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Theses

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Language recovery following stroke-related aphasia is highly variable. This makes it difficult to predict language recovery outcome in stroke patients. The hippocampus is a structure known to contribute to initial language learning, and it might play a role in language recovery. One possible way of measuring hippocampal function is by measuring its volume on structural MRI. We investigated whether the hippocampal volume and/or hippocampal subfield volumes of stroke patients are correlated with language recovery. We also investigated the additional predictive value of hippocampal (subfield) volume in language recovery, when combined with traditional predictors. We included 32 patients with post-stroke aphasia in this study. The patients received a structural MRI within one week following stroke. The hippocampal volume and hippocampal subfield volumes were calculated using the Hippocampal Subfields protocol on Freesurfer v6.0. Initial aphasia severity in the first week post-stroke was tested using a standardized diagnostic aphasia test (ScreeLing). To assess language recovery, we administered a standardized aphasic test on everyday verbal communication skills (ANELT) in the first week following stroke, and repeated the ANELT at four and nine months post-stroke. There was no significant correlation between the volume of the hippocampus or any of its subfields and ANELT scores in any phase post-stroke. Our results suggest that hippocampal volume in the acute phase post-stroke has no predictive value in the prognosis of language recovery following stroke. Further research is necessary to understand the potential role of the hippocampus in language recovery.

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This thesis focuses on the cognitive and neuroanatomical aspects of reading related subskills (such as phonology, orthography, speech perception and auditory processing) and on its dysfunction in dyslexia. The most prominent etiological theory on dyslexia postulates that the reading problems result from a phonological deficit, more specifically a deficit in the representation, storage and/or retrieval of speech sounds. It has been suggested that this phonological deficit is secondary to a more basic auditory deficit, but despite substantial research effort, the nature of these auditory problems remains hotly debated. A first controversy concerns the extent to which auditory problems in dyslexics are speech-specific, namely whether they can be reduced to basic auditory processing problems or whether they are phonetic in origin. A second topic of debate concerns the extent to which the auditory problems are specific to the processing of rapidly changing temporal information or whether they encompass a broader range of complex spectrotemporal processing. To address both questions within one test paradigm, we created a categorical perception task using four continua of similar acoustic complexity: (1) a speech contrast exploiting temporal cues (/ba/-/da/), (2) a speech contrast defined by non-temporal spectral cues (/u/-/y/), (3) a non-speech temporal contrast (spectrally rotated /ba/-/da/), and (4) a non-speech non-temporal contrast (spectrally rotated /u/-/y/). This design was first applied in an adult sample of 31 normal and 31 dyslexic readers (manuscript 1), and later in a 11-year old sample of 25 normal and 13 dyslexic readers (manuscript 2). In both studies, dyslexic readers demonstrate a specific deficit in the /bA/-/dA/ and rotated /bA/-/dA/-condition, which indicates a deficit in processing rapidly changing auditory information which is not speech-specific. At the neural level, it might be that these temporal specific processing problems are rooted in a decreased myelination, since this is crucial for a fast transmission of action potentials. Diffusion Tensor Imaging (DTI) provides a unique tool to non-invasively measure white matter properties, reflecting indirectly the degree of myelination. In addition, DTI also enables a 3D-reconstruction of white matter connections which is of particular interest to reading since this involves a widespread network of distant brain regions. The most consistent finding across previous DTI studies is that white matter integrity in the left temporoparietal region relates to reading and is decreased in dyslexic readers (review and meta-analysis in manuscript 3). However, evidence is sparse on which white matter bundle corresponds to this and how it relates to reading underlying subskills. We therefore conducted a DTI-study in the 20 best normal reading and 20 poorest dyslexic reading adults of manuscript 1 to investigate specific white matter tracts in relation to phonological and orthographic processing (manuscript 4). Results indicate that dyslexic adults show a lower white matter integrity in the left dorsal arcuate fasciculus, which correlates with phonological processes, whereas no deficit is observed in the left ventral inferior-fronto-occipital-fasciculus, which relates to orthographic aspects of reading. Finally, in manuscript 5 we focus on white matter correlates of auditory temporal processing by linking the DTI-data to neurofunctional EEG-coherence measures of slow (i.e. 4Hz) and fast (i.e. 20Hz) modulations. Dyslexic readers display relative to normal readers a lower neurofunctional coherence for 20 Hz modulations as well as a decreased left lateralization of white matter integrity in the arcuate fasiculus and in the posterior part of the superior temporal gyrus. Interestingly, left lateralization in the latter white matter region correlates in typical readers with better coherence on the fast modulation (20 Hz) whereas this relation was opposite in dyslexic readers. To conclude, at the cognitive level our dyslexic participants displayed specific problems in processing rapidly changing auditory information, which might correspond at the neural level to a decreased left dominance of white matter integrity in the auditory and language regions. The well known phonological problems of dyslexic readers seem to be reflected in a lower white matter integrity of the left arcuate fasciculus, whereas the inferior-fronto-occipital-fasciculus, involved in orthographic processing, is intact in dyslexic adults.

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Reading skills are essential to participate in modern-day society. The acquisition of reading skills is a dynamic process involving several behavioral and neural processes that are influenced by genetic and environmental factors. Although this multifactorial etiology is widely recognized, the interplay between levels across reading development remains poorly understood. New insights in relations between the different levels across time can advance theoretical understanding of reading development. In turn, this can lead to improved support for struggling readers and diminished negative repercussions of reading difficulties on mental wellbeing and broader academic achievement. With the current dissertation, we aimed to contribute to the field by extending our knowledge of some of the possible interrelations between behavioral, neural, familial and environmental factors across early reading development. A total of 162 Dutch-speaking children, of whom the majority had an increased family and/or cognitive risk for reading difficulties, were followed up from the pre-reading stage (kindergarten) until third grade. We showed that auditory and speech processing as well as auditory cortex structure in the pre-reading stage can predict later reading outcome, independent of familial risk for reading difficulties. When examined simultaneously with phonological processing though, speech processing showed a cascading effect on phonological awareness and consequently on reading. In light of the COVID-19 pandemic, we also looked at the influence of a critical change in the environment (school closures) on the development of phonological awareness and white matter plasticity in the reading network. Although unexpected, we did not find evidence for a negative impact of the school closures. We did, however, find a scanner-related difference in white matter integrity, which provides a cautionary tale for researchers wanting to set up much-needed neuroimaging collaborations. Although generalization to the population as a whole is limited, the findings of this dissertation have contributed to the theoretical understanding of reading development. Increasing understanding further will be pivotal to fine-tune identification and intervention strategies for struggling readers and to improve individual and societal outcomes.