Functional Magnetic Resonance Spectroscopy (fMRS) study on reading-related metabolite changes : PhD thesis

Wasilewska, Katarzyna

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Functional Magnetic Resonance Spectroscopy (fMRS) study on reading-related metabolite changes : PhD thesis

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Title: Functional Magnetic Resonance Spectroscopy (fMRS) study on reading-related metabolite changes : PhD thesis

Abstract:

Functional Magnetic Resonance Spectroscopy (fMRS) is a non-invasive technique used to measure dynamic changes in metabolite concentrations in response to stimuli. Despite its potential for advancing our understanding of brain activation mechanisms, fMRS remains relatively novel and the temporal dynamics of glutamate (Glu), the main excitatory neurotransmitter, following stimulation have not yet been fully explored. To date, no studies have applied fMRS to the reading process, despite the potential of this approach to reveal dynamic glutamate responses that may underlie both typical reading and its impairments in dyslexia. One of the newest mechanistic account of dyslexia, the neural noise hypothesis, suggests that it could be caused by an imbalance between glutamate and gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter. In particular, an elevated concentration of glutamate in the left superior temporal sulcus (STS) was proposed to disrupt signal processing and impair reading acquisition. The aim of this thesis was to investigate glutamate concentration changes during reading-related tasks, in brain regions involved in reading: the superior temporal sulcus and the visual word form area (VWFA), as well as in one control region, the medial prefrontal cortex (mPFC). To characterize the temporal dynamics of glutamate, fMRS signals were acquired at four different delays between stimulus onset and signal acquisition. Participants with varying reading abilities, including individuals diagnosed with dyslexia and typical readers, were scanned at both 7T and 3T MR scanners. In total, 59 participants (29 with dyslexia, 13 females; 30 typical readers, 14 females) were scanned at 7T, and 40 participants (21 with dyslexia, 9 females; 19 typical readers, 11 females) at 3T. Glutamate levels were compared between groups to determine whether participants diagnosed with dyslexia exhibit higher glutamate concentrations in reading-related brain regions. While 7T scanners theoretically provide higher spectra resolution and improved metabolite separation, they also introduce technical challenges. For the VWFA, reliable analysis was not feasible due to insufficient spectral quality, highlighting the methodological difficulty of collecting data from regions susceptible to magnetic field inhomogeneities. In the STS, glutamate responses to reading-related stimulation were heterogeneous. Effects were more apparent in females, yet they were sensitive to blood oxygenated level depended (BOLD) correction and varied between 7T and 3T. No evidence of elevated glutamate in dyslexic participants within the left STS was observed, which does not support the neural noise hypothesis. Glutamate concentration changes were not limited to reading-sensitive regions, and some responses were also observed in the mPFC. A consistent glutamate response function could not be established, as glutamate changes varied across sex, group, brain region, stimulation type, and scanner. This inconsistency may reflect limited spectral quality due to a small number of averaged signals and the impact of BOLD contamination. Additionally, glutamate levels were significantly influenced by sex, age, and voxel tissue composition. While 7T improved some quality parameters, overall gains over 3T were inconsistent and region-dependent. These findings suggest that the practical advantages of ultra-high-field scanners in fMRS depend on region and are constrained by technical challenges.