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Research ArticleNew Research, Disorders of the Nervous System

Right Structural and Functional Reorganization in Four-Year-Old Children with Perinatal Arterial Ischemic Stroke Predict Language Production

Clément François, Pablo Ripollés, Laura Ferreri, Jordi Muchart, Joanna Sierpowska, Carme Fons, Jorgina Solé, Monica Rebollo, Robert J. Zatorre, Alfredo Garcia-Alix, Laura Bosch and Antoni Rodriguez-Fornells
eNeuro 5 August 2019, 6 (4) ENEURO.0447-18.2019; DOI: https://doi.org/10.1523/ENEURO.0447-18.2019
Clément François
1Cognition and Brain Plasticity Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona 08907, Spain
2Department of Cognition, Development and Educational Science, University of Barcelona, Barcelona 08035, Spain
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  • ORCID record for Clément François
Pablo Ripollés
3Poeppel Lab, Department of Psychology, New York University, NY 10003
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Laura Ferreri
1Cognition and Brain Plasticity Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona 08907, Spain
2Department of Cognition, Development and Educational Science, University of Barcelona, Barcelona 08035, Spain
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Jordi Muchart
4Institut de Recerca Sant Joan de Déu. Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona 08950, Spain
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Joanna Sierpowska
5Donders Institute for Brain, Cognition and Behaviour, Radboud University, 6525 HR, Nijmegen, The Netherlands
6Department of Medical Psychology, Radboud University Medical Center, Nijmegen, The Netherlands
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Carme Fons
4Institut de Recerca Sant Joan de Déu. Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona 08950, Spain
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Jorgina Solé
2Department of Cognition, Development and Educational Science, University of Barcelona, Barcelona 08035, Spain
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Monica Rebollo
4Institut de Recerca Sant Joan de Déu. Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona 08950, Spain
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Robert J. Zatorre
8Cognitive Neuroscience Unit, Montreal Neurological Institute, McGill University, Montreal H3A 2B4, Canada
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Alfredo Garcia-Alix
4Institut de Recerca Sant Joan de Déu. Hospital Sant Joan de Déu, Universitat de Barcelona, Barcelona 08950, Spain
7Service of Genetic and Molecular Medicine, Hospital Sant Joan de Déu, Barcelona 08950, Spain
9Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), U724, Madrid, Spain
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Laura Bosch
2Department of Cognition, Development and Educational Science, University of Barcelona, Barcelona 08035, Spain
10Institute of Neuroscience (UBNeuro), University of Barcelona, Barcelona, 08035, Spain
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Antoni Rodriguez-Fornells
1Cognition and Brain Plasticity Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona 08907, Spain
2Department of Cognition, Development and Educational Science, University of Barcelona, Barcelona 08035, Spain
11Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, 08010, Spain
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  • Figure 1.
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    Figure 1.

    A, Depiction of the structural lesions in native space using a T1-w axial image. The lesions can be seen as hypo-intense areas and are highlighted with a red circle. Neurologic convention is used. B, Individual DMNs for each patient, obtained using group spatial ICA on the resting state data (see Materials and Methods). Individual data are in z-scores (p < 0.05, uncorrected) and presented over each patient’s T1 registered to a common space (four-year-old MRI brain template obtained from the Neurodevelopmental MRI Database; see Materials and Methods). This was done as a demonstration of data quality, given that propofol can reduce connectivity in cortical areas of significance for the current study (Boveroux et al., 2010). On the right, the average DMN for all patients is depicted, using t values (p < 0.01, uncorrected) over a canonical four-year-old MRI brain template. C, Probability templates for the left arcuate (anterior, posterior, and long segment) were extracted from the Tractotron atlas (Thiebaut de Schotten et al., 2011; Rojkova et al., 2016), thresholded at a 80% (only voxels having a 80% probability of being part of the AF according to the atlas are shown) and registered to a common space (the four-year-old MRI brain template obtained from the Neurodevelopmental MRI Database). For each patient, here we depict the arcuate probabilistic atlas (in red), the lesion (in blue), and the overlap between them (in pink) over a sagittal slice of the left hemisphere. Neurologic convention is used. L, left hemisphere.

  • Figure 2.
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    Figure 2.

    Cognitive outcomes. A, Results of the PPVT-III test for each patient. The bars show the mean and SD. B, Means and SDs barplots of the composite scores from the NEPSY-II. The gray slots indicate normative scores range (8–12).

  • Figure 3.
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    Figure 3.

    Means and SDs boxplots in the different subtests of the NEPSY-II (CI, comprehension of instruction; BPNI, body-part naming and identification; WG, word generation; PP, phonological processing; SN, speeded naming; MD, memory for designs; NM, narrative memory; SR, sentence repetition; BC, block construction; DC, design copying; IHP, imitating hand positions; VMP, visuomotor precision) grouped in domains (green, language; orange, memory and learning; purple, visuospatial processing; blue, sensorimotor processing). The gray slot indicates normative scores range (8–12).

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    Figure 4.

    Expressive language measures. Means and SDs boxplots for children with PAIS and controls, for proximity and complexity scores. The graphs represent individual scores for the proximity score (A) for the pMLU scores (B) and from the referent group (N = 50), the group mean value (in black) and the score from each patient (in red). Maximum score for the pMLU score (complexity of the segmental structure of the words (consonants) is 8.31; maximum score for proximity score is 1. C, Utterance complexity in spontaneous speech with the MLU in words and the MLU of the five longest utterances (max-L) for each patient. The gray slots indicate the scores range from an age-matched control group of N = 50 Spanish-speaking children at age 4 (Vázquez and Alonso, 2007).

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    Figure 5.

    fMRI activation in the passive listening task for the language versus control contrast in patients. Two significant clusters with enhanced fMRI activity are found over the right inferior frontal and middle temporal gyri. Color-coded results are shown in yellow and at a p < 0.001, in red at p < 0.005, in green at p < 0.01, and in blue at p < 0.05 uncorrected threshold with five voxels of cluster extent, over the Neurodevelopmental MRI Database four-year-old template from Richards et al. (2016). Neurologic convention is used.

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    Figure 6.

    Deterministic tractography. DTI in vivo dissections of the four tracts of interest AF/ILF/UF/IFOF shown in native space on the T1-w images in each patient (A) and four controls (B). Neurologic convention is used. The two-ROI approach revealed that for all the children with a left PAIS (A), the three segments of the AF were well preserved in the right hemisphere. Meanwhile, we were not able to dissect the left AF in most of them (L4 and L6 presented the posterior segment only, whereas L1 presented the posterior and the long segment but not the anterior one). We did not observe any substantial damage for the ventral WM pathways (ILF, IFOF, and UF) in either hemisphere. By contrast, the three segments of the left AF were always present in control children (B). However, while the anterior and posterior segments of the right AF were always present in these children, we were not able to reconstruct the long segment of the AF in three controls.

  • Figure 7.
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    Figure 7.

    A, Correlation between DTI properties extracted from the manual reconstruction of the arcuate fasciculus bilaterally and productive aspects of language. The positive correlation between the lateralization index for the volume of the complete right AF and the maximum length of utterance (L-max) is shown. Lateralization index: values closer to –1 mean lateralization to the left, values around 0 represent a symmetrical distribution, values closer to 1 mean lateralization to the right. This result evidences that the more lateralized to the right is the integrity of the AF, the better the productive aspects of language. B, Correlation between rs-fMRI laterality indexes and productive aspects of language. The scatterplot shows the positive Spearman’s correlation between the lateralization index for the STG-IFG laterality index and the MLU. This result evidences that the more lateralized to the right the intrinsic connectivity between the regions connected by the AF, the better the productive aspects of language. A 3D render of the four-year-old template is displayed with the ROIs used in this analysis. Correlation index and p values are displayed.

Tables

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    Table 1.

    Children demographic data and lesions main features

    PatientcodeAge at scan(years)GenderGestational age at birth(weeks)Birth weight(g)Clinical debut(hours of age)Age of MRI diagnostic (d)VascularterritoryStroke volume at birth (ml)Motor impairment(hemiplegia)Epilepsya
    L14M413160Clonic seizures at 12 h4M2 L18890NoNo
    L23.5F412960Clonic seizures at 26 h10M4 L47428YesNo
    L34M403560Clonic seizures at 48 h20M1
    Post-bifurcation L
    17588NoNo
    L44F412600Clonic seizures at 18 h4M2 sup L27882NoNo
    L54M393340Clonic seizures at 24 h5M1
    Post-bifurcation L
    36512NoNo
    L63.5M403025Clonic seizures at 41 h5M1
    Post-bifurcation L
    23509YesNo
    • ↵a Epilepsy = at least two recurrent and unprovoked seizures.

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    Table 2.

    Phonological complexity and proximity scores for the children with PAIS (single values) and for the control group (means and SDs)

    Phonological complexityPhonological proximity
    L15.81*0.70*
    L27.560.90
    L38.030.97
    L47.590.91
    L57.750.93
    L67.910.95
    Controls7.44 (0.81)0.89 (0.09)
    • An asterisk indicates scores significantly different from the control group (p < 0.05) resulted from the modified t test.

    • View popup
    Table 3.

    Spontaneous utterance performance (MLU and L-max scores) for the children with PAIS and for the control group (means and SDs)

    MLUL-max
    L11.74*4*
    L24.29.4
    L34.19.8
    L44.19
    L54.29.2
    L63.67.8
    Controls3.66 (0.96)8.2 (2.16)
    • An asterisk indicates scores significantly different from the control group (p < 0.05) resulted from the modified t test.

    • View popup
    Table 4.

    Precise lesion location for each child with PAIS with the corresponding percentage over the total of the individual lesion size

    % of GM loss% of WM loss
    Patient codeLesion locationLeftRightLeftRight
    L1L precentral gyrus (39%)
    L IFG (19%)
    L postcentral gyrus (16%)
    L MFG (16%)
    0.37.2.5.
    L2L SMG (56%)
    L AG (33%)
    L STG (10%)
    4.4.7.7.
    L3L AG (40%)
    L MOG (25%)
    L SMG (12%)
    7.8.10.3.
    L4L postcentral gyrus (53%)
    L SMG (23%)
    L precentral gyrus (20%)
    4.3.0.8.
    L5L AG (28%)
    L STG (26%)
    L SMG (19%)
    L MTG (8%)
    12.1.7.4.
    L6L IFG (39%)
    L MFG (33%)
    L precentral gyrus (24%)
    0.6.1.7.
    • The percentage of WM and GM loss is also presented for each patient. MFG, middle frontal gyrus; SMG, supramarginal gyrus; AG, angular gyrus; MTG, middle temporal gyrus; MOG, middle occipital gyrus.

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Right Structural and Functional Reorganization in Four-Year-Old Children with Perinatal Arterial Ischemic Stroke Predict Language Production
Clément François, Pablo Ripollés, Laura Ferreri, Jordi Muchart, Joanna Sierpowska, Carme Fons, Jorgina Solé, Monica Rebollo, Robert J. Zatorre, Alfredo Garcia-Alix, Laura Bosch, Antoni Rodriguez-Fornells
eNeuro 5 August 2019, 6 (4) ENEURO.0447-18.2019; DOI: 10.1523/ENEURO.0447-18.2019

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Right Structural and Functional Reorganization in Four-Year-Old Children with Perinatal Arterial Ischemic Stroke Predict Language Production
Clément François, Pablo Ripollés, Laura Ferreri, Jordi Muchart, Joanna Sierpowska, Carme Fons, Jorgina Solé, Monica Rebollo, Robert J. Zatorre, Alfredo Garcia-Alix, Laura Bosch, Antoni Rodriguez-Fornells
eNeuro 5 August 2019, 6 (4) ENEURO.0447-18.2019; DOI: 10.1523/ENEURO.0447-18.2019
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Keywords

  • diffusion tensor imaging
  • fMRI
  • hyperconnectivity
  • interhemispheric plasticity
  • language production
  • perinatal arterial ischemic stroke

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