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During infancy and adolescence, language develops from a predominantly interhemispheric control--through the corpus callosum (CC)--to a predominantly intrahemispheric control, mainly subserved by the left arcuate fasciculus (AF). Using multimodal neuroimaging, we demonstrate that human left-handers (both male and female) with an atypical language lateralization show a rightward participation of language areas from the auditory cortex to the inferior frontal cortex when contrasting speech to tone perception and an enhanced interhemispheric anatomical and functional connectivity. Crucially, musicianship determines two different structural pathways to this outcome. Nonmusicians present a relation between atypical lateralization and intrahemispheric underdevelopment across the anterior AF, hinting at a dysregulation of the ontogenetic shift from an interhemispheric to an intrahemispheric brain. Musicians reveal an alternative pathway related to interhemispheric overdevelopment across the posterior CC and the auditory cortex. We discuss the heterogeneity in reaching atypical language lateralization and the relevance of early musical training in altering the normal development of language cognitive functions. [ABSTRACT FROM AUTHOR]

Background: In temporal lobe epilepsy (TLE), estimating the potential risk of language dysfunction before surgery is a necessary procedure. Functional MRI (fMRI) is considered the most useful to determine language lateralization noninvasively. However, there are no standardized language fMRI protocols, and several issues remain unresolved. In particular, the language tasks normally used are predominantly active paradigms that require the overt participation of patients, making assessment difficult for pediatric patients or patients with intellectual disabilities. In this study, task-based fMRI with passive narrative listening was applied to evaluate speech comprehension to estimate language function in Japanese-speaking patients with drug-resistant TLE. Methods: Twenty-one patients (six with intellectual disabilities) participated. Patients listened to passive auditory stimuli with combinations of forward and silent playback, and forward and backward playback. The activation results were extracted using a block design, and lateralization indices were calculated. The obtained fMRI results were compared to the results of the Wada test. Results: The concordance rate between fMRI and the Wada test was 95.2%. Meaningful responses were successfully obtained even from participants with intellectual disabilities. Conclusions: This passive fMRI paradigm can provide safe and easy presurgical language evaluation, particularly for individuals who may not readily engage in active paradigms. [ABSTRACT FROM AUTHOR]

Introduction: In addition to age-related changes in language, hemispheric lateralization of language functions steadily declines with age. Also, performance on word fluency tasks declines and is sensitive to the expression of dementia-related changes. The aim of this study is to evaluate the effect of anodal tDCS combined with a word fluency training on language lateralization and word fluency performance in healthy elderly subjects and in persons with mild cognitive impairment (MCI). Methods: The effect of anodal tDCS over the left inferio frontal gyrus (IFG) was measured in a group of healthy elderly up to the age of 67 years (YG, Ø = 63.9 ± 3.02), a group of healthy elderly aged 68 years and older (OG, Ø = 78.1, ± 4.85), and a group of patients with MCI (Ø = 81.18, ± 7.35) by comparing performance in phonological and semantic word fluency tasks before and after 3 days of tDCS. Half of the experimental participants received sham stimulation. In addition, language lateralization was determined using a lateralization index (LI) measured with functional transcranial Doppler sonography (fTCD) before and after the stimulation period. Results: Anodal tDCS was associated with significantly higher scores in phonological but not semantic word fluency in both YG and OG. In MCI patients, no difference was measured between the tDCS and sham groups in either word fluency task. fTCD showed significantly increased left lateralization in all three groups after the training phase. However, this effect was independent of tDCS and the degree of lateralization could not be predicted by word fluency performance in any of the groups. Discussion: Phonological word fluency can be increased with atDCS in healthy elderly people by stimulating the IFG in a 3-day training. When cognitive decline has reached a certain stage, as is the case with MCI, this paradigm does not seem to be effective enough. [ABSTRACT FROM AUTHOR]

Children with autism often show atypical brain lateralization for speech and language processing, however, it is unclear what linguistic component contributes to this phenomenon. Here we measured event-related potential (ERP) responses in 21 school-age autistic children and 25 age-matched neurotypical (NT) peers during listening to word-level prosodic stimuli. We found that both groups displayed larger late negative response (LNR) amplitude to native prosody than to nonnative prosody; however, unlike the NT group exhibiting left-lateralized LNR distinction of prosodic phonology, the autism group showed no evidence of LNR lateralization. Moreover, in both groups, the LNR effects were only present for prosodic phonology but not for phoneme-free prosodic acoustics. These results extended the findings of inadequate neural specialization for language in autism to sub-lexical prosodic structures. [ABSTRACT FROM AUTHOR]

Introduction: In addition to age-related changes in language, hemispheric lateralization of language functions steadily declines with age. Also, performance on word fluency tasks declines and is sensitive to the expression of dementia-related changes. The aim of this study is to evaluate the effect of anodal tDCS combined with a word fluency training on language lateralization and word fluency performance in healthy elderly subjects and in persons with mild cognitive impairment (MCI).Methods: The effect of anodal tDCS over the left inferio frontal gyrus (IFG) was measured in a group of healthy elderly up to the age of 67 years (YG, Ø = 63.9 ± 3.02), a group of healthy elderly aged 68 years and older (OG, Ø = 78.1, ± 4.85), and a group of patients with MCI (Ø = 81.18, ± 7.35) by comparing performance in phonological and semantic word fluency tasks before and after 3 days of tDCS. Half of the experimental participants received sham stimulation. In addition, language lateralization was determined using a lateralization index (LI) measured with functional transcranial Doppler sonography (fTCD) before and after the stimulation period.Results: Anodal tDCS was associated with significantly higher scores in phonological but not semantic word fluency in both YG and OG. In MCI patients, no difference was measured between the tDCS and sham groups in either word fluency task. fTCD showed significantly increased left lateralization in all three groups after the training phase. However, this effect was independent of tDCS and the degree of lateralization could not be predicted by word fluency performance in any of the groups.Discussion: Phonological word fluency can be increased with atDCS in healthy elderly people by stimulating the IFG in a 3-day training. When cognitive decline has reached a certain stage, as is the case with MCI, this paradigm does not seem to be effective enough.

The present study investigates a potential method of optimizing effective strategies for the functional lateralization of the dorsolateral prefrontal cortex (dlPFC) while in a scanner. Effective hemisphere lateralization of the dlPFC is crucial for lowering the functional risks connected to specific interventions (such as neurosurgery and transcranial magnetic stimulation (TMS), as well as increasing the effectiveness of a given intervention by figuring out the optimal location. This task combines elements of creative problem solving, executive decision making based on an internal rule set, and working memory. A retrospective analysis was performed on a total of 58 unique participants (34 males, 24 females, Mage = 42.93 years, SDage = 16.38). Of these participants, 47 were classified as right-handed, 7 were classified as left-handed, and 4 were classified as ambidextrous, according to the Edinburgh Handedness Inventory. The imaging data were qualitatively judged by two trained, blinded investigators (neurologist and neuropsychologist) for dominant handedness (primary motor cortex) and dominant dorsolateral prefrontal cortex (dlPFC). The results demonstrated that 21.4% of right-handed individuals showed a dominant dlPFC localized to the right hemisphere rather than the assumed left, and 16.7% of left-handers were dominant in their left hemisphere. The task completed in the scanner might be an efficient method for localizing a potential dlPFC target for the purpose of brain stimulation (e.g., TMS), though further study replications are needed to extend and validate these findings. [ABSTRACT FROM AUTHOR]

Background and Purpose: Resting‐state functional magnetic resonance imaging (rsfMRI) has been proposed as an alternative to task‐based fMRI including clinical situations such as preoperative brain tumor planning, due to advantages including ease of performance and time savings. However, one of its drawbacks is the limited ability to accurately lateralize language function. Methods: Using the rsfMRI data of healthy controls, we carried out a power spectra analysis on three regions of interest (ROIs): Broca's area (BA) in the frontal cortex for language, hand motor (HM) area in the primary motor cortex, and the primary visual cortex (V1). Spike removal, motion correction, linear trend removal, and spatial smoothing were applied. Spontaneous low‐frequency fluctuations (0.01‐0.1 Hz) were filtered to enable functional integration. Results: BA showed greater power on the left hemisphere relative to the right (p =.0055), while HM (p =.1563) and V1 (p =.4681) were not statistically significant. A novel index, termed the power laterality index (PLI), computed to estimate the degree of power lateralization for each brain region, revealed a statistically significant difference between BA and V1 (p <.00001), where V1 was used as a control since the primary visual cortex does not lateralize. Validation studies used to compare PLI to a laterality index computed using phonemic fluency, a task‐based, language fMRI paradigm, demonstrated good correlation. Conclusions: The power spectra for BA revealed left language lateralization, which was not replicated in HM or V1. This work demonstrates the feasibility and validity of an ROI‐based power spectra analysis on rsfMRI data for language lateralization. [ABSTRACT FROM AUTHOR]

Introduction: The single equivalent current dipole (sECD) is the standard clinical procedure for presurgical language mapping in epilepsy using magnetoencephalography (MEG). However, the sECD approach has not been widely used in clinical assessments, mainly because it requires subjective judgements in selecting several critical parameters. To address this limitation, we developed an automatic sECD algorithm (AsECDa) for language mapping. Methods: The localization accuracy of the AsECDa was evaluated using synthetic MEG data. Subsequently, the reliability and efficiency of AsECDa were compared to three other common source localization methods using MEG data recorded during two sessions of a receptive language task in 21 epilepsy patients. These methods include minimum norm estimation (MNE), dynamic statistical parametric mapping (dSPM), and dynamic imaging of coherent sources (DICS) beamformer. Results: For the synthetic single dipole MEG data with a typical signal-to-noise ratio, the average localization error of AsECDa was less than 2 mm for simulated superficial and deep dipoles. For the patient data, AsECDa showed better test-retest reliability (TRR) of the language laterality index (LI) than MNE, dSPM, and DICS beamformer. Specifically, the LI calculated with AsECDa revealed excellent TRR between the two MEG sessions across all patients (Cor = 0.80), while the LI for MNE, dSPM, DICSevent-related desynchronization (ERD) in the alpha band, and DICS-ERD in the low beta band ranged lower (Cor = 0.71, 0.64, 0.54, and 0.48, respectively). Furthermore, AsECDa identified 38% of patients with atypical language lateralization (i.e., right lateralization or bilateral), compared to 73%, 68%, 55%, and 50% identified by DICSERD in the low beta band, DICS-ERD in the alpha band, MNE, and dSPM, respectively. Compared to other methods, AsECDa's results were more consistent with previous studies that reported atypical language lateralization in 20-30% of epilepsy patients. Discussion: Our study suggests that AsECDa is a promising approach for presurgical language mapping, and its fully automated nature makes it easy to implement and reliable for clinical evaluations. [ABSTRACT FROM AUTHOR]

Previous research has shown a strong positive association between right‐handed gesturing and vocabulary development. However, the causal nature of this relationship remains unclear. In the current study, we tested whether gesturing with the right hand enhances linguistic processing in the left hemisphere, which is contralateral to the right hand. We manipulated the gesture hand children used in pointing tasks to test whether it would affect their performance. In either a linguistic task (verb learning) or a non‐linguistic control task (memory), 131 typically developing right‐handed 3‐year‐olds were encouraged to use either their right hand or left hand to respond. While encouraging children to use a specific hand to indicate their responses had no effect on memory performance, encouraging children to use the right hand to respond, compared to the left hand, significantly improved their verb learning performance. This study is the first to show that manipulating the hand with which children are encouraged to gesture gives them a linguistic advantage. Language lateralization in healthy right‐handed children typically involves a dominant left hemisphere. Producing right‐handed gestures may therefore lead to increased activation in the left hemisphere which may, in turn, facilitate forming and accessing lexical representations. It is important to note that this study manipulated gesture handedness among right‐handers and does therefore not support the practice of encouraging children to become right‐handed in manual activities. Research Highlights: Right‐handed 3‐year‐olds were instructed to point to indicate their answers exclusively with their right or left hand in either a memory or verb learning task.Right‐handed pointing was associated with improved verb generalization performance, but not improved memory performance.Thus, gesturing with the right hand, compared to the left hand, gives right‐handed 3‐year‐olds an advantage in a linguistic but not a non‐linguistic task.Right‐handed pointing might lead to increased activation in the left hemisphere and facilitate forming and accessing lexical representations. [ABSTRACT FROM AUTHOR]

IntroductionThe single equivalent current dipole (sECD) is the standard clinical procedure for presurgical language mapping in epilepsy using magnetoencephalography (MEG). However, the sECD approach has not been widely used in clinical assessments, mainly because it requires subjective judgements in selecting several critical parameters. To address this limitation, we developed an automatic sECD algorithm (AsECDa) for language mapping.MethodsThe localization accuracy of the AsECDa was evaluated using synthetic MEG data. Subsequently, the reliability and efficiency of AsECDa were compared to three other common source localization methods using MEG data recorded during two sessions of a receptive language task in 21 epilepsy patients. These methods include minimum norm estimation (MNE), dynamic statistical parametric mapping (dSPM), and dynamic imaging of coherent sources (DICS) beamformer.ResultsFor the synthetic single dipole MEG data with a typical signal-to-noise ratio, the average localization error of AsECDa was less than 2 mm for simulated superficial and deep dipoles. For the patient data, AsECDa showed better test-retest reliability (TRR) of the language laterality index (LI) than MNE, dSPM, and DICS beamformer. Specifically, the LI calculated with AsECDa revealed excellent TRR between the two MEG sessions across all patients (Cor = 0.80), while the LI for MNE, dSPM, DICS-event-related desynchronization (ERD) in the alpha band, and DICS-ERD in the low beta band ranged lower (Cor = 0.71, 0.64, 0.54, and 0.48, respectively). Furthermore, AsECDa identified 38% of patients with atypical language lateralization (i.e., right lateralization or bilateral), compared to 73%, 68%, 55%, and 50% identified by DICS-ERD in the low beta band, DICS-ERD in the alpha band, MNE, and dSPM, respectively. Compared to other methods, AsECDa’s results were more consistent with previous studies that reported atypical language lateralization in 20-30% of epilepsy patients.DiscussionOur study suggests that AsECDa is a promising approach for presurgical language mapping, and its fully automated nature makes it easy to implement and reliable for clinical evaluations.

fMRI language mapping studies report right-hemispheric contribution to language in healthy individuals. However, it remains unclear whether these right-hemispheric patterns of activity are critical for language, which is highly relevant for clinical preoperative language mapping. The available findings are controversial. In this study, we first measured individual patterns of language lateralization with an fMRI language localizer in healthy participants with different handedness (N = 31). Then, the same participants received rTMS over the individual coordinates of peak fMRI-based activation in the left and right inferior frontal gyri. During rTMS, participants performed a picture naming task. It included both objects and actions to test whether naming of nouns and verbs would be equally modulated by rTMS. Stimulation of the left inferior frontal gyrus resulted in accuracy facilitation of verb production regardless of individual language lateralization. No modulation of object naming was found at any stimulation site in terms of accuracy nor reaction time. This study causally confirmed the critical contribution of the left, but not the right hemisphere to verb production regardless of the language lateralization patterns observed with fMRI. Also, the results stress that action rather than object naming is the task of choice for mapping language in the frontal lobe. [ABSTRACT FROM AUTHOR]

The present study investigates a potential method of optimizing effective strategies for the functional lateralization of the dorsolateral prefrontal cortex (dlPFC) while in a scanner. Effective hemisphere lateralization of the dlPFC is crucial for lowering the functional risks connected to specific interventions (such as neurosurgery and transcranial magnetic stimulation (TMS), as well as increasing the effectiveness of a given intervention by figuring out the optimal location. This task combines elements of creative problem solving, executive decision making based on an internal rule set, and working memory. A retrospective analysis was performed on a total of 58 unique participants (34 males, 24 females, Mage = 42.93 years, SDage = 16.38). Of these participants, 47 were classified as right-handed, 7 were classified as left-handed, and 4 were classified as ambidextrous, according to the Edinburgh Handedness Inventory. The imaging data were qualitatively judged by two trained, blinded investigators (neurologist and neuropsychologist) for dominant handedness (primary motor cortex) and dominant dorsolateral prefrontal cortex (dlPFC). The results demonstrated that 21.4% of right-handed individuals showed a dominant dlPFC localized to the right hemisphere rather than the assumed left, and 16.7% of left-handers were dominant in their left hemisphere. The task completed in the scanner might be an efficient method for localizing a potential dlPFC target for the purpose of brain stimulation (e.g., TMS), though further study replications are needed to extend and validate these findings.

Objective: Atypical patterns of language lateralization due to early reorganizational processes constitute a challenge in the pre-surgical evaluation of patients with pharmaco-resistant epilepsy. There is no consensus on an optimal analysis method used for the identification of language dominance in MEG. This study examines the concordance between MEG source localization of beta power desynchronization and fMRI with regard to lateralization and localization of expressive and receptive language areas using a visual verb generation task.Methods: Twenty-five patients with pharmaco-resistant epilepsy, including six patients with atypical language lateralization, and ten right-handed controls obtained MEG and fMRI language assessment. Fourteen patients additionally underwent the Wada test. We analyzed MEG beta power desynchronization in sensor (controls) and source space (patients and controls). Beta power decrease between 13 and 35 Hz was localized applying Dynamic Imaging of Coherent Sources Beamformer technique. Statistical inferences were grounded on cluster-based permutation testing for single subjects.Results: Event-related desynchronization of beta power in MEG was seen within the language-dominant frontal and temporal lobe and within the premotor cortex. Our analysis pipeline consistently yielded left language dominance with high laterality indices in controls. Language lateralization in MEG and Wada test agreed in all 14 patients for inferior frontal, temporal and parietal language areas (Cohen’s Kappa = 1, p < 0.001). fMRI agreed with Wada test in 12 out of 14 cases (85.7%) for Broca’s area (Cohen’s Kappa = 0.71, p = 0.024), while the agreement for temporal and temporo-parietal language areas were non-significant. Concordance between MEG and fMRI laterality indices was highest within the inferior frontal gyrus, with an agreement in 19/24 cases (79.2%), and non-significant for Wernicke’s area. Spatial agreement between fMRI and MEG varied considerably between subjects and brain regions with the lowest Euclidean distances within the inferior frontal region of interest.Conclusion: Localizing the desynchronization of MEG beta power using a verb generation task is a promising tool for the identification of language dominance in the pre-surgical evaluation of epilepsy patients. The overall agreement between MEG and fMRI was lower than expected and might be attributed to differences within the baseline condition. A larger sample size and an adjustment of the experimental designs are needed to draw further conclusions.

Functional transcranial Doppler sonography (fTCD) is a time- and cost-effective, non-invasive approach to determining real time hemispheric lateralization and is well-suited for repetitive study designs comprising multiple days. To date, no study has examined the reproducibility of the direction and degree (strength) of lateralization during word fluency (WF) over multiple, consecutive sessions within a single person, although there are many studies of lateralization during language processing. Moreover, there is conflicting evidence as to whether there is a relationship between the degree of laterality and the word fluency performance. In this study, one right-handed male (aged 24 years) completed a total of seven examination sessions in the time span of 10 days. Each session comprised multiple phonological and semantic WF tasks. The maximum difference of relative cerebral blood flow velocity (CBFV) changes between the left and right middle cerebral artery (MCA) during WF was defined as the Lateralization Index (LI). The word-fluency performance and the LIs were used in a linear regression model to detect relative changes in the direction and degree of lateralization during repetitive WF tasks. The reproducibility of the direction of language-related lateralization is very stable over multiple sessions within this single person and the processed LIs were left-lateralized in every session for both WF tasks. In addition, performance during phonological WF could significantly predict the variability in the degree of lateralization. This result could not be confirmed for the semantic WF task. The results of this pilot study support the usage of fTCD as a reliable method for examining lateralization patterns, especially in longitudinal study designs. They also provide evidence for the notion that performance in WF tasks can be related to the degree of lateralization, at least intra-individually. [ABSTRACT FROM AUTHOR]

Even children with extensive perinatal left-sided lesions have been reported to show normal language functions based on right-hemispheric language reorganization. This reorganization can lead to deficits in originary right hemispheric functions ("crowding hypothesis"). In a previous study, however, we identified epilepsy (even when well-controlled), and not language reorganization, as the major risk factor for impaired nonverbal functions. Here, we asked whether verbal and nonverbal functions develop differently, and whether they share the same risk factors. We investigated 23 patients (11f, Md = 12.56 years) with perinatal strokes (16 left-sided, 8 with epilepsy), and 23 healthy age-matched controls (8 f, Md = 12.42years). Language functions were assessed using the Potsdam Illinois Test of Psycholinguistic Abilities, nonverbal intelligence with the Test of Nonverbal Intelligence, language lateralization with functional MRI, and lesion size with MRI-based volumetry. We found no systematic difference between verbal and nonverbal skills in our patients or controls [median difference Z(PITPA)-Z(TONI): patients = −0.03, controls = −0.06]. Accordingly, verbal and nonverbal functions were strongly correlated in patients (r = 0.80) and in controls (r = 0.74). Language ability correlated significantly with epilepsy. Furthermore, in patients with epilepsies, verbal skills were significantly lower than in controls. In our cohort, we found no evidence for a differential effect of perinatal strokes on the development of verbal versus nonverbal functions, and, specifically, no evidence for a preferential sparing of verbal functions. Epilepsy, even when well-controlled, was confirmed as a single key risk factor for verbal functions. • Prospective study on the cognitive development of verbal and nonverbal functions after perinatal strokes. • In our cohort, we found no evidence for a differential effect of perinatal strokes on the development of verbal versus nonverbal functions. • Epilepsy, even when well-controlled, is a key risk factor for impaired language functions. [ABSTRACT FROM AUTHOR]

Objective: The Wada test is used to evaluate language lateralization and memory performance after inactivation of an isolated cerebral hemisphere. Methohexital a short-acting barbiturate has a history of use to induce interictal discharges during intraoperative corticography. We report a new finding of activation of lateralized periodic discharges (LPDs) after Methohexital injection. Methods: We retrospectively reviewed 174 consecutive adult patients who underwent Wada testing in preparation for epilepsy surgery (N = 129, 74%) or brain tumor resection (N = 45, 26%) at the University of Michigan to determine the frequency of induced periodic discharges by methohexital. Results: Four epilepsy patients (2.29%) had methohexital-induced LPDs within a median of 2 s (1–99 s) of the injection and lasting a median of 4 min (3–10 min) after a total of 7 injections. All LPDs occurred ipsilateral to the injection hemisphere in the known region of interictal epileptiform discharges. LPDs were not induced in brain tumor patients. In one patient, LPDs occurred during memory testing, and this patient's memory performance was below expectation based on pre-test neuropsychological testing. Conclusions: Methohexital can induce LPDs in ipsilateral hemisphere and that can potentially affect memory performance. Significance: This observation indicates that concurrent EEG monitoring during the Wada test is important and that induced discharges should be considered when interpreting Wada test results.

Previous studies have shown a link between language abilities and right hand preference (RHP) for both object manipulation and pointing between 10 and 18 months of age. For infants, RHP can still be unstable. The purpose of the present study was to test whether the link between vocabulary and RHP exists among 9‐month‐old infants. The study included 88 infants who were observed in videotaped free‐play interactions with their mothers at 9 months of age. The infants' hand preference was coded for touching objects and pointing. The children's vocabulary was measured at 9, 12, and 18 months of age. The results showed a small and significant RHP for touching objects and no significant RHP for pointing. The degree of RHP was not correlated with vocabulary scores at any age. One interpretation of these results is that, for the infants in this study, the lateralization for motor abilities was still stabilizing and therefore showed no relationship with their vocabulary. If so, this result is consistent with the argument that language lateralization builds on the lateralization for skilled and/or communicative movement. [ABSTRACT FROM AUTHOR]

A previous study we reported in this journal suggested that left and right-handers may differ in their patterns of lateralization for different language tasks (Woodhead et al. 2019 R. Soc. Open Sci. 6, 181801. (doi:10.1098/rsos.181801)). However, it had too few left-handers (N = 7) to reach firm conclusions. For this update paper, further participants were added to the sample to create separate groups of left- (N = 31) and right-handers (N = 43). Two hypotheses were tested: (1) that lateralization would be weaker at the group level in left-than right-handers; and (2) that left-handers would show weaker covariance in lateralization between tasks, supporting a two-factor model. All participants performed the same protocol as in our previous paper: lateralization was measured using functional transcranial Doppler sonography during six different language tasks, on two separate testing sessions. The results supported hypothesis 1, with significant differences in laterality between groups for four out of six tasks. For hypothesis 2, structural equation modelling showed that there was stronger evidence for a two-factor model in left than right-handers; furthermore, examination of the factor loadings suggested that the pattern of laterality across tasks may also differ between handedness groups. These results expand on what is known about the differences in laterality between left- and right-handers.

Functional transcranial Doppler sonography (fTCD) is a time- and cost-effective, non-invasive approach to determining real time hemispheric lateralization and is well-suited for repetitive study designs comprising multiple days. To date, no study has examined the reproducibility of the direction and degree (strength) of lateralization during word fluency (WF) over multiple, consecutive sessions within a single person, although there are many studies of lateralization during language processing. Moreover, there is conflicting evidence as to whether there is a relationship between the degree of laterality and the word fluency performance. In this study, one right-handed male (aged 24 years) completed a total of seven examination sessions in the time span of 10 days. Each session comprised multiple phonological and semantic WF tasks. The maximum difference of relative cerebral blood flow velocity (CBFV) changes between the left and right middle cerebral artery (MCA) during WF was defined as the Lateralization Index (LI). The word-fluency performance and the LIs were used in a linear regression model to detect relative changes in the direction and degree of lateralization during repetitive WF tasks. The reproducibility of the direction of language-related lateralization is very stable over multiple sessions within this single person and the processed LIs were left-lateralized in every session for both WF tasks. In addition, performance during phonological WF could significantly predict the variability in the degree of lateralization. This result could not be confirmed for the semantic WF task. The results of this pilot study support the usage of fTCD as a reliable method for examining lateralization patterns, especially in longitudinal study designs. They also provide evidence for the notion that performance in WF tasks can be related to the degree of lateralization, at least intra-individually.

Understanding the processes underlying normal, impaired, and recovered language performance has been a long-standing goal for cognitive and clinical neuroscience. Many verbally described hypotheses about language lateralization and recovery have been generated. However, they have not been considered within a single, unified, and implemented computational framework, and the literatures on healthy participants and patients are largely separated. These investigations also span different types of data, including behavioral results and functional MRI brain activations, which augment the challenge for any unified theory. Consequently, many key issues, apparent contradictions, and puzzles remain to be solved. We developed a neurocomputational, bilateral pathway model of spoken language production, designed to provide a unified framework to simulate different types of data fromhealthy participants and aphasic patients. The model encapsulates key computational principles (differential computational capacity, emergent division of labor across pathways, experience-dependent plasticityrelated recovery) and provides an explanation for the bilateral yet asymmetric lateralization of language in healthy participants, chronic aphasia after left rather than right hemisphere lesions, and the basis of partial recovery in patients. The model provides a formal basis for understanding the relationship between behavioral performance and brain activation. The unified model is consistent with the degeneracy and variable neurodisplacement theories of language recovery, and adds computational insights to these hypotheses regarding the neural machinery underlying language processing and plasticityrelated recovery following damage. [ABSTRACT FROM AUTHOR]

Purpose: To validate four established, child-friendly functional magnetic resonance imaging (fMRI) language tasks (word chain task [WCT], vowel identification task [VIT], synonym task [SYT] and beep story task [BST]) in a predominantly pediatric cohort. Methods: Intracarotid amobarbital procedures (IAP) (n = 17) and unchanged language after hemispherotomy (n = 6) were used as gold standards. The fMRI activations of nine regions of interest (ROI) in the frontal, temporal and parietal lobes as well as in the cerebellum were visually assessed in 23 fMRI examinations (in total 117 fMRI task sessions) of 23 patients (age range 10.0–23.0 years) with drug-refractory epilepsies. Results: The ROIs were considered valid when they showed activation in more than 25% of all sessions for the respective task and never showed false lateralization (in comparison to gold standards). Thus, 13 valid, task-specific ROIs were identified: 5 ROIs for the WCT (frontal operculum, inferior frontal gyrus, middle frontal gyrus, intraparietal sulcus, cerebellum), 3 ROIs for the VIT (frontal operculum, inferior frontal gyrus, middle frontal gyrus), 3 ROIs for the SYT (frontal operculum, inferior frontal gyrus, temporal language area) and 2 ROIs for the BST (inferior frontal gyrus, middle frontal gyrus). Conclusion: Clinical fMRI using the battery of four tasks is a valid tool for lateralizing language in children, adolescents and young adults. Each task proved to be specifically useful, which confirms that applying different tasks increases the probability of diagnosing language dominance in presurgical candidates. [ABSTRACT FROM AUTHOR]

Recent neurophysiological theories propose that the cerebral hemispheres collaborate to resolve the complex temporal nature of speech, such that left‐hemisphere (or bilateral) gamma‐band oscillatory activity would specialize in coding information at fast rates (phonemic information), whereas right‐hemisphere delta‐ and theta‐band activity would code for speech's slow temporal components (syllabic and prosodic information). Despite the relevance that neural entrainment to speech might have for reading acquisition and for core speech perception operations such as the perception of intelligible speech, no study had yet explored its development in young children. In the current study, speech‐brain entrainment was recorded via EEG in a cohort of children at three different time points since they were 4–5 to 6–7 years of age. Our results showed that speech‐brain entrainment occurred only at delta frequencies (0.5 Hz) at all testing times. The fact that, from the longitudinal perspective, coherence increased in bilateral temporal electrodes suggests that, contrary to previous hypotheses claiming for an innate right‐hemispheric bias for processing prosodic information, at 7 years of age the low‐frequency components of speech are processed in a bilateral manner. Lastly, delta speech‐brain entrainment in the right hemisphere was related to an indirect measure of intelligibility, providing preliminary evidence that the entrainment phenomenon might support core linguistic operations since early childhood. [ABSTRACT FROM AUTHOR]

Magnetoencephalographic imaging (MEGI) offers a non-invasive alternative for defining preoperative language lateralization in neurosurgery patients. MEGI indeed can be used for accurate estimation of language lateralization with a complex language task – auditory verb generation. However, since language function may vary considerably in patients with focal lesions, it is important to optimize MEGI for estimation of language function with other simpler language tasks. The goal of this study was to optimize MEGI laterality analyses for two such simpler language tasks that can have compliance from those with impaired language function: a non-word repetition (NWR) task and a picture naming (PN) task. Language lateralization results for these two tasks were compared to the verb-generation (VG) task. MEGI reconstruction parameters (regions and time windows) for NWR and PN were first defined in a presurgical training cohort by benchmarking these against laterality indices for VG. Optimized time windows and regions of interest (ROIs) for NWR and PN were determined by examining oscillations in the beta band (12–30 Hz) a marker of neural activity known to be concordant with the VG laterality index (LI). For NWR, additional ROIs include areas MTG/ITG and for both NWR and PN, the postcentral gyrus was included in analyses. Optimal time windows for NWR were defined as 650–850 ms (stimulus-locked) and −350 to −150 ms (response-locked) and for PN −450 to −250 ms (response-locked). To verify the optimal parameters defined in our training cohort for NWR and PN, we examined an independent validation cohort (n = 30 for NWR, n = 28 for PN) and found high concordance between VG laterality and PN laterality (82%) and between VG laterality and NWR laterality (87%). Finally, in a test cohort (n = 8) that underwent both the intracarotid amobarbital procedure (IAP) test and MEG for VG, NWR, and PN, we identified excellent concordance (100%) with IAP for VG + NWR + PN composite LI, high concordance for PN alone (87.5%), and moderate concordance for NWR alone (66.7%). These findings provide task options for non-invasive language mapping with MEGI that can be calibrated for language abilities of individual patients. Results also demonstrate that more accurate estimates can be obtained by combining laterality estimates obtained from multiple tasks. MEGI

Background: FMRI is a noninvasive tool for mapping language networks, especially in children. We conducted FMRI studies in children in the age group 8- 12 years using 2 different paradigms for assessing language networks and lateralization. Aim: To map language networks in pre-adolescent children and to calculate lateralization index using two different visual paradigms. Methods and Materials: The study was conducted in normal right handed children in the age group 8-12 years. Sixteen normal subjects underwent FMRI using 2 paradigms- visual verb generation (VVG), word pairs paradigm (WPP) to stimulate language areas. FMRI data analysis was done using SPM8 (statistical parametric Mapping) software. Total activated voxels were calculated for each hemispheres in the pre-defined ROIs for both paradigms. Results: FMRI showed left language lateralization in 13 out of 16 children with both VVG and WPP and bilateral language lateralization in two subjects. With VVG there was more significant activation in the left inferior triangular gyrus (ITG) (P < 0.001), left inferior opercular gyrus (IOG) (P < 0.01), left middle frontal gyrus (MFG) (P < 0.05), left and right dorsolateral prefrontal cortex (P < 0.05). Left posterior superior temporal gyrus (STG or WA) (P < 0.001), Left AG (P < 0.03), Left SMG (P < 0.05) were significantly activated with WP paradigm. Conclusion: Our FMRI studies showed that VGP predominantly activated frontal language areas and WPP predominantly activated temperoparietal language areas. Several other brain regions were also involved in language processing apart from the classical language areas.

Magnetoencephalographic imaging (MEGI) offers a non-invasive alternative for defining preoperative language lateralization in neurosurgery patients. MEGI indeed can be used for accurate estimation of language lateralization with a complex language task – auditory verb generation. However, since language function may vary considerably in patients with focal lesions, it is important to optimize MEGI for estimation of language function with other simpler language tasks. The goal of this study was to optimize MEGI laterality analyses for two such simpler language tasks that can have compliance from those with impaired language function: a non-word repetition (NWR) task and a picture naming (PN) task. Language lateralization results for these two tasks were compared to the verb-generation (VG) task. MEGI reconstruction parameters (regions and time windows) for NWR and PN were first defined in a presurgical training cohort by benchmarking these against laterality indices for VG. Optimized time windows and regions of interest (ROIs) for NWR and PN were determined by examining oscillations in the beta band (12–30 Hz) a marker of neural activity known to be concordant with the VG laterality index (LI). For NWR, additional ROIs include areas MTG/ITG and for both NWR and PN, the postcentral gyrus was included in analyses. Optimal time windows for NWR were defined as 650–850 ms (stimulus-locked) and −350 to −150 ms (response-locked) and for PN −450 to −250 ms (response-locked). To verify the optimal parameters defined in our training cohort for NWR and PN, we examined an independent validation cohort (n = 30 for NWR, n = 28 for PN) and found high concordance between VG laterality and PN laterality (82%) and between VG laterality and NWR laterality (87%). Finally, in a test cohort (n = 8) that underwent both the intracarotid amobarbital procedure (IAP) test and MEG for VG, NWR, and PN, we identified excellent concordance (100%) with IAP for VG + NWR + PN composite LI, high concordance for PN alone (87.5%), and moderate concordance for NWR alone (66.7%). These findings provide task options for non-invasive language mapping with MEGI that can be calibrated for language abilities of individual patients. Results also demonstrate that more accurate estimates can be obtained by combining laterality estimates obtained from multiple tasks. MEGI [ABSTRACT FROM AUTHOR]

The brain is one of the most prominent examples for structural and functional differences between the left and right half of the body. For handedness and language lateralization, the most widely investigated behavioral phenotypes, only a small fraction of phenotypic variance has been explained by molecular genetic studies. Due to environmental factors presumably also playing a role in their ontogenesis and based on first molecular evidence, it has been suggested that functional hemispheric asymmetries are partly under epigenetic control. This review article aims to elucidate the molecular factors underlying hemispheric asymmetries and their association with inner organ asymmetries. While we previously suggested that epigenetic mechanisms might partly account for the missing heritability of handedness, this article extends this idea by suggesting possible alternatives for transgenerational transmission of epigenetic states that do not require germ line epigenetic transmission. This is in line with a multifactorial model of hemispheric asymmetries, integrating genetic, environmental, and epigenetic influencing factors in their ontogenesis.

Hemispheric dominance for language can vary from task to task, but it is unclear if this reflects error of measurement or independent lateralization of different language systems. We used functional transcranial Doppler sonography to assess language lateralization within the middle cerebral artery territory in 37 adults (seven left-handers) on six tasks, each given on two occasions. Tasks taxed different aspects of language function. A pre-registered structural equation analysis was used to compare models of means and covariances. For most people, a single lateralized factor explained most of the covariance between tasks. A minority, however, showed dissociation of asymmetry, giving a second factor. This was mostly derived from a receptive task, which was highly reliable but not lateralized. The results suggest that variation in the strength of language lateralization reflects true individual differences and not just error of measurement. The inclusion of several tasks in a laterality battery makes it easier to detect cases of atypical asymmetry.

Children born preterm are at risk of impairments in oromotor control, with implications for early feeding and speech development. In this study, we aimed to identify (a) neuroanatomical markers of persistent oromotor deficits using diffusion-weighted imaging (DWI) tractography and (b) evidence of compensatory neuroplasticity using functional MRI (fMRI) during a language production task. In a cross-sectional study of 36 adolescents born very preterm (

Purpose: Our aim is to investigate whether rs-fMRI can be used as an effective technique to study language lateralization. We aim to find out the most appropriate language network among different networks identified using ICA. Methods: Fifteen healthy right-handed subjects, sixteen left, and sixteen right temporal lobe epilepsy patients prospectively underwent MR scanning in 3T MRI (GE Discovery™ MR750w), using optimized imaging protocol. We obtained task-fMRI data using a visual-verb generation paradigm. Rs-fMRI and language-fMRI analysis were conducted using FSL software. Independent component analysis (ICA) was used to estimate rs-fMRI networks. Dice coefficient was calculated to examine the similarity in activated voxels of a common language template and the rs-fMRI language networks. Laterality index (LI) was calculated from the task-based language activation and rs-fMRI language network, for a range of LI thresholds at different z scores. Results: Measurement of hemispheric language dominance with rs-fMRI was highly concordant with task-fMRI results. Among the evaluated z scores for a range of LI thresholds, rs-fMRI yielded a maximum accuracy of 95%, a sensitivity of 83%, and specificity of 92.8% for z = 2 at 0.05 LI threshold. Conclusion: The present study suggests that rs-fMRI networks obtained using ICA technique can be used as an alternative for task-fMRI language laterality. The novel aspect of the work is suggestive of optimal thresholds while applying rs-fMRI, is an important endeavor given that many patients with epilepsy have co-morbid cognitive deficits. Thus, an accurate method to determine language laterality without requiring a patient to complete the language task would be advantageous. [ABSTRACT FROM AUTHOR]

Establishing language dominance is an important step in the presurgical evaluation of patients with refractory epilepsy. In the absence of a universally accepted gold-standard non-invasive method to determine language dominance in the preoperative assessment, a range of tools and methodologies have recently received attention. When applied to pediatric age, many of the proposed methods, such as functional magnetic resonance imaging (fMRI), may present some challenges due to the time-varying effects of epileptogenic lesions and of on-going seizures on maturational phenomena. Magnetoencephalography (MEG) has the advantage of being insensitive to the distortive effects of anatomical lesions on brain microvasculature and to differences in the metabolism or vascularization of the developing brain and also provides a less intimidating recording environment for younger children. In this study we investigated the reliability of lateralized synchronous cortical activation during a verb generation task in a group of 28 children (10 males and 18 females, mean age 12 years) with refractory epilepsy who were evaluated for epilepsy surgery. The verb generation task was associated with significant decreases in beta oscillatory power (13–30 Hz) in frontal and temporal lobes. The MEG data were compared with other available presurgical non-invasive data including cortical stimulation, neuropsychological and fMRI data on language lateralization where available. We found that the lateralization of MEG beta power reduction was concordant with language dominance determined by one or more different assessment methods (i.e. cortical stimulation mapping, neuropsychological, fMRI or post-operative data) in 89% of patients. Our data suggest that qualitative hemispheric differences in task-related changes of spectral power could offer a promising insight into the contribution of dominant and non-dominant hemispheres in language processing and may help to characterize the specialization and lateralization of language processes in children. [ABSTRACT FROM AUTHOR]

The brain is one of the most prominent examples for structural and functional differences between the left and right half of the body. For handedness and language lateralization, the most widely investigated behavioral phenotypes, only a small fraction of phenotypic variance has been explained by molecular genetic studies. Due to environmental factors presumably also playing a role in their ontogenesis and based on first molecular evidence, it has been suggested that functional hemispheric asymmetries are partly under epigenetic control. This review article aims to elucidate the molecular factors underlying hemispheric asymmetries and their association with inner organ asymmetries. While we previously suggested that epigenetic mechanisms might partly account for the missing heritability of handedness, this article extends this idea by suggesting possible alternatives for transgenerational transmission of epigenetic states that do not require germ line epigenetic transmission. This is in line with a multifactorial model of hemispheric asymmetries, integrating genetic, environmental, and epigenetic influencing factors in their ontogenesis. [ABSTRACT FROM AUTHOR]

The ability to speak is a unique human capacity, but where is it located in our brains? This question is closely connected to the pioneering work of Pierre Paul Broca in the 1860s. Based on post-mortem observations of aphasic patients' brains, Broca located language production in the 3rd convolution of the left frontal lobe and thus reinitiated the localizationist view of brain functions. However, contemporary neuroscience has partially rejected this view in favor of a network-based perspective. This leads to the question, whether Broca's findings are still relevant today. In this mini-review, we discuss current and historical implications of Broca's work by focusing on his original contribution and contrasting it with contemporary knowledge. Borrowing from Broca's famous quote, our review shows that humans indeed "speak with the left hemisphere"- but Broca's area is not the sole "seat of articulatory language". [ABSTRACT FROM AUTHOR]

In patients with gliomas, changes in hemispheric specialization for language determined by magnetoencephalography (MEG) were analyzed to elucidate the impact of treatment and tumor recurrence on language networks. Demonstration of reorganization of language networks in these patients has significant implications on the prevention of postoperative functional loss and recovery. Whole‐brain activity during an auditory verb generation task was estimated from MEG recordings in a group of 73 patients with recurrent gliomas. Hemisphere of language dominance was estimated using the language laterality index (LI), a measure derived from the task. The initial scan was performed prior to resection; patients subsequently underwent surgery and adjuvant treatment. A second scan was performed upon recurrence prior to repeat resection. The relationship between the shift in LI between scans and demographics, anatomic location, pathology, and adjuvant treatment was analyzed. Laterality shifts were observed between scans; the median percent change was 29.1% across all patients. Laterality shift magnitude and relative direction were associated with the initial position of language dominance; patients with increased lateralization experienced greater shifts than those presenting more bilateral representation. A change in LI from left or right to bilateral (or vice versa) occurred in 23.3% of patients; complete switch occurred in 5.5% of patients. Patients with tumors within the language‐dominant hemisphere experienced significantly greater shifts than those with contralateral tumors. The majority of patients with glioma experience shifts in language network organization over time which correlate with the relative position of language lateralization and tumor location. [ABSTRACT FROM AUTHOR]

Children born preterm are at risk of impairments in oromotor control, with implications for early feeding and speech development. In this study, we aimed to identify (a) neuroanatomical markers of persistent oromotor deficits using diffusion-weighted imaging (DWI) tractography and (b) evidence of compensatory neuroplasticity using functional MRI (fMRI) during a language production task. In a cross-sectional study of 36 adolescents born very preterm (<33 weeks' gestation) we identified persistent difficulties in oromotor control in 31% of cases, but no clinical diagnoses of speech-sound disorder (e.g., dysarthria, dyspraxia). We used DWI-tractography to examine the microstructure (fractional anisotropy, FA) of the corticospinal and corticobulbar tracts. Compared to the unimpaired group, the oromotor-impaired group showed (i) reduced FA within the dorsal portion of the left corticobulbar tract (containing fibres associated with movements of the lips, tongue, and larynx) and (ii) greater recruitment of right hemisphere language regions on fMRI. We conclude that, despite the development of apparently normal everyday speech, early injury to the corticobulbar tract leads to persistent subclinical problems with voluntary control of the face, lips, jaw, and tongue. Furthermore, we speculate that early speech problems may be ameliorated by cerebral plasticity – in particular, recruitment of right hemisphere language areas. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of statistical thresholding and to determine an optimal functional magnetic resonance imaging [fMRI] statistical threshold for Thai language lateralization. Materials and Methods: The present study was prospective descriptive study of twenty Thai native speaker right-handed healthy volunteers performed Thai verb and word generation paradigms during 3T fMRI. Bihemispheric activation difference of language region of interests was calculated for laterality index [LI] through ranks of statistical threshold, from the threshold that generated an empty map to the minimal threshold with p-value less than 0.05. Results: LI of both verb generation and word generation paradigms tended to rise in higher statistical thresholds. In two subjects, shifted of LI from co-dominant to left dominant were found as an effect of statistical thresholding on both paradigms. A threshold (t-value) of 7 in verb generation paradigm and a threshold (t-value) of 6 in word generation paradigm significantly increased mean LI (with p-value 0.004 and 0.003, respectively) and categorized 95% of the subjects as left hemispheric dominance. Conclusion: LI varies across different statistical thresholds. Optimal thresholds (t-value) for language lateralization are 7 in Thai verb generation and 6 in Thai word generation paradigms. [ABSTRACT FROM AUTHOR]

Pre-operative assessment of language localization and lateralization is critical to preserving brain function after lesion or epileptogenic tissue resection. Task fMRI (t-fMRI) has been extensively and reliably used to this end, but resting state fMRI (rs-fMRI) is emerging as an alternative pre-operative brain mapping method that is independent of a patient's ability to comply with a task. We sought to evaluate if language lateralization obtained from rs-fMRI can replace standard assessment using t-fMRI. In a group of 43 patients scheduled for pre-operative fMRI brain mapping and 17 healthy controls, we found that existing methods of determining rs-fMRI lateralization by considering interhemispheric and intrahemispheric functional connectivity are inadequate compared to t-fMRI when applied to the language network. We determined that this was attributable to widespread but nuanced disturbances in the functional connectivity of the language network in patients. We found changes in interhemispheric and intrahemispheric functional connectivity that were dependent on lesion location, and particularly impacted patients with lesions in the left temporal lobe. We then tested whether a simpler measure of functional connectivity to the language network has a better relation to t-fMRI based language lateralization. Remarkably, we found that functional connectivity between the language network and the frontal pole, and superior frontal gyrus, as well as the supramarginal gyrus, significantly correlated to task based language lateralization indices in both patients and healthy controls. These findings are consistent with prior work with epilepsy patients, and provide a framework for evaluating language lateralization at rest.

Objectives: Impaired attention and language functions are common in psychosis, but have been less explored in subjects with ultra-high risk for psychosis (UHR). The aim of the study was to investigate differences in language lateralization and auditory attention in UHR subjects compared to healthy controls with a dichotic listening paradigm. In addition, symptoms from The Structural Interview for Prodromal Syndromes (SIPS) were explored in relation to performance on dichotic listening.Methods: The UHR subjects (n = 46, female = 28, mean age = 17.9) were compared to a group of healthy controls (n = 40, female = 20, mean age = 16.8). A split-plot repeated measures analysis of covariance was conducted with group as between-subjects factor and attention conditions (non-forced, forced-right, forced-left) and side (right ear, left ear) as repeated measures factors (2×3×2 design) using gender, age and handedness as covariates. SIPS symptoms were subjected to Spearman’s r correlations with laterality indexes and attentional gain in each ear.Results: There was a statistically significant three-way interaction of group (UHR, healthy controls) × forced condition (non-forced, forced-right, forced-left) × side (right ear, left ear), p = 0.048. The effect was due to an interaction between group × side in the forced-left condition. There were no significant differences between UHR subjects and healthy controls in the non-forced condition. Right ear gain correlated with “Perceptual abnormalities/Hallucinations” (P4), r = 0.486, p = 0.001.Conclusion: UHR subjects demonstrated impairment in top-down attentional mechanisms, but showed no language lateralization abnormalities. Impairment in top-down attentional mechanisms are frequently reported from dichotic listening studies in patients with schizophrenia. Higher levels of perceptual abnormalities and hallucinatory experiences were associated with enhanced report from the right ear in the forced-right condition.

Objective: The aim of this study was to evaluate the clinical use of a method to assess hemispheric language dominance in pediatric candidates for epilepsy surgery. The method is designed for patients but has previously been evaluated with healthy children. Methods: Nineteen patients, 8–18 years old, with intractable epilepsy and candidates for epilepsy surgery were assessed. The assessment consisted of two functional MRI protocols (fMRI) intended to target frontal and posterior language networks respectively, and a behavioral dichotic listening task (DL). Regional left/right indices for each fMRI task from the frontal, temporal and parietal lobe were calculated, and left/right indices of the DL task were calculated from responses of consonants and vowels, separately. A quantitative analysis of each patient's data set was done in two steps based on clearly specified criteria. First, fMRI data and DL data were analyzed separately to determine whether the result from each of these assessments were conclusive or not. Thereafter, the results from the individual assessments were combined to reach a final conclusion regarding hemispheric language dominance. Results: For 14 of the 19 subjects (74%) a conclusion was reached about their hemispheric language dominance. Nine subjects had a left-sided and five subjects had a right-sided hemispheric dominance. In three cases (16%) DL provided critical data to reach a conclusive result. Conclusions: The success rate of conclusive language lateralization assessments in this study is comparable to reported rates on similar challenged pediatric populations. The results are promising but data from more patients than in the present study will be required to conclude on the clinical applicability of the method.

Abstract: Determining the anatomical basis of hemispheric language dominance (HLD) remains an important scientific endeavor. The Wada test remains the gold standard test for HLD and provides a unique opportunity to determine the relationship between HLD and hemispheric structural asymmetries on MRI. In this study, we applied a whole‐brain voxel‐based asymmetry (VBA) approach to determine the relationship between interhemispheric structural asymmetries and HLD in a large consecutive sample of Wada tested patients. Of 135 patients, 114 (84.4%) had left HLD, 10 (7.4%) right HLD, and 11 (8.2%) bilateral language representation. Fifty‐four controls were also studied. Right‐handed controls and right‐handed patients with left HLD had comparable structural brain asymmetries in cortical, subcortical, and cerebellar regions that have previously been documented in healthy people. However, these patients and controls differed in structural asymmetry of the mesial temporal lobe and a circumscribed region in the superior temporal gyrus, suggesting that only asymmetries of these regions were due to brain alterations caused by epilepsy. Additional comparisons between patients with left and right HLD, matched for type and location of epilepsy, revealed that structural asymmetries of insula, pars triangularis, inferior temporal gyrus, orbitofrontal cortex, ventral temporo‐occipital cortex, mesial somatosensory cortex, and mesial cerebellum were significantly associated with the side of HLD. Patients with right HLD and bilateral language representation were significantly less right‐handed. These results suggest that structural asymmetries of an insular‐fronto‐temporal network may be related to HLD. [ABSTRACT FROM AUTHOR]

We investigated the association between the left planum temporale (PT) surface area or asymmetry and the hemispheric or regional functional asymmetries during language production and perception tasks in 287 healthy adults (BIL&GIN) who were matched for sex and handedness. The measurements of the PT surface area were performed after manually delineating the region using brain magnetic resonance images (MRI) and considering the Heschl’s gyrus (HG) duplication pattern; the measurements either included (PTtot) or did not include (PTpost) the second gyrus. A region encompassing both the PT and HG (HGPT) was also studied. Regardless of the ROI measured, 80% of the sample had a positive left minus right PT asymmetry. We first tested whether the PTtot, PTpost and HGPT surface areas in the left or right hemispheres or PT asymmetries differed in groups of individuals varying in language lateralization by assessing their hemispheric index during a sentence production minus word list production task. We then investigated the association between these different measures of the PT anatomy and the regional asymmetries measured during the task. Regardless of the anatomical definition used, we observed no correlations between the left surface areas or asymmetries and the hemispheric or regional functional asymmetries during the language production task. We then performed a similar analysis using the same sample measuring language functional lateralization during speech listening tasks (i.e., listening to sentences and lists of words). Although the hemispheric lateralization during speech listening was not correlated with the left PTtot, PTpost or HGPT surface areas or the PT asymmetries, significant positive correlations were observed between the asymmetries in these regions and the regional functional asymmetries measured in areas adjacent to the end of the Sylvian fissure while participants listened to the word lists or sentences. The PT asymmetry thus appears to be associated with the local functional asymmetries in auditory areas but is not a marker of inter-individual variability in language dominance. [ABSTRACT FROM AUTHOR]

Background: FMRI is a noninvasive tool for mapping language networks, especially in children. We conducted FMRI studies in children in the age group 8-12 years using 2 different paradigms for assessing language networks and lateralization. Aim: To map language networks in pre-adolescent children and to calculate lateralization index using two different visual paradigms. Methods and Materials: The study was conducted in normal right handed children in the age group 8-12 years. Sixteen normal subjects underwent FMRI using 2 paradigms- visual verb generation (VVG), word pairs paradigm (WPP) to stimulate language areas. FMRI data analysis was done using SPM8 (statistical parametric Mapping) software. Total activated voxels were calculated for each hemispheres in the pre-defined ROIs for both paradigms. Results: FMRI showed left language lateralization in 13 out of 16 children with both VVG and WPP and bilateral language lateralization in two subjects. With VVG there was more significant activation in the left inferior triangular gyrus (ITG) (P < 0.001), left inferior opercular gyrus (IOG) (P < 0.01), left middle frontal gyrus (MFG) (P < 0.05), left and right dorsolateral prefrontal cortex (P < 0.05). Left posterior superior temporal gyrus (STG or WA) (P < 0.001), Left AG (P < 0.03), Left SMG (P < 0.05) were significantly activated with WP paradigm. Conclusion: Our FMRI studies showed that VGP predominantly activated frontal language areas and WPP predominantly activated temperoparietal language areas. Several other brain regions were also involved in language processing apart from the classical language areas. [ABSTRACT FROM AUTHOR]

Language lateralization is one of the most prominent examples of functional hemispheric asymmetries. Previous studies indicate a significant contribution of factors not related to DNA sequence variation on the development of language lateralization, but the molecular processes underlying this relation are unclear. The Brandler-Paracchini model of hemispheric asymmetries assumes that genes involved in the establishment of ciliogenesis and bodily asymmetries also affect functional hemispheric asymmetries. Thus, genes implicated in this model represent a key target for epigenetic modulation of language lateralization. Here, we analyzed DNA methylation in the KIAA0319 (a gene involved in dyslexia and ciliogenesis) promoter region to investigate whether epigenetic markers of language lateralization can be identified in non-neuronal tissue. We found sex-specific effects of DNA methylation in single CpG sites on language lateralization in the forced-left (FL) and the forced-right (FR), but not on language lateralization in the non-forced (NF) condition of the dichotic listening task. These findings suggest that DNA methylation patterns in the KIAA0319 promoter region might be associated with cognitive control processes that are necessary to perform well in the forced-attention conditions. Furthermore, the assumption of an association between genes involved in ciliogenesis and the ontogenesis of functional hemispheric asymmetries is supported. [ABSTRACT FROM AUTHOR]

While object naming is traditionally considered asa left hemisphere function, neuroimaging studies have reported activations related to naming in the ventral temporal cortex (VTC) bilaterally. Our aim was to use intracerebral electrical stimulation to specifically compare left and right VTC in naming. In twenty-three epileptic patients tested for visual object naming during stimulation, the proportion of naming impairments was significantly higher in the left than in the right VTC (31.3% vs 13.6%). The highest proportions of positive naming sites were found in the left fusiform gyrus and occipito-temporal sulcus (47.5% and 31.8%). For 17 positive left naming sites, an additional semantic picture matching was carried out, always successfully performed. Our results showed the enhanced role of the left compared to the right VTC in naming and suggest that it may be involved in lexical retrieval rather than in semantic processing. [ABSTRACT FROM AUTHOR]

Handedness and language lateralization are partially determined by genetic influences. It has been estimated that at least 40 (and potentially more) possibly interacting genes may influence the ontogenesis of hemispheric asymmetries. Recently, it has been suggested that analyzing the genetics of hemispheric asymmetries on the level of gene ontology sets, rather than at the level of individual genes, might be more informative for understanding the underlying functional cascades. Here, we performed gene ontology, pathway and disease association analyses on genes that have previously been associated with handedness and language lateralization. Significant gene ontology sets for handedness were anatomical structure development, pattern specification (especially asymmetry formation) and biological regulation. Pathway analysis highlighted the importance of the TGF-beta signaling pathway for handedness ontogenesis. Significant gene ontology sets for language lateralization were responses to different stimuli, nervous system development, transport, signaling, and biological regulation. Despite the fact that some authors assume that handedness and language lateralization share a common ontogenetic basis, gene ontology sets barely overlap between phenotypes. Compared to genes involved in handedness, which mostly contribute to structural development, genes involved in language lateralization rather contribute to activity-dependent cognitive processes. Disease association analysis revealed associations of genes involved in handedness with diseases affecting the whole body, while genes involved in language lateralization were specifically engaged in mental and neurological diseases. These findings further support the idea that handedness and language lateralization are ontogenetically independent, complex phenotypes.

Despite significant scientific advances, the nature of the left-hemispheric systems involved in language (speech and gesture) and manual actions is still unclear. To date, investigations of human laterality focused mainly on non-communication functions. Although gestural laterality data have been published for infants and children, relatively little is known about laterality of human gestural communication. This study investigated human laterality in depth considering non-communication manipulation actions and various gesture types involving hands, feet, face and ears. We constructed an online laterality questionnaire including 60 items related to daily activities. We collected 317 594 item responses by 5904 randomly selected participants. The highest percentages of strong left-lateralized (6.76%) and strong right-lateralized participants (75.19%) were for manipulation actions. The highest percentages of mixed left-lateralized (12.30%) and ambidextrous (50.23%) participants were found for head-related gestures. The highest percentage of mixed right-lateralized participants (55.33%) was found for auditory gestures. Every behavioural category showed a significant population-level right-side bias. More precisely, participants were predominantly right-lateralized for non-communication manual actions, for visual iconic, visual symbolic, visual deictic (with and without speech), tactile and auditory manual gestures as well as for podial and head-related gestures. Our findings support previous studies reporting that humans have left-brain predominance for gestures and complex motor activities such as tool-use. Our study shows that the Rennes Laterality Questionnaire is a useful research instrument to assess and analyse human laterality for both manipulation and communication functions.

The corpus callosum has been proposed as a mechanism of interhemispheric inhibition that allows language dominance to develop [1]. Callosal agenesis or dysgenesis provides a test of this hypothesis, as patients lacking a normal corpus callosum should also lack normal language lateralization [2]. We report pre- and postoperative functional magnetic resonance imaging (fMRI) and neuropsychological testing in a patient with partial callosal agenesis who underwent a right temporal lobectomy for medically refractory seizures.

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. Methods Scalp EEG was recorded from 64 locations in 36 epilepsy patients and 37 controls during three visually presented language tasks: A short-term language memory task (differentiation memorized vs. unknown words), a phonological task (detection of rhymes in word pairs), and a semantic decision task (differentiation words vs. pseudowords). ERPs were analyzed in the 300 ms–800 ms epoch. Language fMRI was routinely obtained in patients. Results ERPs were significantly more negative over the left compared to the right hemisphere in all three tasks in patients and controls. Laterality indices showed highest concordance with fMRI for the Word/Pseudoword Task. Conclusions ERPs of language processing were lateralized to the left hemisphere in the majority of epilepsy patients and controls. In patients, single-subject laterality indices showed high concordance with fMRI results. Significance Results indicate that scalp-derived ERPs are a promising tool to investigate lateralization of language function in epilepsy patients. [ABSTRACT FROM AUTHOR]

Several studies analyzing the ontogenetic origin of cerebral lateralization provide evidences for a genetic foundation of handedness in humans that is modulated by environmental influences. Since other forms of behavioral lateralization are less investigated, it is unclear as to how far different functions display similar heritability. But deeper knowledge is necessary to understand if and how developmental coupling of different functions is based on a shared genetic background or on the impact of environmental influences. Here, we investigated the heritability of language lateralization assessed with the dichotic listening task, as well as the heritability of cognitive control processes modulating performance in this task. Overall, 103 families consisting of both parents and offspring were tested with the non-forced, as well as the forced-right and forced-left condition of the forced attention dichotic listening task, implemented in the iDichotic smartphone app, developed at the University of Bergen, Norway. The results indicate that the typical right ear advantage in the dichotic listening task shows weak and non-significant heritability (h2=0.003; p=0.98). In contrast, cognitive factors, like attention focus (forced right condition: h2=0.36; p<0.01; forced left condition: h2=0.28; p<0.05) and cognitive control (Gain forced right: h2=0.39; p<0.01; Gain forced left: h2=0.49; p<0.01) showed stronger and significant heritability. These findings indicate a variable dependence of different aspects of a cognitive function on heritability and implicate a major contribution of non-genetic influences to individual language lateralization. [ABSTRACT FROM AUTHOR]