Biology subjects

Mezer, A. A.

Publications and source records attributed to Mezer, A. A..

4 recordsLinked to original sources

bioRxiv2026

Sensorimotor basal ganglia circuit asymmetry explains lateralized motor dysfunction in early Parkinson's disease

Parkinsons disease (PD) is characterized by an early spatial pattern of degeneration in the basal ganglia. This pattern includes both posterior predominance and hemispheric asymmetry that correspond to lateralized motor symptoms. While these spatial features are well established in the striatum using dopaminergic imaging, it remains unclear whether they reflect local or circuit-level pathology across the broader basal ganglia system. It is also unknown whether widely available structural MRI can detect these spatial characteristics with comparable sensitivity. Here, we investigate the spatial pattern of basal ganglia pathology in harmonized clinical MRI data of 136 early-stage PD patients and 60 healthy controls from the PPMI database. Using gradient analyses, we identified anterior-posterior variations and selective posterior alterations in the putamen and external globus pallidus, revealing early subregional "PD hotspots". Hemispheric asymmetry analyses across the basal ganglia showed associations with motor symptom lateralization that were most substantial in the substantia nigra, posterior putamen, and posterior external globus pallidus, indicating preferential early involvement of the sensorimotor basal ganglia circuit in lateralized PD pathology. Joint models integrating multiple regions and MRI measurements approached the explanatory power of DaTSCAN and were consistent longitudinally. In addition, they achieved robust out-of-sample cross-validated motor asymmetry prediction across visits, providing non-redundant information beyond DaTSCAN. Together, our findings demonstrate that anatomically guided spatial analysis of routine MRI reveals subregional basal ganglia pathology that underlies motor symptom lateralization in PD. This study extends spatial characterization of the basal ganglia beyond the striatum and uncovers multiple regions and data-driven posterior "hotspots" that predict motor dysfunction asymmetry. Thus, this work advances the development of MRI-based circuit-level biomarkers of PD neurodegeneration.

neuroscience↗

bioRxiv2024

A qMRI approach for mapping microscopic water populations and tissue relaxivity in the in vivo human brain.

Quantitative magnetic resonance imaging (qMRI) enables non-invasive mapping of brain tissue microstructure and is widely used for monitoring various physiological and pathological brain processes. Here, we introduce a qMRI approach for enriching the microstructural characterization of the sub-voxel environment. Inspired by pioneering magnetization transfer (MT) models, this approach employs MT saturation to differentiate between various water populations within each voxel. Our in vivo results align well with theoretical predictions and are reproducible using standard qMRI protocols. We present an array of new quantitative maps, highlighting different aspects of the tissues water. Furthermore, by manipulating the effective water content and relaxation rate with MT, we approximate within the voxel the tissue relaxivity. This property reflects the dependency of R1 on the macromolecular tissue volume (MTV) and is associated with the lipid and macromolecular composition of the brain. Our approach also enables biophysically-informed modulation of the R1 contrast, resulting in a set of unique cortical profiles. Finally, we demonstrate the effectiveness of our technique in imaging the common pathology of white matter hyperintensities (WMH), revealing tissue degradation and molecular alterations.

neuroscience↗

bioRxiv2024

Multiparametric quantitative MRI uncovers putamen microstructural changes in Parkinson's Disease

Parkinsons disease (PD) is a progressive neurodegenerative disorder dominated by motor and non-motor dysfunction. Despite extensive research, the in vivo characterization of PD-related microstructural brain changes remains an ongoing challenge, limiting advancements in diagnostic and therapeutic strategies. The putamen, a critical structure within the basal ganglia, plays a key role in regulating movement and is profoundly affected in early PD-related neurodegeneration. In this study, we collected multiparametric quantitative MRI (qMRI) brain data of PD patients and healthy controls, to investigate microstructural alterations in the putamen in PD. We utilized a gradient analysis technique to analyze the spatial variations of various qMRI parameters, including relaxation rates (R1, R2, R2*), water fraction (WF), susceptibility, magnetization transfer saturation (MTsat), and diffusion metrics (MD, FA). Our findings reveal significant spatial gradients and interhemispheric asymmetries in these biophysical properties along the anterior-posterior axis of the putamen. Notably, PD patients exhibited increased water fraction and altered transverse relaxation rate R2*, particularly in the posterior putamen, correlated with motor symptom laterality. These microstructural changes suggest underlying tissue atrophy or neuroinflammatory processes associated with PD. The study underscores the importance of the posterior putamen as a focal point for PD pathology and highlights the potential of localized gradient analysis in detecting subtle yet clinically significant brain changes. The new qMRI dataset provides valuable insights into PD pathology, potentially aiding in the development of more precise diagnostic tools and targeted therapies.

neuroscience↗

bioRxiv2018

Modelling conduction delays in the corpus callosum using MRI-measured g-ratio

Conduction of action potentials along myelinated axons is affected by their structural features, such as the axonal g-ratio, the ratio between the inner and outer diameters of the myelin sheath surrounding the axon. The effect of g-ratio variance on conduction properties has been quantitatively evaluated using single-axon models. It has recently become possible to estimate a g-ratio weighted measurement in vivo using quantitative MRI. Nevertheless, it is still unclear whether the variance in the g-ratio in the healthy human brain leads to significant differences in conduction velocity. In this work we tested whether the g-ratio MRI measurement can be used to predict conduction delays in the corpus callosum. We present a novel framework in which the structural properties of fibers (i.e. length and g-ratio, measured using MRI), are incorporated in a biophysical model of axon conduction, to predict conduction delays of long-range white matter fibers. We applied this framework to the corpus callosum, and found conduction delay estimates that are compatible with previously estimated values of conduction delays. We account for the variance in the velocity given the axon diameter distribution in the splenium, mid-body and genu, to further compare the fibers within the corpus callosum. Conduction delays have been suggested to increase with age. Therefore, we investigated whether there are differences in the g-ratio and the fiber length between young and old adults, and whether this leads to a difference in conduction speed and delays. We found small but significant differences between the predicted delays of the two groups in the motor fibers of the corpus callosum. We also found that the motor fibers of the corpus callosum have the fastest conduction estimates. Using the axon diameter distributions, we found that the occipital fibers have the slowest estimations, while the frontal and motor fiber tracts have similar estimates. Our study provides a framework for predicting conduction latencies in vivo. The framework could have major implications for future studies of white matter diseases and large range network computations. Our results highlight the need for improving additional in vivo measurements of white matter microstructure.

neuroscience↗