Micro-probing enables fine-grained mapping of neuronal populations using fMRI

The characterization of receptive field (RF) properties is fundamental to understanding the neural basis of sensory and cognitive behaviour. The combination of non-invasive imaging, such as fMRI, with biologically inspired neural modelling has enabled the estimation of population RFs directly in humans. However, current approaches require making numerous a priori assumptions, so these cannot reveal unpredicted properties, such as fragmented RFs or subpopulations. This is a critical limitation in studies on adaptation, pathology or reorganization. Here, we introduce micro-probing (MP), a technique for fine-grained and largely assumption free characterization of multiple pRFs within a voxel. It overcomes many limitations of current approaches by enabling detection of unexpected RF shapes, properties and subpopulations, by enhancing the spatial detail with which we analyze the data. MP is based on tiny, fixed-size, Gaussian models that efficiently sample the entire visual space and create fine-grained probe maps. Subsequently, we derived population receptive fields (pRFs) from these maps. We demonstrate the scope of our method through simulations and by mapping the visual fields of healthy participants and of a patient group with highly abnormal RFs due to a congenital pathway disorder. Without using specific stimuli or adapted models, MP mapped the bilateral pRFs characteristic of observers with albinism. In healthy observers, MP revealed that voxels may capture the activity of multiple subpopulations RFs that sample distinct regions of the visual field. Thus, MP provides a versatile framework to visualize, analyze and model, without restrictions, the diverse RFs of cortical subpopulations in health and disease.</p

Associations of CSF PDGFRβ With Aging, Blood-Brain Barrier Damage, Neuroinflammation, and Alzheimer Disease Pathologic Changes

BACKGROUND AND OBJECTIVES: Injured pericytes in the neurovascular unit release platelet-derived growth factor β (PDGFRβ) into the CSF. However, it is not clear how pericyte injury contributes to Alzheimer disease (AD)-related changes and blood-brain barrier (BBB) damage. We aimed to test whether CSF PDGFRβ was associated with different AD-associated and age-associated pathologic changes leading to dementia. METHODS: PDGFRβ was measured in the CSF of 771 participants with cognitively unimpaired (CU, n = 408), mild cognitive impairment (MCI, n = 175), and dementia (n = 188) from the Swedish BioFINDER-2 cohort. We then checked association with β-amyloid (Aβ)-PET and tau-PET standardized uptake value ratio, APOE ε4 genotype and MRI measurements of cortical thickness, white matter lesions (WMLs), and cerebral blood flow. We also analyzed the role of CSF PDGFRβ in the relationship between aging, BBB dysfunction (measured by CSF/plasma albumin ratio, QAlb), and neuroinflammation (i.e., CSF levels of YKL-40 and glial fibrillary acidic protein [GFAP], preferentially expressed in reactive astrocytes). RESULTS: The cohort had a mean age of 67 years (CU = 62.8, MCI = 69.9, dementia = 70.4), and 50.1% were male (CU = 46.6%, MCI = 53.7%, dementia = 54.3%). Higher CSF PDGFRβ concentrations were related to higher age (b = 19.1, β = 0.5, 95% CI 16-22.2, p 0.05). DISCUSSION: In summary, pericyte damage, reflected by CSF PDGFRβ, may be involved in age-related BBB disruption together with neuroinflammation, but is not related to Alzheimer-related pathologic changes

Triple visual hemifield maps in a case of optic chiasm hypoplasia

In humans, each hemisphere comprises an overlay of two visuotopic maps of the contralateral visual field, one from each eye. Is the capacity of the visual cortex limited to these two maps or are plastic mechanisms available to host more maps? We determined the cortical organization of the visual field maps in a rare individual with chiasma hypoplasia, where visual cortex plasticity is challenged to accommodate three hemifield maps. Using high-resolution fMRI at 7T and diffusion-weighted MRI at 3T, we found three hemiretinal inputs, instead of the normal two, to converge onto the left hemisphere. fMRI-based population receptive field mapping of the left V1-V3 at 3T revealed three superimposed hemifield representations in the left visual cortex, i.e. two representations of opposing visual hemifields from the left eye and one right hemifield representation from the right eye. We conclude that developmental plasticity including the re-wiring of local intra- and cortico-cortical connections is pivotal to support the coexistence and functioning of three hemifield maps within one hemisphere

Quantifying nerve decussation abnormalities in the optic chiasm

OBJECTIVE: The human optic chiasm comprises partially crossing optic nerve fibers. Here we used diffusion MRI (dMRI) for the in-vivo identification of the abnormally high proportion of crossing fibers found in the optic chiasm of people with albinism. METHODS: In 9 individuals with albinism and 8 controls high-resolution 3T dMRI data was acquired and analyzed with a set of methods for signal modeling [Diffusion Tensor (DT) and Constrained Spherical Deconvolution (CSD)], tractography, and streamline filtering (LiFE, COMMIT, and SIFT2). The number of crossing and non-crossing streamlines and their weights after filtering entered ROC-analyses to compare the discriminative power of the methods based on the area under the curve (AUC). The dMRI results were cross-validated with fMRI estimates of misrouting in a subset of 6 albinotic individuals. RESULTS: We detected significant group differences in chiasmal crossing for both unfiltered DT (p = 0.014) and CSD tractograms (p = 0.0009) also reflected by AUC measures (for DT and CSD: 0.61 and 0.75, respectively), underlining the discriminative power of the approach. Estimates of crossing strengths obtained with dMRI and fMRI were significantly correlated for CSD (R2 = 0.83, p = 0.012). The results show that streamline filtering methods in combination with probabilistic tracking, both optimized for the data at hand, can improve the detection of crossing in the human optic chiasm. CONCLUSIONS: Especially CSD-based tractography provides an efficient approach to detect structural abnormalities in the optic chiasm. The most realistic results were obtained with filtering methods with parameters optimized for the data at hand. SIGNIFICANCE: Our findings demonstrate a novel anatomy-driven approach for the individualized diagnostics of optic chiasm abnormalities

CHIASM, the human brain albinism and achiasma MRI dataset

We describe a collection of T1-, diffusion- and functional T2*-weighted magnetic resonance imaging data from human individuals with albinism and achiasma. This repository can be used as a test-bed to develop and validate tractography methods like diffusion-signal modeling and fiber tracking as well as to investigate the properties of the human visual system in individuals with congenital abnormalities. The MRI data is provided together with tools and files allowing for its preprocessing and analysis, along with the data derivatives such as manually curated masks and regions of interest for performing tractography

Structural changes to primary visual cortex in the congenital absence of cone input in achromatopsia

Autosomal recessive Achromatopsia (ACHM) is a rare inherited disorder associated with dysfunctional cone photoreceptors resulting in a congenital absence of cone input to visual cortex. This might lead to distinct changes in cortical architecture with a negative impact on the success of gene augmentation therapies. To investigate the status of the visual cortex in these patients, we performed a multi-centre study focusing on the cortical structure of regions that normally receive predominantly cone input. Using high-resolution T1-weighted MRI scans and surface-based morphometry, we compared cortical thickness, surface area and grey matter volume in foveal, parafoveal and paracentral representations of primary visual cortex in 15 individuals with ACHM and 42 normally sighted, healthy controls (HC). In ACHM, surface area was reduced in all tested representations, while thickening of the cortex was found highly localized to the most central representation. These results were comparable to more widespread changes in brain structure reported in congenitally blind individuals, suggesting similar developmental processes, i.e., irrespective of the underlying cause and extent of vision loss. The cortical differences we report here could limit the success of treatment of ACHM in adulthood. Interventions earlier in life when cortical structure is not different from normal would likely offer better visual outcomes for those with ACHM

Structural differences across multiple visual cortical regions in the absence of cone function in congenital achromatopsia

Most individuals with congenital achromatopsia (ACHM) carry mutations that affect the retinal phototransduction pathway of cone photoreceptors, fundamental to both high acuity vision and colour perception. As the central fovea is occupied solely by cones, achromats have an absence of retinal input to the visual cortex and a small central area of blindness. Additionally, those with complete ACHM have no colour perception, and colour processing regions of the ventral cortex also lack typical chromatic signals from the cones. This study examined the cortical morphology (grey matter volume, cortical thickness and cortical surface area) of multiple visual cortical regions in ACHM (n=15) compared to normally sighted controls (n=42) to determine the cortical changes that are associated with the retinal characteristics of ACHM. Surface-based morphometry was applied to T1-weighted MRI in atlas-defined early, ventral and dorsal visual regions of interest. Reduced grey matter volume in V1, V2, V3 and V4 was found in ACHM compared to controls, driven by a reduction in cortical surface area as there was no significant reduction in cortical thickness. Cortical surface area (but not thickness) was reduced in a wide range of areas (V1, V2, V3, TO1, V4 and LO1). Reduction in early visual areas with large foveal representations (V1, V2 and V3) suggests that the lack of foveal input to the visual cortex was a major driving factor in morphological changes in ACHM. However, the significant reduction in ventral area V4 coupled with the lack of difference in dorsal areas V3a and V3b suggest that deprivation of chromatic signals to visual cortex in ACHM may also contribute to changes in cortical morphology. This research shows that the congenital lack of cone input to the visual cortex can lead to widespread structural changes across multiple visual areas

Psychophysical evidence for impaired Magno, Parvo, and Konio-cellular pathways in dyslexic children

Purpose: Dyslexia is one of the most common learning disabilities affecting millions of people worldwide. Although exact causes of dyslexia are not well-known, a deficit in the magnocellular pathway may play a role. We examined possible deficiency of magnocellular, as compared to parvocellular and koniocellular pathway function by measuring luminance and color perception. Methods: Visual stimuli consisted of a series of natural images, divided into layers of luminance, red-green and blue-yellow, which probed magnocellular, parvocellular, and koniocellular pathways, respectively. Thirteen children with dyslexia and 13 sex- and age- matched controls performed three psychophysical tasks. In the first task, subjects were instructed to match the contrast of luminance (magno) and red-green (parvo) images to that of the blue-yellow (konio) images. In the second task, subjects detected the isoluminant point of red-green images to probe parvocellular pathway. In the third task, temporal processing was assessed by measuring reaction time and percentage of correct responses in an identification task using four categories of images, activating all three pathways. Results: The dyslexic group had significantly elevated luminance and color contrast thresholds and higher isoluminant point ratio in comparison to the control group. Furthermore, they had significantly less correct responses than the control group for the blue-yellow images. Conclusion: We may suggest that dyslexic subjects might suffer from both magnocellular and parvocellular deficits. Moreover, our results show partial impairment of the koniocellular pathway. Thus, dyslexia might be associated with deficits in all three visual pathways