical language organization. Perinatal stroke leads to decreased grey matter in the contralesional hemisphere. Atypical language organization is associated with grey matter increases in contralesional language areas.

Language network lateralization is reflected throughout the macroscale functional organization of cortex

Hemispheric specialization is a fundamental feature of human brain organization. However, it is not yet clear to what extent the lateralization of specific cognitive processes may be evident throughout the broad functional architecture of cortex. While the majority of people exhibit left-hemispheric language dominance, a substantial minority of the population shows reverse lateralization. Using twin and family data from the Human Connectome Project, we provide evidence that atypical language dominance is associated with global shifts in cortical organization. Individuals with atypical language organization exhibit corresponding hemispheric differences in the macroscale functional gradients that situate discrete large-scale networks along a continuous spectrum, extending from unimodal through association territories. Analyses reveal that both language lateralization and gradient asymmetries are, in part, driven by genetic factors. These findings pave the way for a deeper understanding of the origins and relationships linking population-level variability in hemispheric specialization and global properties of cortical organization.

Language Mapping With Magnetoencephalography: An Update on the Current State of Clinical Research and Practice With Considerations for Clinical Practice Guidelines.

Numerous studies have shown that language processing is not limited to a few brain areas. Visual or auditory stimuli activate corresponding cortical areas, then memory identifies the word or image, Wernicke's and Broca's areas support the processing for either reading/listening or speaking and many areas of the brain are recruited. Determining how a normal person processes language helps clinicians and scientist to understand how brain pathologies such as tumor or stroke can affect changes in language processing. Patients with epilepsy may develop atypical language organization. Over time, the chronic nature of epileptic activity, or changes from a tumor or stroke, can result in a shift of language processing area from the left to the right hemisphere, or re-routing of language pathways from traditional to non-traditional areas within the dominant left hemisphere. It is important to determine where these language areas are prior to brain surgery. MEG evoked responses reflecting cerebral activation of receptive and expressive language processing can be localized using several different techniques: Single equivalent current dipole, current distribution techniques or beamformer techniques. Over the past 20 years there have been at least 25 validated MEG studies that indicate MEG can be used to determine the dominant hemisphere for language processing. The use of MEG neuroimaging techniques is needed to reliably predict altered language networks in patients and to provide identification of language eloquent cortices for localization and lateralization necessary for clinical care.

A-37 Effects of Atypical Language Representation in Populations Suffering From Intractable Epilepsy

Abstract Objective Atypical language laterality, secondary to refractory epilepsy, presents complications to surgical planning/cognitive outcomes. Extant research shows the non-dominant hemisphere reallocates neural resources for language compensation in response to left-sided lesions (resulting in decreased visuoperceptual/visual memory). The present study examined relationships between 1) lesion location and atypical language organization and 2) lesion location/language laterality on performance on memory (California Verbal Memory Test 2nd-edition (CVLT; Delayed Recall), and visuoperceptual (Rey-Osterrieth Complex Figure Test, ROCFT; Copy) tests in relation to lesion location in a sample of patients with intractable epilepsy. Method Retrospective data was compiled on patients with refractory epilepsy undergoing interdisciplinary pre-surgical workup (N = 101), mean age of 37.2 (SD = 11.9) and mean education of 12.3 (SD = 3.7). The sample was then stratified by non-lesional (n = 48), left (n = 26), right (n = 21) or bilateral (n = 6) mesial temporal sclerosis (MTL); and, language laterality was confirmed by neuroradiologists via functional Magnetic Resonance Imaging (fMRI) scans. Results Analyses showed patients with left MTS were more likely to have atypical language organization, X2 (1, N = 47) = 6.6, p = .01. Moreover, significant differences on T-scores for CVLT, F (3,15) = 3.81, p = .04, 95% Cl [-1.73, -.08] and ROCFT, F(4,28) = 2.85, p = .046 95% Cl [31.62, 46.17] were found between groups stratified by lesion location/language laterality, respectively. Conclusions Organization of language in epileptic populations presents atypically in conjunction with left-sided lesions. Additionally, cognitive processes such as verbal memory and visuoperceptual abilities suffer based on lesion presence/location and language laterality in this fMRI confirmed sample.

From "rest" to language task: Task activation selects and prunes from broader resting-state network.

Resting-state networks (RSNs) show spatial patterns generally consistent with networks revealed during cognitive tasks. However, the exact degree of overlap between these networks has not been clearly quantified. Such an investigation shows promise for decoding altered functional connectivity (FC) related to abnormal language functioning in clinical populations such as temporal lobe epilepsy (TLE). In this context, we investigated the network configurations during a language task and during resting state using FC. Twenty-four healthy controls, 24 right and 24 left TLE patients completed a verb generation (VG) task and a resting-state fMRI scan. We compared the language network revealed by the VG task with three FC-based networks (seeding the left inferior frontal cortex (IFC)/Broca): two from the task (ON, OFF blocks) and one from the resting state. We found that, for both left TLE patients and controls, the RSN recruited regions bilaterally, whereas both VG-on and VG-off conditions produced more left-lateralized FC networks, matching more closely with the activated language network. TLE brings with it variability in both task-dependent and task-independent networks, reflective of atypical language organization. Overall, our findings suggest that our RSN captured bilateral activity, reflecting a set of prepotent language regions. We propose that this relationship can be best understood by the notion of pruning or winnowing down of the larger language-ready RSN to carry out specific task demands. Our data suggest that multiple types of network analyses may be needed to decode the association between language deficits and the underlying functional mechanisms altered by disease. Hum Brain Mapp 38:2540-2552, 2017. © 2017 Wiley Periodicals, Inc.

Delayed Development of Neural Language Organization in Very Preterm Born Children

This study investigates neural language organization in very preterm born children compared to control children and examines the relationship between language organization, age, and language performance. Fifty-six preterms and 38 controls (7–12 y) completed a functional magnetic resonance imaging language task. Lateralization and signal change were computed for language-relevant brain regions. Younger preterms showed a bilateral language network whereas older preterms revealed left-sided language organization. No age-related differences in language organization were observed in controls. Results indicate that preterms maintain atypical bilateral language organization longer than term born controls. This might reflect a delay of neural language organization due to very premature birth.

Atypical cortical language organization in epilepsy patients: evidence for divergent hemispheric dominance for receptive and expressive language function.

The central goal of presurgical language mapping is to identify brain regions that subserve cortical language function to minimize postsurgical language deficits. Presurgical language mapping in patients with epilepsy presents a key challenge because of the atypical pattern of hemispheric language dominance found in this population, with higher incidences of bilateral and right-biased language dominance than typical. In this prospective study, we combine magnetoencephalography with a panel of tasks designed to separately assess receptive and expressive function to provide a sensitive measure of language function in 15 candidates for resective surgery. We report the following: 4 of 15 patients (27%) showed left hemisphere dominance across all tasks, 4 of 15 patients (27%) showed right hemisphere dominance across all tasks, and 7 of 15 (46%) showed discordant language dominance, with right-dominant receptive and left-dominant expressive language. All patients with discordant language dominance showed this right-receptive and left-expressive pattern. Results provide further evidence supporting the importance of using a panel of tasks to assess separable aspects of language function. The clinical relevance of the findings is discussed, especially about current clinical operative measures for assessing language dominance, which use single hemisphere procedure (intracarotid amobarbital procedure and awake intraoperative stimulation) for determining language laterality.

Atypical language organization in temporal lobe epilepsy revealed by a passive semantic paradigm.

BackgroundMesial temporal lobe epilepsy (MTLE) is the most common type of focal epilepsy in adults and can be successfully cured by surgery. One of the main complications of this surgery however is a decline in language abilities. The magnitude of this decline is related to the degree of language lateralization to the left hemisphere. Most fMRI paradigms used to determine language dominance in epileptic populations have used active language tasks. Sometimes, these paradigms are too complex and may result in patient underperformance. Only a few studies have used purely passive tasks, such as listening to standard speech.MethodsIn the present study we characterized language lateralization in patients with MTLE using a rapid and passive semantic language task. We used functional magnetic resonance imaging (fMRI) to study 23 patients [12 with Left (LMTLE), 11 with Right mesial temporal lobe epilepsy (RMTLE)] and 19 healthy right-handed controls using a 6 minute long semantic task in which subjects passively listened to groups of sentences (SEN) and pseudo sentences (PSEN). A lateralization index (LI) was computed using a priori regions of interest of the temporal lobe.ResultsThe LI for the significant contrasts produced activations for all participants in both temporal lobes. 81.8% of RMTLE patients and 79% of healthy individuals had a bilateral language representation for this particular task. However, 50% of LMTLE patients presented an atypical right hemispheric dominance in the LI. More importantly, the degree of right lateralization in LMTLE patients was correlated with the age of epilepsy onset.ConclusionsThe simple, rapid, non-collaboration dependent, passive task described in this study, produces a robust activation in the temporal lobe in both patients and controls and is capable of illustrating a pattern of atypical language organization for LMTLE patients. Furthermore, we observed that the atypical right-lateralization patterns in LMTLE patients was associated to earlier age at epilepsy onset. These results are in line with the idea that early onset of epileptic activity is associated to larger neuroplastic changes.

Cerebellar language mapping and cerebral language dominance in pediatric epilepsy surgery patients.

ObjectiveChildren with epilepsy often have reorganization of language networks and abnormal brain anatomy, making determination of language lateralization difficult. We characterized the proportion and distribution of language task activation in the cerebellum to determine the relationship to cerebral language lateralization.MethodsForty-six pediatric epilepsy surgery candidates (aged 7–19 years) completed an fMRI auditory semantic decision language task. Distribution of activated voxels and language laterality indices were computed using: (a) Broca's and Wernicke's areas and their right cerebral homologues; and (b) left and right cerebellar hemispheres. Language task activation was anatomically localized in the cerebellum.ResultsLateralized language task activation in either cerebral hemisphere was highly correlated with lateralized language task activation in the contralateral cerebellar hemisphere (Broca vs. cerebellar: ρ = −0.54, p < 0.01). Cerebellar language activation was located within Crus I/II, areas previously implicated in non-motor functional networks.ConclusionsCerebellar language activation occurs in homologous regions of Crus I/II contralateral to cerebral language activation in patients with both right and left cerebral language dominance. Cerebellar language laterality could contribute to comprehensive pre-operative evaluation of language lateralization in pediatric epilepsy surgery patients. Our data suggest that patients with atypical cerebellar language activation are at risk for having atypical cerebral language organization.

Hand Preference in Developmental Stuttering: A Test of the Geschwind-Galaburda Hypothesis of Hemispheric Specialization (P07.178)

Objective: Our hypothesis was that people who stutter (PWS) are more likely to have atypical hand preference; to test this we measured the association of stuttering with gender and hand and foot preference. Background Geschwind and Galaburda postulated that functional inter-hemispheric differences reflect the extent of anatomical differences. From this idea they postulated that atypical cerebral lateralization underlies stuttering and thus stuttering would be associated with both left-handedness and gender. Design/Methods: Individuals on the Stuttering Foundation of America9s mailing list were asked to complete a mail survey and to distribute it to acquaintances. The survey included questions about gender, demographics and stuttering as well as 42-item hand-preference and 12-item foot-preference inventories (HPI and FPI, respectively). Results were analyzed using logistic regression. Results: Four-hundred-eighty-six subjects currently stuttered out of 863 responders. Handedness and gender were significant predictors of stuttering. Males were more likely to stutter than females [OR=7.7 95%CI(5,10) p Conclusions: Our results confirm our hypothesis that atypical laterality, as reflected on scores from a handedness survey, is a predictor of stuttering. This relationship is complex due to its interaction with sex-linked factors. Handedness and sex-linked factors may influence cortical development in PWS. From our results we postulate that how females respond to higher estrogen or lower testosterone exposure in utero can lead to both atypical language organization and hand preference. The process leading to stuttering in males may be different affecting only language organization. Supported by: Stuttering Foundation of America. Disclosure: Dr. Lovera has received personal compensation for activities with EMD Serono, Teva Neuroscience, and Biogen Idec as a consultant. Dr. Corey has nothing to disclose. Dr. Foundas has nothing to disclose.

Language Organization and Reorganization in Epilepsy

The vast majority of healthy individuals are left hemisphere dominant for language; however, individuals with left hemisphere epilepsy have a higher likelihood of atypical language organization. The cerebral organization of language in epilepsy has been studied with invasive procedures such as Wada testing and electrical cortical stimulation mapping (ESM), and more recently, with noninvasive neuroimaging techniques such as functional magnetic resonance imaging (fMRI). Investigators have used these techniques to explore the influence of unique clinical features inherent in epilepsy that might contribute to the reorganization of language, such as location of seizure onset, age of seizure onset, and extent of interictal epileptiform activity. In this paper, we review the contribution of these and other clinical variables to the lateralization and localization of language in epilepsy, and how these patient-related variables affect the results from these three different, yet complementary methodologies. Unlike the abrupt language changes that occur following acute brain injury with disruption of established language circuits, converging evidence suggests that the chronic nature of epileptic activity can result in a developmental shift of language from the left to the right hemisphere or re-routing of language pathways from traditional to non-traditional areas within the dominant left hemisphere. Clinical variables have been shown to contribute to cerebral language reorganization in the setting of chronic seizure disorders, yet such factors have not been reliable predictors of altered language networks in individual patients, underscoring the need for language lateralization and localization procedures when definitive identification of language cortex is necessary for clinical care.

Clinical functional MRI of the language domain in children with epilepsy

Functional MRI (fMRI) for the assessment of language functions is increasingly used in the diagnostic workup of patients with epilepsy. Termed "clinical fMRI," such an approach is also feasible in children who may display specific patterns of language reorganization. This study was aimed at assessing language reorganization in pediatric epilepsy patients, using fMRI. We studied 26 pediatric epilepsy patients (median age, 13.05 years; range, 5.6-18.7 years) and 23 healthy control children (median age, 9.37 years; range, 6.2-15.4 years), using two child-friendly fMRI tasks and adapted data-processing streams. Overall, 81 functional series could be analyzed. Reorganization seemed to occur primarily in homotopic regions in the contralateral hemisphere, but lateralization in the frontal as well as in the temporal lobes was significantly different between patients and controls. The likelihood to find atypical language organization was significantly higher in patients. Additionally, we found significantly stronger activation in the healthy controls in a primarily passive task, suggesting a systematic confounding influence of antiepileptic medication. The presence of a focal cortical dysplasia was significantly associated with atypical language lateralization. We conclude that important confounds need to be considered and that the pattern of language reorganization may be distinct from the patterns seen in later-onset epilepsy.

Why one task is not enough: Functional MRI for atypical language organization in two children

Functional MRI is increasingly used to determine the hemispheric dominance for language. This is especially relevant in children who may not be able to comply with the high demands of a Wada test. We here report on two children in which the full extent of language reorganization was only determined when two fMRI tasks were analyzed; in the first case, the results from the second task corroborated the shifted hemispheric dominance seen in the first task. In the second case, the second task showed an opposite hemispheric dominance, suggesting a hemispheric dissociation of language functions. These cases underline the necessity to use more than one fMRI task for the determination of hemispheric dominance, whenever possible. This is particularly relevant in children as unusual patterns of reorganization may be more likely.

Atypical Propositional Language Organization in Prenatal and Early-Acquired Temporal Lobe Lesions

This study investigated differences in propositional language organization in children with developmental and acquired brain lesions. We evaluated 30 right-handed subjects with intractable epilepsy due to either focal cortical dysplasia or hippocampal sclerosis with neuropsychological testing and functional MRI prior to epilepsy surgery. Atypical activations were seen in both prenatal and early postnatal lesions, but the contribution of specific histopathological substrate was minimal. Atypical organization of both temporal and frontal language areas also correlated inversely with receptive vocabulary scores. The data demonstrated a greater propensity toward atypical activation patterns for receptive than expressive networks, particularly when lesions were located in the dominant temporal lobe. Atypical language organization was not correlated with seizure-related factors such as age at onset or duration of epilepsy. The patterns of atypical language activation support prior studies implicating proximity of pathology to eloquent cortex in the dominant hemisphere as the primary determinant of functional reorganization.

The Verbal IQ/Performance IQ discrepancy as a sign of seizure focus laterality in pediatric patients with epilepsy

A large Verbal IQ (VIQ)/Performance IQ (PIQ) discrepancy has been viewed as a sign of lateralized brain dysfunction. The current study was conducted to determine if the presence of a large VIQ/PIQ discrepancy (⩾15 points) would accurately predict laterality of seizure foci in pediatric patients with epilepsy. A discrepancy score (VIQ − PIQ) was calculated for 130 children (mean age = 12.25) undergoing presurgical epilepsy evaluations. Patients were grouped on the basis of language mediation confirmed through the intracarotid amobarbital procedure. Large discrepancies were noted in 34% of the group with typical language and 24% of the children with atypical language organization. When present, this discrepancy accurately lateralized seizure focus for 79% of those with typical and 57% of those with atypical language organization. The presence of the discrepancy was unrelated to seizure control following surgery for the atypical language group. In the typical language group, 85% of children with discrepancies, but only 63% of children without discrepancies, achieved seizure control. Results suggest that the presence of a large discrepancy is not effective, by itself, in lateralizing seizure foci, but may contribute to refining predictions of surgical outcome.

Functional Magnetic Resonance Imaging Reveals Atypical Language Organization in Children Following Perinatal Left Middle Cerebral Artery Stroke

We used verb generation and story listening tasks during fMRI to study language organization in children (7, 9 and 12 years old) with perinatal left MCA infarctions. Healthy, age-matched comparison children (n = 39) showed activation in left Broca's area during the verb generation task; in contrast, stroke subjects showed activation either bilaterally or in the right hemisphere homologue during both tasks. In Wernicke's area, comparison subjects showed left lateralization (verb generation) and bilateral activation (L > R) (story listening). Stroke subjects instead showed bilateral or right lateralization (verb generation) and bilateral activation (R > L) (story listening). Language is distributed atypically in children with perinatal left hemisphere stroke.

Atypical Language Representation in Patients with Chronic Seizure Disorder and Achievement Deficits with Magnetoencephalography

To characterize the relation between hemispheric asymmetries in language-specific brain activity and reading/spelling achievement by using magnetoencephalography (MEG). Patients (n = 83) with medically intractable complex partial seizures of either left- or right-hemisphere origin were classified as having reading and/or spelling deficits (RS) or as not impaired (NI) by using standard achievement tests. All patients had undergone noninvasive functional mapping of receptive language cortex by using MEG as part of a preoperative seizure surgery evaluation. RS patients with left-hemisphere seizure onset exhibited relatively greater activation and earlier onset of late, language-specific MEG activity in posterior temporal and inferior parietal areas of the right as compared with the left hemisphere than did NI patients. These findings also were evident on an individual basis and were independent of global intellectual abilities. Reading and spelling achievement deficits in patients with complex partial seizures of left-hemisphere origin are associated with atypical language organization, possibly secondary to reorganization of language function to right-hemisphere areas that are not as efficient as homotopic areas in the left hemisphere in supporting reading and spelling functions.

Correlation between language organization and diffusion tensor abnormalities in refractory partial epilepsy.

Atypical language organization is more frequently found in patients with refractory partial epilepsy than in healthy controls; however, the reasons for this are not well known. Here we assess the relation between language laterality index (LI) and white-matter tract changes. Nine patients with refractory partial epilepsy were assessed with a 3-T GE scanner. Functional magnetic resonance imaging (fMRI) of language and diffusion tensor imaging (DTI) were acquired. For the fMRI, a noun-verb generation task was performed, all images were motion corrected, and activated pixels in classic language areas were counted. The DTI images were acquired in six standard directions with an initial non-diffusion-weighted scan. The "average anisotropy" was determined in a region of interest in the frontal lobe, temporal lobe, and parietal lobe white matter. An asymmetry index (AI) was calculated for language and DTI. Atypical language lateralization was diagnosed if the lateralization index (LI)-language was smaller than 0.4. Two of the nine patients had atypical language localization (LI-language, -0.6, and 0.3); both had left temporal DTI asymmetry (LI-DTI, -0.3 and -0.2). The remaining seven patients had typical language localization, and no marked DTI abnormalities. Asymmetry in temporal lobe DTI correlated with LI-language (r= 0.8; p = 0.006). Atypical language lateralization in patients with partial epilepsy may be associated with white-matter tract abnormalities.