Covert Verb Generation Research Articles

Alternative language paradigms for functional magnetic resonance imaging as presurgical tools for inducing crossed cerebro-cerebellar language activations in brain tumor patients.

Crossed cerebro-cerebellar BOLD activations have recently come to light as additional diagnostic features for patients with brain tumors. The covert verb generation (VG) task is a widely used language paradigm to determine these language-related crossed activations. Here we demonstrate these crossed activations in two additional language paradigms, the semantic and phonological association tasks. We propose the merit of these tasks to language lateralization determination in the clinic as they are easy to monitor and suitable for patients with aphasia. Patients with brain tumors localized at different cortical sites (n = 71) performed three language paradigms, namely the VG task as well as the semantic (SA) and phonological (PA) association tasks with button-press responses. Respective language activations in disparate cortical regions and the cerebellum were assigned laterality. Agreements in laterality between the two new tasks and the verb generation task were tested using Cohen's kappa. Both tasks significantly agreed in cortical and cerebellar lateralization with the verb generation task in patients. Additionally, a McNemar test confirmed the presence of crossed activations in the cortex and the cerebellum in the entire subject population. We demonstrated that the semantic and phonological association tasks resulted in crossed cerebro-cerebellar language lateralization activations as those observed due to the covert verb generation task. This may suggest the possibility of these tasks being used conjointly with the traditional verb generation task, especially for subjects that may be unable to perform the latter. • The semantic and phonological association tasks can be useful as additional presurgical fMRI language lateralization paradigms for brain tumor patients along with the standard verb generation task. • All three tasks also confirm the presence of crossed cerebro-cerebellar language activations in the current subject population.

Beta synchrony for expressive language lateralizes to right hemisphere in development

A left perisylvian network is known to support language in healthy adults. Low-beta (13–23 Hz) event-related desynchrony (ERD) has been observed during verb generation, at approximately 700–1200 ms post-stimulus presentation in past studies; the signal is known to reflect increased neuronal firing and metabolic demand during language production. In contrast, concurrent beta event-related synchrony (ERS) is thought to reflect neuronal inhibition but has not been well studied in the context of language. Further, while low-beta ERD for expressive language has been found to gradually shift from bilateral in childhood to left hemispheric by early adulthood, developmental lateralization of ERS has not been established. We used magnetoencephalography to study low beta ERS lateralization in a group of children and adolescents (n = 78), aged 4 to less than 19 years, who performed covert verb generation. We found that the youngest children had bilateral ERD and ERS. By adolescence, low-beta ERD was predominantly left lateralized in perisylvian cortex (i.e., Broca’s and Wernicke’s regions), while beta ERS was predominantly right lateralized. Increasing lateralization was significantly correlated to age for both ERD (Spearman’s r = 0.45, p < 0.01) and ERS (Spearman’s r = − 0.44, p < 0.01). Interestingly, while ERD lateralized in a linear manner, ERS lateralization followed a nonlinear trajectory, suggesting distinct developmental trajectories. Implications to early-age neuroplasticity and neuronal inhibition are discussed.

Cognitive neuroscience using wearable magnetometer arrays: Non-invasive assessment of language function

Recent work has demonstrated that Optically Pumped Magnetometers (OPMs) can be utilised to create a wearable Magnetoencephalography (MEG) system that is motion robust. In this study, we use this system to map eloquent cortex using a clinically validated language lateralisation paradigm (covert verb generation: 120 trials, ∼10 min total duration) in healthy adults (n = 3). We show that it is possible to lateralise and localise language function on a case by case basis using this system. Specifically, we show that at a sensor and source level we can reliably detect a lateralising beta band (15–30 Hz) desynchronization in all subjects. This is the first study of human cognition using OPMs and not only highlights this technology's utility as tool for (developmental) cognitive neuroscience but also its potential to contribute to surgical planning via mapping of eloquent cortex, especially in young children.

Recovering two languages with the right hemisphere

Converging evidence suggests that the right hemisphere (RH) plays an important role in language recovery from aphasia after a left hemisphere (LH) lesion. In this longitudinal study we describe the neurological, cognitive, and linguistic profile of A.C., a bilingual who, after a severe traumatic brain injury, developed a form of fluent aphasia that affected his two languages (i.e., Romanian and Italian). The trauma-induced parenchymal atrophy led to an exceptional ventricular dilation that, gradually, affected the whole left hemisphere. A.C. is now recovering both languages relying only on his right hemisphere. An fMRI experiment employing a bilingual covert verb generation task documented the involvement of the right middle temporal gyrus in processes of lexical selection and access. This case supports the hypothesis that the RH plays a role in language recovery from aphasia when the LH has suffered massive lesions.

Interhemispheric Plasticity following Intermittent Theta Burst Stimulation in Chronic Poststroke Aphasia.

The effects of noninvasive neurostimulation on brain structure and function in chronic poststroke aphasia are poorly understood. We investigated the effects of intermittent theta burst stimulation (iTBS) applied to residual language-responsive cortex in chronic patients using functional and anatomical MRI data acquired before and after iTBS. Lateralization index (LI) analyses, along with comparisons of inferior frontal gyrus (IFG) activation and connectivity during covert verb generation, were used to assess changes in cortical language function. Voxel-based morphometry (VBM) was used to assess effects on regional grey matter (GM). LI analyses revealed a leftward shift in IFG activity after treatment. While left IFG activation increased, right IFG activation decreased. Changes in right to left IFG connectivity during covert verb generation also decreased after iTBS. Behavioral correlations revealed a negative relationship between changes in right IFG activation and improvements in fluency. While anatomical analyses did not reveal statistically significant changes in grey matter volume, the fMRI results provide evidence for changes in right and left IFG function after iTBS. The negative relationship between post-iTBS changes in right IFG activity during covert verb generation and improvements in fluency suggests that iTBS applied to residual left-hemispheric language areas may reduce contralateral responses related to language production and facilitate recruitment of residual language areas after stroke.

A test-retest fMRI dataset for motor, language and spatial attention functions

BackgroundSince its inception over twenty years ago, functional magnetic resonance imaging (fMRI) has been used in numerous studies probing neural underpinnings of human cognition. However, the between session variance of many tasks used in fMRI remains understudied. Such information is especially important in context of clinical applications. A test-retest dataset was acquired to validate fMRI tasks used in pre-surgical planning. In particular, five task-related fMRI time series (finger, foot and lip movement, overt verb generation, covert verb generation, overt word repetition, and landmark tasks) were used to investigate which protocols gave reliable single-subject results. Ten healthy participants in their fifties were scanned twice using an identical protocol 2–3 days apart. In addition to the fMRI sessions, high-angular resolution diffusion tensor MRI (DTI), and high-resolution 3D T1-weighted volume scans were acquired.FindingsReliability analyses of fMRI data showed that the motor and language tasks were reliable at the subject level while the landmark task was not, despite all paradigms showing expected activations at the group level. In addition, differences in reliability were found to be mostly related to the tasks themselves while task-by-motion interaction was the major confounding factor.ConclusionsTogether, this dataset provides a unique opportunity to investigate the reliability of different fMRI tasks, as well as methods and algorithms used to analyze, de-noise and combine fMRI, DTI and structural T1-weighted volume data.

Single subject fMRI test–retest reliability metrics and confounding factors

While the fMRI test-retest reliability has been mainly investigated from the point of view of group level studies, here we present analyses and results for single-subject test-retest reliability. One important aspect of group level reliability is that not only does it depend on between-session variance (test-retest), but also on between-subject variance. This has partly led to a debate regarding which reliability metric to use and how different sources of noise contribute to between-session variance. Focusing on single subject reliability allows considering between-session only. In this study, we measured test-retest reliability in four behavioural tasks (motor mapping, covert verb generation, overt word repetition, and a landmark identification task) to ensure generalisation of the results and at three levels of data processing (time-series correlation, t value variance, and overlap of thresholded maps) to understand how each step influences the other and how confounding factors influence reliability at each of these steps. The contributions of confounding factors (scanner noise, subject motion, and coregistration) were investigated using multiple regression and relative importance analyses at each step. Finally, to achieve a fuller picture of what constitutes a reliable task, we introduced a bootstrap technique of within- vs. between-subject variance. Our results show that (i) scanner noise and coregistration errors have little contribution to between-session variance (ii) subject motion (especially correlated with the stimuli) can have detrimental effects on reliability (iii) different tasks lead to different reliability results. This suggests that between-session variance in fMRI is mostly caused by the variability of underlying cognitive processes and motion correlated with the stimuli rather than technical limitations of data processing.

Different patterns of language activation in post-stroke aphasia are detected by overt and covert versions of the verb generation fMRI task

SummaryBackgroundPost-stroke language functions depend on the relative contributions of the dominant and non-dominant hemispheres. Thus, we aimed to identify the neural correlates of overt and covert verb generation in adult post-stroke aphasia.Material/MethodsSixteen aphasic LMCA stroke patients (SPs) and 32 healthy controls (HCs) underwent language testing followed by fMRI while performing an overt event-related verb generation task (ER-VGT) isolating activations related to noun-verb semantic processing or to articulation and auditory processing, and a covert block design verb generation task (BD-VGT).ResultsBD-VGT activation patterns were consistent with previous studies, while ER-VGT showed different patterns in SPs relative to HCs including less left-hemispheric involvement during semantic processing and predominantly right-sided activation related to articulation and auditory processing. ER-VGT intra-scanner performance was positively associated with activation during semantic associations in the left middle temporal gyrus for HCs (p=0.031) and left middle frontal gyrus for SPs (p=0.042). Increased activation in superior frontal/cingulate gyri was associated with better intra-scanner performance (p=0.020). Lesion size negatively impacted verbal fluency tested with Controlled Oral Word Association Test (p=0.0092) and the Semantic Fluency Test (p=0.033) and trended towards a negative association with verb generation performance on the event-related verb generation task (p=0.081).ConclusionsGreater retention of pre-stroke language skills is associated with greater involvement of the left hemisphere with different cortical recruitment patterns observed in SPs versus HCs. Post-stroke verbal fluency may depend more upon the structural and functional integrity of the dominant left hemisphere language network rather than the shift to contralateral homologues.

Theta-Modulated Gamma-Band Synchronization Among Activated Regions During a Verb Generation Task

Expressive language is complex and involves processing within a distributed network of cortical regions. Functional MRI and magnetoencephalography (MEG) have identified brain areas critical for expressive language, but how these regions communicate across the network remains poorly understood. It is thought that synchronization of oscillations between neural populations, particularly at a gamma rate (>30 Hz), underlies functional integration within cortical networks. Modulation of gamma rhythms by theta-band oscillations (4–8 Hz) has been proposed as a mechanism for the integration of local cell coalitions into large-scale networks underlying cognition and perception. The present study tested the hypothesis that these oscillatory mechanisms of functional integration were present within the expressive language network. We recorded MEG while subjects performed a covert verb generation task. We localized activated cortical regions using beamformer analysis, calculated inter-regional phase locking between activated areas, and measured modulation of inter-regional gamma synchronization by theta phase. The results show task-dependent gamma-band synchronization among regions activated during the performance of the verb generation task, and we provide evidence that these transient and periodic instances of high-frequency connectivity were modulated by the phase of cortical theta oscillations. These findings suggest that oscillatory synchronization and cross-frequency interactions are mechanisms for functional integration among distributed brain areas supporting expressive language processing.

Characterizing the Normal Developmental Trajectory of Expressive Language Lateralization Using Magnetoencephalography

To characterize the developmental trajectory for expressive language representation and to test competing explanations for the relative neuroplasticity of language in childhood, we studied 28 healthy children and adolescents (aged 5-19 years) participating in a covert verb generation task in magnetoencephalography. Lateralization of neuromagnetic responses in the frontal lobe was quantified using a bootstrap statistical thresholding procedure for differential beamformer analyses. We observed a significant positive correlation between left hemisphere lateralization and age. Findings suggest that adult-typical left hemisphere lateralization emerges from an early bilateral language network, which may explain the pediatric advantage for interhemispheric plasticity of language.

A Linear Structural Equation Model for Covert Verb Generation Based on Independent Component Analysis of fMRI Data from Children and Adolescents

Human language is a complex and protean cognitive ability. Young children, following well defined developmental patterns learn language rapidly and effortlessly producing full sentences by the age of 3 years. However, the language circuitry continues to undergo significant neuroplastic changes extending well into teenage years. Evidence suggests that the developing brain adheres to two rudimentary principles of functional organization: functional integration and functional specialization. At a neurobiological level, this distinction can be identified with progressive specialization or focalization reflecting consolidation and synaptic reinforcement of a network (Lenneberg, 1967; Muller et al., 1998; Berl et al., 2006). In this paper, we used group independent component analysis and linear structural equation modeling (McIntosh and Gonzalez-Lima, 1994; Karunanayaka et al., 2007) to tease out the developmental trajectories of the language circuitry based on fMRI data from 336 children ages 5–18 years performing a blocked, covert verb generation task. The results are analyzed and presented in the framework of theoretical models for neurocognitive brain development. This study highlights the advantages of combining both modular and connectionist approaches to cognitive functions; from a methodological perspective, it demonstrates the feasibility of combining data-driven and hypothesis driven techniques to investigate the developmental shifts in the semantic network.

Language lateralization in left-handed patients with schizophrenia

We evaluated hemispheric lateralization of language production in non-right-handed (NRH) patients with schizophrenia compared with matched right-handed (RH) patients, NRH control, and RH control subjects. First, the ability to generate verbs during overt training trials was checked in 78 subjects. They were then evaluated with functional magnetic resonance imaging (fMRI) while performing a covert verb generation task. No significant interactions between illness and handedness and no illness effect were observed in functional asymmetry. There was significantly less leftward asymmetry of the inferior frontal, precentral, and supramarginal gyri as well as the intra-parietal sulcus in non-right-handers compared to right-handers taking into account the task performances. Our findings suggested that decreased lateralization for language production was more closely related to handedness than to schizophrenia.

FMRI Activation in Language Areas Correlates with Verb Generation Performance in Children

Functional MRI mapping of language areas in children frequently employs a covert verb generation task. Because responses are not monitored, the relationship between fMRI activation and task performance is unknown. We compared fMRI activation during covert and overt verb generation to performance during the overt task. 15 children, ages 11-13 years, listened to concrete nouns and responded with related verbs covertly and overtly. A clustered fMRI acquisition allowed for recording of overt responses without motion artifacts. Region of interest analysis was also performed in areas that exhibited correlation between activation and performance during overt verb generation in left inferior frontal and left superior temporal gyri (along with their right hemisphere homologues). Regression analysis determined that during both covert and overt generation, left hemisphere regions showed positive correlations with average counts of verbs generated during the overt task. These results suggest that increased verb generation performance leads to increased activation. In addition, overt performance may be used as an estimator of covert performance.

A group independent component analysis of covert verb generation in children: A functional magnetic resonance imaging study

Semantic language skills are an integral part of early childhood language development. The semantic association between verbs and nouns constitutes an important building block for the construction of sentences. In this large-scale functional magnetic resonance imaging (fMRI) study, involving 336 subjects between the ages of 5 and 18 years, we investigated the neural correlates of covert verb generation in children. Using group independent component analysis (ICA), seven task-related components were identified including the mid-superior temporal gyrus, the most posterior aspect of the superior temporal gyrus, the parahippocampal gyrus, the inferior frontal gyrus, the angular gyrus, and medial aspect of the parietal lobule (precuneus/posterior cingulate). A highly left-lateralized component was found including the medial temporal gyrus, the frontal gyrus, the inferior frontal gyrus, and the angular gyrus. The associated independent component (IC) time courses were analyzed to investigate developmental changes in the neural elements supporting covert verb generation. Observed age effects may either reflect specific local neuroplastic changes in the neural substrates supporting language or a more global transformation of neuroplasticity in the developing brain. The results are analyzed and presented in the framework of two theoretical models for neurocognitive brain development. In this context, group ICA of fMRI data from our large sample of children aged 5–18 years provides strong evidence in support of the regionally weighted model for cognitive neurodevelopment of language networks.

Neural substrate differences in language networks and associated language-related behavioral impairments in children with TBI: A preliminary fMRI investigation

The present study examined whether functional MRI (fMRI) can identify changes in the neural substrates of language in young children following traumatic brain injury (TBI). Eight children with TBI (F/M=3/5, age (Mean +/- SD)=7.98 +/- 1 years, range = 6-9 years) and a comparison group of nine children with orthopedic injuries (OI) (F/M=4/5, age (Mean +/- SD)=7.4 +/- 1 years, range=6-9 years) participated in an fMRI study of covert verb generation (VG). Results revealed significantly different BOLD signal activation in perisylvian language areas between the groups, after accounting for potential confounders such as verbal fluency and executive function. We also found significant associations between the BOLD signal activation and performance on language-specific neuropsychological tests (NEPSY verbal fluency score, Verbal IQ) and Glasgow Coma Scale (GCS) score. This study suggests that children with TBI have significantly different brain activation patterns in language circuitry compared to children with orthopedic injuries. Although we found clear differences in brain activation between the two groups, conventional MR images showed no evidence of structural abnormalities in five of eight children with TBI. Our study demonstrates the feasibility and potential utility of fMRI as a means of quantifying changes associated with language deficits in future pediatric TBI studies.

Language reorganization in children with early-onset lesions of the left hemisphere: an fMRI study.

It is widely assumed that following extensive damage to the left hemisphere sustained in early childhood, language functions are likely to reorganize and develop in the right hemisphere, especially if the lesion affects the classical Broca's or Wernicke's language areas. In the present study, functional MRI (fMRI) was used to examine language lateralization in 10 children and adolescents with intractable epilepsy who sustained an early lesion in the left hemisphere. Lesions were adjacent to or within anterior language cortex in five patients, while they were remote from both Broca's and Wernicke's areas in the remainder. A lateralization index was calculated on the basis of the number of voxels activated in the left and right inferior frontal gyri when performing a covert verb generation task. Only two patients were right-handed, suggesting a high incidence of functional reorganization for motor control in the remaining patients. Five out of 10 showed bilateral or right language lateralization, but lateralization could not be inferred from the proximity of lesions to classical language areas on an individual basis. Lesions in or near Broca's area were not associated with inter-hemispheric language reorganization in four out of five cases, but with perilesional activation within the damaged left hemisphere. Paradoxically, lesions remote from the classical language areas were associated with non-left language lateralization in four out of five cases. Finally, handedness, age at onset of chronic seizures, and site of EEG abnormality also showed no obvious association with language lateralization. In conclusion, it is difficult to infer intra- versus inter-hemispheric language reorganization on the basis of clinical observations in the presence of early pathology to the left hemisphere.

Influence of ANOVA Design and Anatomical Standardization on Statistical Mapping for PET Activation

We have created images ofzvalue, error, and variation components for a PET activation study using various ANOVA designs and anatomical standardization methods. Data were acquired in four PET centers. In each center, CBF was measured on six normal male subjects under resting and covert verb generation, three times for each. The images were anatomically standardized with LINEAR transformation, SPM (Ver. 95), HBA (Karolinska/Tohoku), or MICHIGAN (Minoshima). ANOVA was performed pixel by pixel to computet(andz) for the task main effect (Verb vs Rest) in four different designs: (i) two way (subject and task) (2W), (ii) two-way with interaction (2WI), (iii) subject considered a random factor (2WI-MX), and (iv) three-way (subject, task, and replication) (3W). A large area extending from the Broca to the left premotor cortex was activated. The localization of the highest peak depended both on the anatomical standardization and on the ANOVA design, the variation ranging 3–4 cm. Smoothing reduced the variation while erasing possible subfoci. Thezimages of 2W, 2WI, and 3W looked alike, whereas 2WI-MX presented lower peakzvalues. SPM tended to present higherzvalues than the other methods. The error was high in the gray and low in the white matter. The root mean square for the subject effect was high on the border of gray matter especially in LINEAR and HBA, revealing intersubject mismatch in the gray matter distribution. The root mean square for the subject-by-task interaction effect revealed individual variation in activation.