Dysfunction of the visual sensory thalamus in developmental dyslexia

Abstract

Developmental dyslexia (DD) is a reading disorder with a prevalence of 5-10%. Neuroscientific research has typically focused on explaining DD symptoms based on pathophysiological changes in the cerebral cortex. However, DD might also be associated with alterations in sensory thalami - central subcortical stations of sensory pathways. A post-mortem study on the visual sensory thalamus (lateral geniculate nucleus, LGN) showed histopathological changes in the magnocellular (M-LGN), but not in the parvocellular (P-LGN), subdivisions. M-LGN and P-LGN have different functional properties and belong to two different visual systems. Whether M-LGN alterations also exist in DD in-vivo is unclear. Also, the potential relevance of M-LGN alterations to DD symptoms is unknown. This lack of knowledge is partly due to considerable technical challenges in investigating LGN subdivisions non-invasively in humans. Here, we employed recent advances in high-field 7 Tesla functional magnetic resonance imaging (fMRI) to map the M- and P-LGN in-vivo in DD adults (n=26) and matched controls (n=28). We show that (i) M-LGN responses differ between DD and control participants, (ii) these differences are more pronounced in male than in female DD participants, and (iii) M-LGN alterations predict a core symptom of DD in male DD participants only, i.e., rapid naming ability. Our results provide a first functional interpretation of M-LGN changes in DD and support DD theories that propose a direct relevance of sensory thalamus alterations for DD symptoms. In addition, the sex-specific behavioral relevance of M-LGN alterations within DD calls for taking sex differences into account when planning brain-based therapeutic interventions. Significance StatementDevelopmental dyslexia (DD) is one of the most common learning disorders affecting millions of children and adults world-wide. Several decades ago, pioneering research in five DD post-mortem brains suggested that DD is characterized not only by alterations of the cerebral cortex, but also by changes in a subsection of the visual sensory thalamus - the so-called M-LGN. The relevance of these findings for DD remained highly controversial. Using recent developments in high-resolution functional neuroimaging, we now discovered that M-LGN alterations are present also in DD in-vivo and predict a core symptom of DD in males. Our results provide a first functional interpretation of M-LGN alterations in DD and provide a basis for better understanding sex-specific differences in DD.