Biology subjects

Northall, A.

Publications and source records attributed to Northall, A..

5 recordsLinked to original sources

bioRxiv2023

Age-Related Differences in Human Cortical Microstructure Depend on the Distance to the Nearest Vein

Age-related differences in cortical microstructure are used to understand the neuronal mechanisms that underlie human brain ageing. The cerebral vasculature contributes to cortical ageing, but its precise interaction with cortical microstructure is poorly understood. In a cross-sectional study, we combine venous imaging with vessel distance mapping (VDM) to investigate the interaction between venous distances and age-related differences in the microstructural architecture of the primary somatosensory cortex (S1), the primary motor cortex (M1), and additional areas in frontal cortex as non-sensorimotor control regions. We scanned 18 younger adults and 17 older adults using 7T-MRI to measure age-related changes in quantitative T1 (qT1) values, positive QSM (pQSM) values, and negative QSM (nQSM) values at 0.5 mm isotropic resolution. We modelled different cortical depths using an equi-volume approach and assessed the distance of each voxel to its nearest vein using VDM. Our data reveal a dependence of cortical qT1 and pQSM values on venous distance. In addition, there is an interaction between venous distance and age on qT1 values, driven by lower qT1 values in older compared to younger adults in voxels that are closer to a vein. Together, our data show that the local venous architecture explains a significant amount of variance in standard measures of cortical microstructure and should be considered in neurobiological models of human brain organisation and cortical ageing.

neuroscience↗

bioRxiv2023

A layer-specific model of cortical sensory aging

The segregation of processes into cortical layers is a convergent feature in animal evolution. However, how changes in the cortical layer architecture interact with sensory system function and dysfunction remains unclear. We conducted functional and structural layer-specific in-vivo 7T-MRI of the primary somatosensory cortex in two cohorts of healthy younger and older adults. Input layer IV is enlarged and more myelinated in older adults, and associated with extended sensory input signals. Age-related cortical thinning is driven by deep layers and accompanied by increased myelination, but there is no clear evidence for reduced inhibition. Calcium imaging and histology in younger and older mice reveal increased sensory-evoked neuronal activity accompanied by increased parvalbumin expression as a potential inhibitory balance, with dynamic changes in layer-specific myelination across age groups. Using multimodal imaging, we demonstrate that middle and deep layers show specific sensitivity to aging across species.

neuroscience↗

bioRxiv2023

Multimodal layer modeling reveals in-vivo pathology in ALS

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease characterised by the loss of motor control. Current understanding of ALS pathology is largely based on post-mortem investigations at advanced disease stages. A systematic in-vivo description of the microstructural changes that characterise early-stage ALS, and their subsequent development, is so far lacking. Recent advances in ultra-high field (7T) MRI data modelling allow us to investigate cortical layers in-vivo. Given the layer-specific and topographic signature of pathology in ALS, we combined submillimeter structural 7T-MRI data (qT1, QSM), functional localisers of body parts (upper limb, lower limb, face) and automated layer modelling to systematically describe pathology in the primary motor cortex (M1), in 12 living ALS-patients with reference to 12 age-, gender-, handedness- and education-matched controls. Longitudinal sampling was performed for a subset of patients. We calculated multimodal pathology maps for each layer (superficial layer, layer 5a, layer 5b, layer 6) of M1 to identify hotspots of demyelination, iron and calcium accumulation in different cortical fields. We show preserved mean cortical thickness and layer architectures of M1, despite significantly increased iron in layer 6 and significantly increased calcium in layer 5a and superficial layer, in patients compared to controls. The behaviorally first-affected cortical field shows significantly increased iron in L6 compared to other fields, while calcium accumulation is atopographic and significantly increased in the low-myelin borders between cortical fields compared to the fields themselves. A subset of patients with longitudinal data shows that the low-myelin borders are particularly disrupted, and that calcium hotspots but to a lesser extent iron hotspots precede demyelination. Finally, we highlight that a very-slow progressing patient (P4) shows a distinct pathology profile compared to the other patients. Our data shows that layer-specific markers of in-vivo pathology can be identified in ALS-patients with a single 7T-MRI measurement after first diagnosis, and that such data provide critical insights into the individual disease state. Our data highlight the non-topographic architecture of ALS disease spread, and the role of calcium rather than iron accumulation in predicting future demyelination. We also highlight a potentially important role of low-myelin borders, that are known to connect to multiple areas within the M1 architecture, in disease spread. Importantly, the distinct pathology profile of a very-slow progressing patient (P4) highlights a distinction between disease duration and pathology progression. Our findings demonstrate the importance of in-vivo histology for the diagnosis and prognosis of neurodegenerative diseases such as ALS.

neuroscience↗

bioRxiv2022

The 3D Structural Architecture of the Human Hand Area is Non-Topographic

The functional topography of the human primary somatosensory cortex (S1) hand area is a widely studied model system to understand sensory organization and plasticity. It is so far unclear whether or not the underlying 3D structural architecture also shows a topographic organization. We used 7T MRI data to quantify layer-specific myelin, iron and mineralization in relation to population receptive field maps of individual finger representations in Brodman area 3b (BA 3b) of human S1 in female and male younger adults. This 3D description allowed us to identify a characteristic profile of layer-specific myelin and iron deposition in the BA 3b hand area, but revealed an absence of structural differences, an absence of low-myelin borders, and high similarity of 3D microstructure profiles between individual fingers. However, structural differences and borders were detected between the hand and face areas. We conclude that the 3D structural architecture of the human hand area is non-topographic, unlike in some monkey species, which suggests a high degree of flexibility for functional finger organization and a new perspective on human topographic plasticity. Significance StatementUsing ultra-high field MRI, we provide the first comprehensive in vivo description of the 3D structural architecture of the human BA 3b hand area in relation to functional population receptive field (pRF) maps. High similarity of precise finger-specific 3D profiles, together with an absence of structural differences and an absence of low-myelin borders between individual fingers, reveal the 3D structural architecture of the human hand area to be non-topographic. This suggests reduced structural limitations to cortical plasticity and reorganization, and allows for shared representational features across fingers.

neuroscience↗

bioRxiv2022

Topographic Stability and Layer-Specific Flexibility are Mechanisms of Human Cortical Plasticity

Topographic maps form a critical feature of cortical organization, yet are poorly described with respect to their microstructure in the living aging brain. We acquired quantitative structural and functional 7T-MRI data from younger and older adults to characterize layer-wise topographic maps of the primary motor cortex (M1). Using parcellation-inspired techniques, we show that qT1 and QSM values of the hand, face, and foot areas differ significantly, revealing microstructurally-distinct cortical fields in M1. We show that these fields are distinct in older adults, and that myelin borders between them do not degenerate. We further show that the output layer 5 of M1 shows a particular vulnerability to age-related increased iron, while layer 5 and the superficial layer show increased diamagnetic substance, likely reflecting calcifications. Taken together, we provide a novel 3D model of M1 microstructure, where body parts form distinct structural units, but layers show specific vulnerability towards increased iron and calcium in older adults. Our findings have implications for understanding sensorimotor organization and aging, in addition to topographic disease spread.

neuroscience↗