This longitudinal study, titled "Longitudinal assessment of multidomain reading-FREE neurocognitive markers for early detection of Developmental Dyslexia (FREE-DD)", investigates early neurocognitive predictors of developmental dyslexia (DD) and related reading disorders in children born preterm (PTB), as compared to children born at term (ATB). Children born preterm are at elevated risk for neurodevelopmental vulnerabilities, including difficulties with language, attention, and reading acquisition, yet early identification of these risks remains limited.
The main objective of the study is to identify early connectomic and neurocognitive markers-obtained during second grade-that can predict the development of reading difficulties in PTB children by third grade. Particular emphasis is placed on connectomic features derived from functional and structural brain imaging, as well as on a specially designed behavioral tool: the Reading-Free Screening Tool (RFST), which assesses reading-related cognitive abilities without requiring the child to read.
The study adopts a prospective, longitudinal, monocentric cohort design, with two assessment waves:
* Grade 2 (Baseline/Timepoint 1): All enrolled children will undergo a comprehensive neuropsychological battery, RFST administration, and MRI acquisition (including structural and resting-state functional MRI).
* Grade 3 (Follow-up/Timepoint 2): Children will be reassessed using the RFST and neuropsychological tests to track changes in cognitive and reading-related abilities.
The study population includes 30 preterm-born (PTB) children and 15 term-born (ATB) children, all aged between 6 and 9 years, native Italian speakers, and right-handed. Children with structural brain lesions, congenital anomalies, or known neurological/psychiatric conditions will be excluded.
Primary Objective The primary goal is to determine whether functional brain network characteristics (measured via resting-state fMRI), along with morpho-structural, microstructural, and cognitive metrics collected at grade 2, can predict changes in RFST performance and reading skills between grade 2 and grade 3.
Secondary Objectives
Secondary aims include:
* Assessing correlations between functional connectivity and RFST indices.
* Evaluating whether measures of brain network segregation and integration can classify PTB vs. ATB readers and forecast individual developmental trajectories.
* Identifying multimodal predictors of atypical reading profiles across both grades.
Exploratory Objectives The study also seeks to explore the role of combined behavioral and neuroimaging data in outlining early neurocognitive trajectories specific to prematurity, which may indicate susceptibility to developmental dyslexia and related disorders. These exploratory outcomes will help refine developmental models and screening strategies.
Methodology
Participants will complete:
* Parental questionnaires (screening and developmental history),
* Manual preference testing,
* Two waves of neuropsychological assessments targeting language, attention, memory, phonological processing, and non-verbal intelligence,
* RFST administration,
* MRI scanning (T1-weighted structural imaging and resting-state fMRI). Data Analysis
Analysis will proceed in three main steps:
1. Functional Connectivity Mapping: Correlating ROI-to-ROI functional brain connectivity with RFST indices across all participants.
2. Group Classification: Extracting graph-based network metrics (e.g., segregation, integration) to classify PTB vs. ATB participants.
3. Predictive Modeling (PTB group): Employing the most relevant imaging and behavioral features to predict changes in RFST performance between grades 2 and 3, modeling individual developmental outcomes.
Timeline and Duration
* Enrollment Period: 2 months
* Total Participant Commitment: Approx. 4 hours (2 hours per visit across two school years)
* Study Duration: 10-12 months (including follow-up) This study is sponsored by the Università Vita-Salute San Raffaele and funded by PRIN (Progetti di Ricerca di Rilevante Interesse Nazionale - Bando 2022, Prot. 2022TA92HS). It will be conducted at the clinical center of the Ospedale San Raffaele (OSR), under the direction of the U.O. of Neuroradiology.
The findings from this study aim to inform the development of screening tools and targeted early interventions for children born preterm, potentially reducing the long-term impact of developmental dyslexia and enhancing academic and cognitive outcomes.
