Poster No:
2456
Submission Type:
Abstract Submission
Authors:
Denis Peruzzo1, Alice Giubergia1,2, Filippo Arrigoni3, Alessio Toraldo4,5, Chiara Andreola6, Martina Villa7,8, Valentina Lampis1,4, Giorda Roberto1, Marco Villa1, Sara Mascheretti4,1
Institutions:
1Scientific Institute IRCCS Eugenio Medea, Bosisio Parini (LC), Italy, 2University of Padova, Padova (PD), Italy, 3V. Buzzi Children’s Hospital, Milano (MI), Italy, 4University of Pavia, Pavia (PV), Italy, 5Milan Centre for Neuroscience (NeuroMI), Milano (MI), Italy, 6Université Paris Cité, Paris, France, 7University of Connecticut, Storrs (CT), USA, 8Yale Child Study Center Language Sciences Consortium, New Haven (CT), USA
First Author:
Denis Peruzzo
Scientific Institute IRCCS Eugenio Medea
Bosisio Parini (LC), Italy
Co-Author(s):
Alice Giubergia
Scientific Institute IRCCS Eugenio Medea|University of Padova
Bosisio Parini (LC), Italy|Padova (PD), Italy
Alessio Toraldo
University of Pavia|Milan Centre for Neuroscience (NeuroMI)
Pavia (PV), Italy|Milano (MI), Italy
Martina Villa
University of Connecticut|Yale Child Study Center Language Sciences Consortium
Storrs (CT), USA|New Haven (CT), USA
Valentina Lampis
Scientific Institute IRCCS Eugenio Medea|University of Pavia
Bosisio Parini (LC), Italy|Pavia (PV), Italy
Giorda Roberto
Scientific Institute IRCCS Eugenio Medea
Bosisio Parini (LC), Italy
Marco Villa
Scientific Institute IRCCS Eugenio Medea
Bosisio Parini (LC), Italy
Sara Mascheretti
University of Pavia|Scientific Institute IRCCS Eugenio Medea
Pavia (PV), Italy|Bosisio Parini (LC), Italy
Introduction:
Developmental Dyslexia (DD) is a complex, heritable, language-based disorder resulting in impaired reading skills with no evident cognitive or sensory causes. Different candidate genes for DD have been identified, usually involved in neuronal migration, neurite outgrowth, cortical morphogenesis and ciliary structure and function [2]. In this study, we aim to exploit fMRI to investigate the relationship between the phenotype (i.e. the reading skills) and the genotype (i.e. the presence or absence of the deletion of the READ1 regulatory term in the DCDC2 gene). READ1 deletion (READ1-d) has already been associated with structural and functional alterations, both in children with DD and in TRs [1,3,5,6]. This study implements a genetic-imaging approach that uses the MRI derived measures as an intermediate phenotype to connect specific genetic variants (READS1-d) to cognitive phenotypes (Reading skills).
Methods:
Participants: The recruited dataset comprised 79 subjects: 18 children with DD and READ1-d (DD+), 21 children with DD and without READ1-d (DD-), 19 typical readers with READ1-d (TR+), and 21 TR without READ1-d (TR-). TRs and children with DD showed significant differences in terms of age, gender distribution, QI, and DSM-IV-Inattention (DSM-IV-I) traits.
fMRI Task and Acquisition: fMRI images (voxel size=2x2x2.7mm³; TR=2s) were acquired during the administration of two visual tasks involving the Magno (M) dorsal, the Parvo (P) ventral pathways, and the attentive network were implemented, a full-field Sinusoidal Gratings (SG) and a sensitivity to Coherent Motion (CM) [4].
fMRI Data Processing: The fMRI data were processed following the FreeSurfer Functional Analysis Stream (FSFAST) to the computation of two contrast maps for the SG task (M-vs-B: M stimulus vs. Baseline; P-vs-B: P stimulus vs. Baseline) and three for the CM task depending on the coherence dot level in the stimulus (CML6-vs-B; CML15-vs-B; CML40-vs-B). Average contrast values were computed in each ROI following the HCP-MMP1 parcellation of the cortex.
Statistical Analysis: contrast values were investigated using a univariate General Linear Model including as predictor the product between genetic variant and reading skills (i.e. READ1-d*Mean Reading) as a term to investigate the direct genotype-phenotype interaction we are interested in.
The models included as covariates also other demographic (age, gender), cognitive (IQ, DSM-IV-I score, mean reading score) and genetic (READ1-d) predictors.
Results:
At the Bonferroni-corrected level of significance (p<0.00014), we found a significant interaction effect between READ1-d and "Mean Reading'' in the left frontal opercular area 4 during the coherent motion sensitivity task at 15% dot coherence level. More specifically, among children with DD, READ1-d carriers had lower neural activation compared to their counterparts without READ1-d. Such a difference changes as a function of reading proficiency, with the gap closing and turning non-significant among TRs.
Conclusions:
We showed here how MRI derived measures can be used as an intermediate phenotype to investigate the relationship between genetic variants and cognitive phenotypes. In particular, we identified a region lying in the Ventral Attention Network (VAN) showing an altered cortical activation during the processing of a visual motion task in the combination of genetic variant (READ1-d) and poor reading skills. This result supports the hypothesis of a sluggish attentional shifting during the processing of stimuli targeting the magno pathways in children with weak reading performance and READ1-d.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism)
Genetics:
Genetics Other
Language:
Language Other 2
Lifespan Development:
Early life, Adolescence, Aging
Perception, Attention and Motor Behavior:
Attention: Visual 1
Keywords:
FUNCTIONAL MRI
Language
PEDIATRIC
1|2Indicates the priority used for review
Provide references using author date format
[1] Cope, N. (2012) 'Variants in the DYX2 locus are associated with altered brain activation in reading-related brain regions in subjects with reading disability', NeuroImage, 63(1):148-156. doi:10.1016/j.neuroimage.2012.06.037
[2] Lampis, V. (2021) 'Animal models of developmental dyslexia: Where we are and what we are missing', Neuroscience & Biobehavioral Reviews. 131:1180-1197. doi:10.1016/j.neubiorev.2021.10.022
[3] Marino, C. (2014) 'The DCDC2/intron 2 deletion and white matter disorganization: focus on developmental dyslexia', Cortex, 57:227-243. doi:10.1016/j.cortex.2014.04.016
[4] Mascheretti, S. (2021) 'Selecting the Most Relevant Brain Regions to Classify Children with Developmental Dyslexia and Typical Readers by Using Complex Magnocellular Stimuli and Multiple Kernel Learning', Brain Sciences, 11(6). doi:10.3390/brainsci11060722
[5] Meda, S. A. (2008) 'Polymorphism of DCDC2 Reveals Differences in Cortical Morphology of Healthy Individuals—A Preliminary Voxel Based Morphometry Study', Brain Imaging and Behavior, 2(1):21-26. doi:10.1007/s11682-007-9012-1
[6] Perani, D. (2021) 'White matter deficits correlate with visual motion perception impairments in dyslexic carriers of the DCDC2 genetic risk variant', Experimental Brain Research, 239(9):2725-2740. doi:10.1007/s00221-021-06137-1