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Genome sequencing for rightward hemispheric language dominance.

ABSTRACT: Most people have left-hemisphere dominance for various aspects of language processing, but only roughly 1% of the adult population has atypically reversed, rightward hemispheric language dominance (RHLD). The genetic-developmental program that underlies leftward language laterality is unknown, as are the causes of atypical variation. We performed an exploratory whole-genome-sequencing study, with the hypothesis that strongly penetrant, rare genetic mutations might sometimes be involved in RHLD. This was by analogy with situs inversus of the visceral organs (left-right mirror reversal of the heart, lungs and so on), which is sometimes due to monogenic mutations. The genomes of 33 subjects with RHLD were sequenced and analyzed with reference to large population-genetic data sets, as well as 34 subjects (14 left-handed) with typical language laterality. The sample was powered to detect rare, highly penetrant, monogenic effects if they would be present in at least 10 of the 33 RHLD cases and no controls, but no individual genes had mutations in more than five RHLD cases while being un-mutated in controls. A hypothesis derived from invertebrate mechanisms of left-right axis formation led to the detection of an increased mutation load, in RHLD subjects, within genes involved with the actin cytoskeleton. The latter finding offers a first, tentative insight into molecular genetic influences on hemispheric language dominance.

SUBMITTER: Carrion-Castillo A

PROVIDER: S-EPMC6850193 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Genome sequencing for rightward hemispheric language dominance.

Carrion-Castillo Amaia A Van der Haegen Lise L Tzourio-Mazoyer Nathalie N Kavaklioglu Tulya T Badillo Solveig S Chavent Marie M Saracco Jérôme J Brysbaert Marc M Fisher Simon E SE Mazoyer Bernard B Francks Clyde C

Genes, brain, and behavior 20190423 5

Most people have left-hemisphere dominance for various aspects of language processing, but only roughly 1% of the adult population has atypically reversed, rightward hemispheric language dominance (RHLD). The genetic-developmental program that underlies leftward language laterality is unknown, as are the causes of atypical variation. We performed an exploratory whole-genome-sequencing study, with the hypothesis that strongly penetrant, rare genetic mutations might sometimes be involved in RHLD. ...[more]

PMID: 30950222

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Project description:ObjectiveThe intracarotid amobarbital procedure (IAP) is the current "gold standard" in the preoperative assessment of language lateralization in epilepsy surgery candidates. It is, however, invasive and has several limitations. Here we tested a simple noninvasive language lateralization test performed with magnetoencephalography (MEG).MethodsWe recorded auditory MEG responses to pairs of vowels and pure tones in 16 epilepsy surgery candidates who had undergone IAP. For each individual, we selected the pair of planar gradiometer sensors with the strongest N100m response to vowels in each hemisphere and-from the vector sum of signals of this gradiometer pair-calculated the vowel/tone amplitude ratio in the left (L) and right (R) hemisphere and, subsequently, the laterality index: LI = (L-R)/(L+R). In addition to the analysis using a single sensor pair, an alternative analysis was performed using averaged responses over 18 temporal sensor pairs in both hemispheres.ResultsThe laterality index did not correlate significantly with the lateralization data obtained from the IAP. However, an MEG pattern of stronger responses to vowels than tones in the left hemisphere and stronger responses to tones than vowels in the right hemisphere was associated with left-hemispheric language dominance in the IAP in all the six patients who showed this pattern. This results in a specificity of 100% and a sensitivity of 67% of this MEG pattern in predicting left-hemispheric language dominance (p = 0.01, Fisher's exact test). In the analysis using averaged responses over temporal channels, one additional patient who was left-dominant in IAP showed this particular MEG pattern, increasing the sensitivity to 78% (p = 0.003).SignificanceThis simple MEG paradigm shows promise in feasibly and noninvasively confirming left-hemispheric language dominance in epilepsy surgery candidates. It may aid in reducing the need for the IAP, if the results are confirmed in larger patient samples.

Project description:BackgroundPre-surgical mapping of language using functional MRI aimed principally to determine the dominant hemisphere. This mapping is currently performed using covert linguistic task in way to avoid motion artefacts potentially biasing the results. However, overt task is closer to natural speaking, allows a control on the performance of the task, and may be easier to perform for stressed patients and children. However, overt task, by activating phonological areas on both hemispheres and areas involved in pitch prosody control in the non-dominant hemisphere, is expected to modify the determination of the dominant hemisphere by the calculation of the lateralization index (LI).ObjectiveHere, we analyzed the modifications in the LI and the interactions between cognitive networks during covert and overt speech task.MethodsThirty-three volunteers participated in this study, all but four were right-handed. They performed three functional sessions consisting of (1) covert and (2) overt generation of a short sentence semantically linked with an audibly presented word, from which we estimated the "Covert" and "Overt" contrasts, and a (3) resting-state session. The resting-state session was submitted to spatial independent component analysis to identify language network at rest (LANG), cingulo-opercular network (CO), and ventral attention network (VAN). The LI was calculated using the bootstrapping method.ResultsThe LI of the LANG was the most left-lateralized (0.66 ± 0.38). The LI shifted from a moderate leftward lateralization for the Covert contrast (0.32 ± 0.38) to a right lateralization for the Overt contrast (- 0.13 ± 0.30). The LI significantly differed from each other. This rightward shift was due to the recruitment of right hemispheric temporal areas together with the nodes of the CO.ConclusionAnalyzing the overt speech by fMRI allowed improvement in the physiological knowledge regarding the coordinated activity of the intrinsic connectivity networks. However, the rightward shift of the LI in this condition did not provide the basic information on the hemispheric language dominance. Overt linguistic task cannot be recommended for clinical purpose when determining hemispheric dominance for language.

Project description:PurposeLimited restoration of function is known to occur spontaneously after an ischemic injury to the primary motor cortex. Evidence suggests that Pre-Motor Areas (PMAs) may "take over" control of the disrupted functions. However, little is known about functional reorganizations in PMAs. Forelimb movements in mice can be driven by two cortical regions, Caudal and Rostral Forelimb Areas (CFA and RFA), generally accepted as primary motor and pre-motor cortex, respectively. Here, we examined longitudinal changes in functional coupling between the two RFAs following unilateral photothrombotic stroke in CFA (mm from Bregma: +0.5 anterior, +1.25 lateral).MethodsLocal field potentials (LFPs) were recorded from the RFAs of both hemispheres in freely moving injured and naïve mice. Neural signals were acquired at 9, 16 and 23 days after surgery (sub-acute period in stroke animals) through one bipolar electrode per hemisphere placed in the center of RFA, with a ground screw over the occipital bone. LFPs were pre-processed through an efficient method of artifact removal and analysed through: spectral,cross-correlation, mutual information and Granger causality analysis.ResultsSpectral analysis demonstrated an early decrease (day 9) in the alpha band power in both the RFAs. In the late sub-acute period (days 16 and 23), inter-hemispheric functional coupling was reduced in ischemic animals, as shown by a decrease in the cross-correlation and mutual information measures. Within the gamma and delta bands, correlation measures were already reduced at day 9. Granger analysis, used as a measure of the symmetry of the inter-hemispheric causal connectivity, showed a less balanced activity in the two RFAs after stroke, with more frequent oscillations of hemispheric dominance.ConclusionsThese results indicate robust electrophysiological changes in PMAs after stroke. Specifically, we found alterations in transcallosal connectivity, with reduced inter-hemispheric functional coupling and a fluctuating dominance pattern. These reorganizations may underlie vicariation of lost functions following stroke.

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Genome sequencing for rightward hemispheric language dominance.

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Genome sequencing for rightward hemispheric language dominance.

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