Materials and Methods P ARTICIPANTS

Fourteen dyslexic participants (6 females, mean age: 23.29 years, S.D.: 6.08) and 14 normal readers, matched in age and gender (6 females, mean age: 26.07 years, S.D.: 6.19) took part in this study. All were right-handed (scores ≥70 on the Edinburgh Handedness Inventory [51]), and all had audiometric pure-tone thresholds ≤25 dB on a frequency range from 250 to 8000 Hz. Statistical analysis (t-test, all P>0.05) confirmed that both groups did not differ in age, nonverbal-IQ or handedness (Table 2.5). All dyslexics reported a childhood history of reading/spelling disorders and all but one participant of the Normal Readers group were in addition screened for reading, spelling, phonological and verbal short-term memory abilities.

Participants reported no history of psychiatric or neurological disorders. All participants provided written informed consent and were paid for their participation; the protocol used

Chapitre 2D. Asymétries et perception de la parole dans le bruit chez le sujet dyslexique

in this experiment obtained approval from a local ethics committee (CPP Sud-Est IV, Lyon; ID RCB: 2008-A00708-47).

P

Nonverbal-IQ was assessed using the Raven Standard Progressive Matrices [52]. All participants obtained scores above the 50^th percentile. Reading-age was assessed using the French ‘Alouette Reading Test’ [53], and the neuropsychological battery ODEDYS [54] was administered to all participants. This battery evaluates reading and spelling, metaphonology (acronyms and phoneme deletion), verbal short term memory, visual attention and rapid automatized naming. Participants also performed a speech-in-noise intelligibility task, involving the perception of words presented in background babble. Materials and procedure have been described previously [14]. Three listening configurations were used: Dichotic, Monaural and Spatialised. In the Dichotic configuration, target words were presented in one ear whereas babble was presented in the other ear at the same intensity. In the Monaural configuration, target speech and babble background were presented in one ear only, on the right side. Finally, in the Spatialised configuration, target speech and babble background were presented in both ears, but with an interaural level difference for the background of 10dB, thus mimicking a listening situation in which target and background are slightly separated in space. Intelligibility scores were obtained by calculating the proportion of words correctly repeated. A two-way ANOVA was performed, with Group (Normal Readers and Dyslexics) as between-subject factor and Configuration (Dichotic, Monaural, and Spatialised) as within-subject factor. Statistical tests were performed using a P<0.05 threshold, and a post-hoc Bonferroni test was used on statistically significant differences.

I

MRI acquisition was performed at the hospital La Timone (Marseilles, France), using a 3.0T Brucker Medspec 30/80 AVANCE scanner. A 3D structural image was acquired for each subject using a T1 weighted MPRAGE sequence (TR: 9.4ms, TE: 4.42ms, pulse angle: 30°, field of view: 256 x 256 x 180 mm, matrix: 256 x 256 x 180) with a final resolution of 1 mm³.

A

Analyses were carried out using the VBM8 toolbox (Gaser, http://dbm.neuro.uni-jena.de/vbm), which uses the unified segmentation approach implemented in SPM8

(Wellcome Department of Imaging Neuroscience,

http://www.fil.ion.ucl.ac.uk/spm/software/spm8/). Images were bias-corrected, segmented into GM, WM and cerebro-spinal fluid (CSF), and normalized on the SPM T1 template into the same model. In addition this toolbox extends the unified segmentation with a maximum a posteriori (MAP) technique [55] and Partial Volume Estimation (PVE) to account for partial

Chapitre 2D. Asymétries et perception de la parole dans le bruit chez le sujet dyslexique

Page 190

volume effects [56]. For asymmetry analyses, we used voxel-wise analysis of asymmetry, an extension of the VBM procedure described previously [40,57-59]. Segmentation was performed using a symmetric a priori template, provided with the VBM8 Toolbox. Jacobian modulation was applied in order to preserve local gray and white matter values and voxel values were multiplied by the non-linear components of the registration in order to account for individual brain sizes. Resulting GM and WM modulated images were then flipped, and asymmetry images created from original and flipped images, using the following formula:

(original – flipped)/0.5*(original + flipped). Finally, the resulting asymmetry images were smoothed using a Gaussian kernel of 8 mm (FWHM).

Statistical analyses were performed using the General Linear Model (GLM) [60] implemented in SPM8, according to a two-steps procedure: first, whole-brain asymmetries in GM and WM asymmetry images were investigated in the whole sample of participants (N=28), using a one sample t-test including age and gender as covariables of non-interest. Statistical threshold was set at P<0.0005, with a P<0.005 cluster extent threshold. On obtained maps, statistical differences displayed on the right side represent a rightward morphological asymmetry. The SPM extension Anatomical Automatic Labelling [61] and when necessary Talairach Daemon [62,63] were used for localizing the effects. Secondly, group differences were investigated using a two-sample t-test restricted to superior temporal regions using small volume correction (SVC) with a statistical threshold set at P<0.05 FWE-corrected. Anatomical regions for the SVC correction were defined using WFU-PickAtlas [64,65]; in this toolbox Talairach Daemon database was used to generate regions selected to cover superior temporal regions: left and right BA 41, left and right BA 42; in addition, non-primary auditory regions of the superior temporal gyrus (corresponding to BA 22) were divided into three regions using Marsbar Toolbox (http://marsbar.sourceforge.net/) [66], namely left and right anterior, medial and posterior STG. Age, gender and nonverbal-IQ were added as covariables of non-interest. Correlation between asymmetry and performances on the speech-in-noise intelligibility test was investigated in each group separately. As dyslexics showed a deficit compared to normal readers only in the Monaural configuration, we did not add the two other configurations in the model. For this analysis, one subject from the Normal Readers group was discarded due to missing data.

V

B

M

In order to complete our observations on GM and WM volumes in the superior temporal regions, VBM analyses were subsequently carried out using the VBM8 toolbox. Images were bias corrected, segmented into GM, WM and CSF; normalization in the MNI space was performed using a high-dimensional DARTEL algorithm and a DARTEL template of 550 healthy participants provided in the toolbox. In order to preserve local gray and white matter values, a Jacobian modulation was applied. Voxel values were multiplied by the non-linear components of the registration which allows comparing absolute amounts of tissue

Chapitre 2D. Asymétries et perception de la parole dans le bruit chez le sujet dyslexique

corrected for individual brain size. To control the quality of this procedure, covariance between the resulting images was calculated to check homogeneity of variance and identify potential outliers. Finally, modulated normalized images were smoothed using a Gaussian kernel of 10 mm. Gray and white matter volume differences between normal readers and dyslexics were investigated using a t-statistic on a voxel-by-voxel basis. In order to remove age and gender biases from the data, these two variables were included as regressors of non-interest, and to avoid a possible edge effect between different tissue types, voxels with gray or white matter values of less than 0.1 were excluded (absolute threshold masking).

Following a priori hypotheses, SVC was applied in the superior temporal regions (left and right BA 41, BA 42 and anterior, medial and posterior STG) with a threshold of P<0.05 FWE corrected.

Results