While diffusion MRI is typically used to estimate microstructural properties of tissue in volumetric elements (voxels), more specificity can be obtained by separately modelling the properties of individual fibre populations within a voxel. In the context of cross-subjects modelling, these fixel-based analyses are usually performed in two stages. Crossing fibre modelling is first performed in each subject to produce fixels, and these are subsequently modelled across subjects following registration and fibre population reassignment. Here, we introduce a new hierarchical framework for fitting crossing fibre models to diffusion MRI data in a population of subjects. This hierarchical setup guarantees that the crossing fibres are consistent by construction and, therefore, comparable across subjects. We propose an expectation-maximisation algorithm to fit the model, which can scale to large number of subjects. This approach produces a template for crossing fibre populations in the white matter which can be used to estimate fibre-specific parameters that are consistent across subjects, hence providing data that are by construction suitable for fixel-based statistical analyses.

Early childhood experience alters visual development, a process exemplified by amblyopia, a common neurodevelopmental condition resulting in cortically reduced vision in one eye. Visual deficits in amblyopia may be a consequence of abnormal suppressive interactions in the primary visual cortex by inhibitory neurotransmitter γ-aminobutyric acid (GABA). We examined the relationship between visual acuity loss and GABA+ in adult human participants with amblyopia. Single-voxel proton magnetic resonance spectroscopy (MRS) data were collected from the early visual cortex (EVC) and posterior cingulate cortex (control region) of 28 male and female adults with current or past amblyopia while they viewed flashing checkerboards monocularly, binocularly, or while they had their eyes closed. First, we compared GABA+ concentrations between conditions to evaluate suppressive binocular interactions. Then, we correlated the degree of visual acuity loss with GABA+ levels to test whether GABAergic inhibition could explain visual acuity deficits. Visual cortex GABA+ was not modulated by viewing condition, and we found weak evidence for a negative correlation between visual acuity deficits and GABA+. These findings suggest that reduced vision in one eye due to amblyopia is not strongly linked to GABAergic inhibition in the visual cortex. We advanced our understanding of early experience dependent plasticity in the human brain by testing the association between visual acuity deficits and visual cortex GABA in amblyopes of the most common subtypes. Our study shows that the relationship was not as clear as expected and provides avenues for future investigation.

Introduction: Functional magnetic resonance spectroscopy (fMRS) is a non-invasive technique for measuring dynamic changes in neurometabolites. While previous studies have observed concentration changes in metabolites during neural activation, the relationship between neurometabolite response and stimulus intensity and timing requires further investigation. To address this, we conducted an interleaved fMRS and functional magnetic resonance imaging (fMRI) experiment using a visual stimulus with varying contrast levels. Methods: A total of 20 datasets were acquired on a 7T MRI scanner. The visual task consisted of two STIM blocks (30 s/20 s ON/OFF, 4 min), with 10% or 100% contrast, interleaved with a 5 min REST block. A dynamic fitting approach was used for fMRS data analysis. For metabolite level changes, the STIM conditions were modeled in two different ways: either considering the full STIM block as active condition (full-block model) or only modeling the ON blocks as active condition (sub-block model). For linewidth changes due to the BOLD effect, STIM conditions were modeled using the sub-block model. Results: For both models, we observed significant increases in glutamate levels for both the 10% and 100% visual contrasts, but no significant difference between the contrasts. Decreases in aspartate, and glucose, and increases in total N-acetylaspartate and total creatine were also detected, although less consistently across both 10% and 100% visual contrasts. BOLD-driven linewidth decreases and fMRI-derived BOLD increases within the MRS voxel were observed at both 10% and 100% contrasts, with larger changes at 100% compared to 10% in the fMRI-derived BOLD only. We observed a non-linear relation between visual contrast, the BOLD response, and the glutamate response. Conclusion: Our study highlights the potential of fMRS as a complementary technique to BOLD fMRI for investigating the complex interplay between visual contrast, neural activity, and neurometabolism. Future studies should further explore the temporal response profiles of different neurometabolites and refine the statistical models used for fMRS analysis.