Regional and Hemispheric Determinants of Language Laterality: Implications for Preoperative fMRI

Language is typically a function of the left hemisphere but the right hemisphere is also essential in some healthy individuals and patients. This inter-subject variability necessitates the localization of language function, at the individual level, prior to neurosurgical intervention. Such assessments are typically made by comparing left and right hemisphere language function to determine “language lateralization” using clinical tests or fMRI. Here, we show that language function needs to be assessed at the region and hemisphere specific level, because laterality measures can be misleading. Using fMRI data from 82 healthy participants, we investigated the degree to which activation for a semantic word matching task was lateralized in 50 different brain regions and across the entire cortex. This revealed two novel findings. First, the degree to which language is lateralized across brain regions and between subjects was primarily driven by differences in right hemisphere activation rather than differences in left hemisphere activation. Second, we found that healthy subjects who have relatively high left lateralization in the angular gyrus also have relatively low left lateralization in the ventral precentral gyrus. These findings illustrate spatial heterogeneity in language lateralization that is lost when global laterality measures are considered. It is likely that the complex spatial variability we observed in healthy controls is more exaggerated in patients with brain damage. We therefore highlight the importance of investigating within hemisphere regional variations in fMRI activation, prior to neuro-surgical intervention, to determine how each hemisphere and each region contributes to language processing. Hum Brain Mapp, 2010. © 2010 Wiley-Liss, Inc

Surface Smoothing: A Way Back in Early Brain

Abstract. In this article we propose to investigate the analogy between early cortical folding process and cortical smoothing by mean curvature flow. First, we introduce a one-parameter model that is able to fit a developmental trajectory as represented in a Volume-Area plot and we propose an efficient optimization strategy for parameter estimation. Second, we validate the model on forty cortical surfaces of preterm newborns by comparing global geometrical indices and trajectories of central sulcus along developmental and simulation time.

Optimizing statistical parametric mapping analysis of 18F-FDG PET in children.

International audienceABSTRACT: BACKGROUND: Statistical parametric mapping (SPM) procedure is an objective tool to analyze 18F-fluoro-2-deoxy-d-glucose-positron-emission tomography (FDG-PET) images and a useful complement to visual analysis. However, SPM requires a comparison to control data set that cannot be obtained in healthy children for ethical reasons. Using adults as controls showed some limitations. The purpose of the present study was to generate and validate a group of pseudo-normal children as a control group for FDG-PET studies in pediatrics. METHODS: FDG-PET images of 47 children (mean +/- SD age 10.2 +/- 3.1 years) with refractory symptomatic (MRI-positive, n = 20) and cryptogenic (MRI-negative, n = 27) focal epilepsy planned for surgery were analyzed using visual and SPM analysis. Performances of SPM analysis were compared using two different control groups: (1) an adult control group consisting of healthy young adults (n = 25, 30.5 +/- 5.8 years, adult PET template) and (2) a pediatric pseudo-control group consisting of patients (n = 24, 10.6 +/- 3.1 years, children PET template) with refractory focal epilepsy; but negative MRI and PET are considered normal not only on visual analysis but also on SPM. RESULTS: Among the 47 children, visual analysis succeeded detecting at least one hypometabolic area in 87% of the cases (interobserver kappa = 0.81). Regarding SPM analysis, the best compromise between sensitivity and specificity was obtained with a threshold of p less than 0.001 as an extent of more than 40 voxels. There was a significant concordance to detect hypometabolic areas between both SPM analyses [kappa (K) = 0.59; p < 0.005] and between both SPM and visual analyses (K = 0.45; p < 0.005), in symptomatic (K = 0.74; p < 0.005) as in cryptogenic patients (K = 0.26; p < 0.01). The pediatric pseudo-control group dramatically improved specificity (97% vs. 89%; p < 0.0001) by increasing the positive predictive value (86% vs. 65%). Sensitivity remained acceptable although it was not better (79% vs. 87%, p = 0.039). The main impact was to reduce by 41% the number of hypometabolic cortical artifacts detected by SPM, especially in the younger epileptic patients, which is a key point in clinical practice. CONCLUSIONS: This age-matched pseudo-control group is a way to optimize SPM analysis of FDG-PET in children with epilepsy. It might also be considered for other brain pathologies in pediatrics in the future

Presurgical language mapping in children with epilepsy: Clinical usefulness of functional magnetic resonance imaging for the planning of cortical stimulation

Purpose: Presurgical language mapping in dominant hemisphere epilepsy to evaluate the risk of postoperative deficit is particularly difficult in children. Extraoperative invasive cortical stimulation can show some areas critical to language, but not all of them, due to scarce sampling, poor cooperation, cortical immaturity, or network reorganization, whereas functional magnetic resonance imaging (fMRI) displays entire networks involved in, but not necessarily critical to, language. In a homogeneous series of children with epilepsy, we compared the contributions of language fMRI and depth electrode stimulations to optimize language mapping. Methods: Eight children (7.5-15.5 years) with left frontal or temporal epilepsy underwent language fMRI and language stimulation with depth electrodes as part of their comprehensive presurgical workup. fMRI data collected during sentence generation were analyzed using statistical parametric mapping (SPM2) (false discovery rate [FDR] p \u3c 0.05). Bipolar stimulations were performed during language production tasks. By coregistering fMRI and postimplantation computed tomography (CT) images, we were able to directly compare the cortical areas identified by both investigations. Key Findings: fMRI during sentence generation robustly showed activation in the whole perisylvian regions with little reorganization (left hemisphere dominant in 7). Of the 184 electrode contacts tested for language, only 8 were positive (language disruption) in three of the seven patients with periictal language impairment and left language dominance. All of the positive contacts colocalized with an fMRI activated cluster, that is, fMRI did not miss any region critical to language (sensitivity = 100%). However, 54 of the 176 negative contacts were within activated clusters (low specificity). Significance: In children with epilepsy, the sensitivity of fMRI during sentence generation allows for the detection of all critical regions displayed by cortical stimulation within the large perisylvian language network, but with a low specificity. It is, therefore, useful to optimize the placement of intracranial electrodes when language mapping is necessary. Systematic planning of the electrode placement according to language fMRI maps should increase the yield of extraoperative cortical stimulation, which appears rather low in children when compared to adults. © 2011 International League Against Epilepsy

Motor Outcomes After Neonatal Arterial Ischemic Stroke Related to Early MRI Data in a Prospective Study

OBJECTIVE: We aimed to correlate early imaging data with motor outcomes in a large, homogeneous, cohort of infants with neonatal (diagnosed before 29 days of life) arterial ischemic stroke (AIS).METHODS: From a prospective cohort of 100 children with neonatal AIS, we analyzed the MRI studies performed within the 28 first days of life for 80 infants evaluated at 2 years of age. The relationships between infarction location and corticospinal tract (CST) involvement and motor outcomes were studied RESULTS: Seventy-three infarctions involved the middle cerebral artery (MCA) territory. Of those, 50 were superficial infarctions, 5 deep infarctions, and 18 mixed infarctions. The CST was involved in 24 cases. Nineteen patients with MCA infarctions (26% [95% confidence interval: 16%–34%]) developed hemiplegia. Mixed infarctions (P &lt; .0001) and CST involvement (P &lt; .0001) were highly predictive of hemiplegia. In contrast, 88% of children with isolated superficial MCA infarctions did not exhibit impairment. CONCLUSIONS: Accurate prediction of motor outcomes can be obtained from early MRI scans after neonatal AIS. The absence of involvement of the CST resulted in normal motor development in 94% of cases. CST involvement resulted in congenital hemiplegia in 66% of cases

Atlas-Free Surface Reconstruction of the Cortical Grey-White Interface in Infants

BACKGROUND: The segmentation of the cortical interface between grey and white matter in magnetic resonance images (MRI) is highly challenging during the first post-natal year. First, the heterogeneous brain maturation creates important intensity fluctuations across regions. Second, the cortical ribbon is highly folded creating complex shapes. Finally, the low tissue contrast and partial volume effects hamper cortex edge detection in parts of the brain. METHODS AND FINDINGS: We present an atlas-free method for segmenting the grey-white matter interface of infant brains in T2-weighted (T2w) images. We used a broad characterization of tissue using features based not only on local contrast but also on geometric properties. Furthermore, inaccuracies in localization were reduced by the convergence of two evolving surfaces located on each side of the inner cortical surface. Our method has been applied to eleven brains of one- to four-month-old infants. Both quantitative validations against manual segmentations and sulcal landmarks demonstrated good performance for infants younger than two months old. Inaccuracies in surface reconstruction increased with age in specific brain regions where the tissue contrast decreased with maturation, such as in the central region. CONCLUSIONS: We presented a new segmentation method which achieved good to very good performance at the grey-white matter interface depending on the infant age. This method should reduce manual intervention and could be applied to pathological brains since it does not require any brain atlas

Atypical Language Lateralization in Epilepsy Patients

Purpose:  To investigate whether atypical language dominance in epilepsy patients is related to localization and type of lesions. Methods:  Four hundred and forty-five epilepsy patients received bilateral Wada testing. Language was classified as left (L), right (R), bilateral-dependent (BD, speech arrest after left and right injections), or bilateral-independent (BI, no speech arrest after either injection). Groups were compared regarding handedness and magnetic resonance imaging (MRI) lesions. Lesions were classified as “early” (congenital), “late” neocortical (acquired after birth), and hippocampal sclerosis (HS). Results:  Of all patients, 78% were L, 6% R, 7% BD, and 9% BI. Right-handers with left lesions did not differ from those without lesions. Left-handers with normal MRI did not differ from right-handers. Left-handers with early left lesions were most likely R (46%). Left-handers with late neocortical left lesions were most likely BD (37%); those with left HS were most likely BD (33%) or L (33%). In both latter groups, R language was rare (13% and 11%, respectively). Discussion:  The data support the notion that R dominance may indicate development of functional language areas in the right hemisphere following an early insult. BD language may signal defective maintenance of right hemispheric language caused by a late left hemispheric insult at a time when left dominance has already started to develop. In contrast, BI language may represent a variant with functional language representation in both hemispheres

Typical asymmetry in the hemispheric activation during an fMRI verbal comprehension paradigm is related to better performance in verbal and non-verbal tasks in patients with epilepsy

Chronic exposure to seizures in patients with left hemisphere (LH) epileptic focus could favor higher activation in the contralateral hemisphere during language processing, but the cognitive effects of this remain unclear. This study assesses the relationship between asymmetry in hemispheric activation during language fMRI and performance in verbal and non-verbal tasks. Whereas prior studies primarily used fMRI paradigms that favor frontal lobe activation and less prominent activation of the medial or superior temporal lobes, we used a verbal comprehension paradigm previously demonstrated to activate reliably receptive language areas. Forty-seven patients with drug-resistant epilepsy candidates for surgery underwent a multidisciplinary assessment, including a comprehensive neuropsychological evaluation and an fMRI verbal comprehension paradigm. Patients were distributed in two groups depending on laterality indexes (LI): typical hemispheric asymmetry (unilateral left activation preponderance; n = 23) and atypical hemispheric asymmetry (bilateral or unilateral right preponderance; n = 24). Right-handedness and right hemisphere (RH) focus were significant predictors of typical asymmetry. Patients with typical activation pattern presented better performance intelligence quotient and verbal learning than patients with atypical hemispheric asymmetry (for all, p < 0.014). Patients with LH focus had more frequently atypical hemispheric asymmetry than patients with RH focus (p = 0.05). Specifically, they showed lower LI and this was related to worse performance in verbal and non-verbal tasks. In conclusion, an increased activation of homologous RH areas for verbal comprehension processing could imply a competition of cognitive resources in the performance of the same task, disrupting cognitive performance

Cortical auditory-evoked responses in preterm neonates: Revisited by spectral and temporal analyses

© The Author 2017. Published by Oxford University Press. Characteristic preterm EEG patterns of "Delta-brushes" (DBs) have been reported in the temporal cortex following auditory stimuli, but their spatio-temporal dynamics remains elusive. Using 32-electrode EEG recordings and co-registration of electrodes' position to 3D-MRI of age-matched neonates, we explored the cortical auditory-evoked responses (AERs) after 'click' stimuli in 30 healthy neonates aged 30-38 post-menstrual weeks (PMW). (1) We visually identified auditory-evoked DBs within AERs in all the babies between 30 and 33 PMW and a decreasing response rate afterwards. (2) The AERs showed an increase in EEG power from delta to gamma frequency bands over the middle and posterior temporal regions with higher values in quiet sleep and on the right. (3) Time-frequency and averaging analyses showed that the delta component of DBs, which negatively peaked around 550 and 750 ms over the middle and posterior temporal regions, respectively, was superimposed with fast (alpha-gamma) oscillations and corresponded to the late part of the cortical auditory-evoked potential (CAEP), a feature missed when using classical CAEP processing. As evoked DBs rate and AERs delta to alpha frequency power decreased until full term, auditory-evoked DBs are thus associated with the prenatal development of auditory processing and may suggest an early emerging hemispheric specialization

Relationships between Regional Radiation Doses and Cognitive Decline in Children Treated with Cranio-Spinal Irradiation for Posterior Fossa Tumors

Pediatric posterior fossa tumor (PFT) survivors who have been treated with cranial radiation therapy often suffer from cognitive impairments that might relate to IQ decline. Radiotherapy (RT) distinctly affects brain regions involved in different cognitive functions. However, the relative contribution of regional irradiation to the different cognitive impairments still remains unclear. We investigated the relationships between the changes in different cognitive scores and radiation dose distribution in 30 children treated for a PFT. Our exploratory analysis was based on a principal component analysis (PCA) and an ordinary least square regression approach. The use of a PCA was an innovative way to cluster correlated irradiated regions due to similar radiation therapy protocols across patients. Our results suggest an association between working memory decline and a high dose (equivalent uniform dose, EUD) delivered to the orbitofrontal regions, whereas the decline of processing speed seemed more related to EUD in the temporal lobes and posterior fossa. To identify regional effects of RT on cognitive functions may help to propose a rehabilitation program adapted to the risk of cognitive impairment