The neurobiological substrates that cause people with dyslexia to experience difficulty in acquiring accurate and fluent reading skills are still largely unknown. Although structural and functional brain anomalies associated with dyslexia have been reported in adults and school-age children, these anomalies may represent differences in reading experience rather than the etiology of dyslexia. Conducting MRI studies of pre-readers at risk for dyslexia is one approach that enables us to identify brain alterations that exist before differences in reading experience emerge. The current review summarizes MRI studies that examine brain differences associated with risk for dyslexia in children before reading instruction and meta-analyzes these studies. In order to link these findings with current etiological theories of dyslexia, we focus on studies that take a modular perspective rather than a network approach. Although some of the observed differences in pre-readers at risk for dyslexia may still be shaped by language experiences during the first years of life, such studies underscore the existence of reading-related brain anomalies prior to reading onset and could eventually lead to earlier and more precise diagnosis and treatment of dyslexia.

The double-deficit hypothesis of dyslexia posits that both rapid naming and phonological impairments can cause reading difficulties, and that individuals who have both of these deficits show greater reading impairments compared to those with a single deficit. Despite extensive behavioral research, the brain basis of poor reading with a double-deficit has never been investigated. The goal of the study was to evaluate the double-deficit hypothesis using functional MRI. Activation patterns during a printed word rhyme judgment task in 90 children with a wide range of reading abilities showed dissociation between brain regions that were sensitive to phonological awareness (left inferior frontal and inferior parietal regions) and rapid naming (right cerebellar lobule VI). More specifically, the double-deficit group showed less activation in the fronto-parietal reading network compared to children with only a deficit in phonological awareness, who in turn showed less activation than the typically-reading group. On the other hand, the double-deficit group showed less cerebellar activation compared to children with only a rapid naming deficit, who in turn showed less activation than the typically-reading children. Functional connectivity analyses revealed that bilateral prefrontal regions were key for linking brain regions associated with phonological awareness and rapid naming, with the double-deficit group being the most aberrant in their connectivity. Our study provides the first functional neuroanatomical evidence for the double-deficit hypothesis of developmental dyslexia.

Imaging genetics provides an opportunity to discern associations between genetic variants and brain imaging phenotypes. Historically, the field has focused on adults and adolescents; very few imaging genetics studies have focused on brain development in infancy and early childhood (from birth to age 6 years). This is an important knowledge gap because developmental changes in the brain during the prenatal and early postnatal period are regulated by dynamic gene expression patterns that likely play an important role in establishing an individual's risk for later psychiatric illness and neurodevelopmental disabilities. In this review, we summarize findings from imaging genetics studies spanning from early infancy to early childhood, with a focus on studies examining genetic risk for neuropsychiatric disorders. We also introduce the Organization for Imaging Genomics in Infancy (ORIGINs), a working group of the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium, which was established to facilitate large-scale imaging genetics studies in infancy and early childhood.