Deficits in Function and Functional Connectivity of Left Occipitotemporal Cortex in Children with Dyslexia

Abstract

Reading is of enormous importance in our modern information-based society and an essential activity in everyday life. While most children successfully learn to read within a few years, reading acquisition is severely impaired in about 5-10% of children, resulting in a specific reading disorder called “developmental dyslexia”. One of the core deficits of individuals with dyslexia is impaired automatic word recognition, which leads to slow, dysfluent reading. Neuroimaging studies in adult readers have linked this orthographic processing deficit to deficits in a specific section of the left occipitotemporal cortex (the visual word form area; VWFA) involved in visual word processing. However, the exact function of the VWFA and the larger left occipitotemporal VWF-system in healthy children, as well as its dysfunctioning in dyslexic children is still unclear. In addition, since the VWF-system and its core region (the VWFA) are part of the typical language network that encompasses several other regions crucially involved in reading, there is considerable interest in examining the connectivity between those brain areas. This Ph.D. thesis aimed to investigate both the function and functional connectivity comparing control children and children with dyslexia. In Study A we examined (i) two levels of functional specialization of visual word processing − (a) coarse specialization for print and (b) sensitivity to orthographic familiarity of letter strings − in the left occipitotemporal VWFsystem in control children, and (ii) whether these types of specialization were impaired in children with dyslexia. In Study B we investigated (i) the functional connectivity of the VWF-system and other major components of the language network in control children, and (ii) whether these connections were different in dyslexic children. We tested 18 dyslexic and 24 age-matched control children (age 9.7- 12.5 years) while they indicated if visual stimuli (real words, pseudohomophones, pseudowords and false-fonts) sounded like a real word. Five adjacent regions of interest (ROIs) in the bilateral occipitotemporal cortex were selected to cover the full anterior-posterior extent of the VWFsystem. In Study A, we used functional MRI to assess the brain activity in response to four types of visual letter strings varying in orthographic familiarity. In Study B, we used functional connectivity MRI to examine interregional cooperation within the language network, focussing on the VWFA. The results from Study A revealed that control children show a dissociation of two functional levels of specialization within the VWF-system: (1) coarse specialization for print, i.e. different processing of letter strings than of visual control stimuli and (2) sensitivity to orthographic familiarity of letter strings. Furthermore, we showed that both of these functional levels of VWF-system specialization could not be detected in children with dyslexia in the entire VWF-system. To answer the question whether this functional impairment of the VWF-system is associated with impaired cooperation of this system with other language areas, we looked at the functional connectivity of these regions. The results from Study B revealed that, in control children, the functional connections with typical language areas (left inferior parietal lobule and left inferior frontal gyrus) were specific for the VWFA and did not generalize to left occipitotemporal regions neighbouring the VWFA. In addition, we demonstrated that these functional connections between the VWFA and other major language areas are disrupted in children with dyslexia, whereas those of neighbouring areas were not affected. The results of both studies reveal an impairment of both function (of the VWF-system) and functional connectivity (of the VWFA with left inferior parietal and inferior frontal cortex) in dyslexic children. In conclusion, the findings presented in this work demonstrate that (1) word processing deficits in dyslexic children are associated with a pervasive developmental dysfunction of the entire VWF-system, and that (2) brain regions necessary for fluent, skilled reading may not work together properly during reading.