Biology subjects

Mezzano, S.

Publications and source records attributed to Mezzano, S..

3 recordsLinked to original sources

bioRxiv2026

Mapping reward processing circuits: the orbitofrontal-nucleus accumbens white matter pathways and their associations to psychopathological traits

Dysfunctions in reward circuits, including projections from the orbitofrontal cortex (OFC) to the nucleus accumbens (NAcc), have been implicated in psychopathology. The OFC is functionally divided into the medial OFC (mOFC), which processes rewards, and the lateral OFC (lOFC), which responds to non-reward or punishment stimuli. We investigated the structural connectivity of the lOFC-NAcc and mOFC-NAcc pathways and their associations with psychopathological traits using tractography-defined ROI analysis. Diffusion-weighted imaging data from 165 participants (aged 22 - 35, 53% male) in the Human Connectome Project (HCP) were analysed using spherical deconvolution tractography. MegaTrack, a novel tool, enabled tract segmentation via a single manual dissection mapped back to native space. Virtual dissection identified four bilateral pathways connecting the lOFC and mOFC to the NAcc, from which fractional anisotropy (FA) was extracted, and an lOFC/mOFC ratio was computed. Psychopathological traits were measured using HCP Achenbach Adult Self-Report scores. The lOFC-NAcc pathway showed positive associations with psychopathology and the mOFC-NAcc pathway negative associations. The lOFC/mOFC ratio emerged as a stronger predictor than individual pathways, with significant associations for depression, somatic problems, anti-social personality traits, and inattention. Effects were lateralized to the left hemisphere. These findings show that the lOFC-NAcc and mOFC-NAcc pathways can be structurally separated with tractography and display opposing correlations with psychopathological traits in a healthy population. Their ratio may index reward-processing dysfunction, and future research should test whether it is sensitive to dysfunction in clinical populations.

neuroscience↗

bioRxiv2025

Microstructural correlates of white and gray matter in the healthy human brain: comparative analysis of diffusion biophysical models, inhomogeneous magnetization transfer, and macromolecular proton fraction

Abstract summaryDiffusion MRI (dMRI) and magnetization transfer (MT) rely on distinct biophysical principles and provide complementary insights into tissue microstructure. In this study, we investigated associations between microstructural metrics derived from the Standard Model (SMI) in white matter (WM) and the Standard Model with EXchange (SMEX/NEXI) in gray matter (GM) with two MT measures differing in specificity and sensitivity to myelination: the macromolecular proton fraction (MPF) and the inhomogeneous magnetization transfer ratio (ihMTR). Measurements were performed in WM and GM in ten healthy subjects scanned at 3T. In WM, the strongest significant association was observed between ihMTR and the axonal water fraction, consistent with higher myelination in regions of elevated axonal density and limited extra-axonal space. This correlation exceeded that of MPF, supporting the greater specificity of ihMTR to myelin. Interestingly, ihMTR displayed a gradient along the longitudinal axis of the corpus callosum, in agreement with previous histology measurements. Correlation between ihMTR and the extra-axonal perpendicular diffusivity (De{perp}), a putative myelination biomarker, was not significant, whereas MPF and De{perp} exhibited a moderate significant positive correlation. Since a negative correlation is expected if reflecting myelination, these results suggest that in healthy tissue De{perp} is mainly influenced by microstructural factors like fiber coherence and packing, the latter most likely affecting MPF but not ihMTR. In GM, ihMTR correlated significantly only with the exchange time (t), confirming tex as a proxy for cell membrane permeability modulated by myelin. MPF correlated exclusively with the cell-process fraction (f), suggesting the latter is modulated by total (neuronal and glial) cell membrane density. Overall, findings underscore the complementary and concurring microstructural information captured by these metrics, highlighting their potential to disentangle distinct tissue mechanisms in both healthy and pathological conditions. Future studies incorporating ground-truth histology should validate the precise sensitivity of each metric to various microstructural tissue features.

neuroscience↗

bioRxiv2025

Comparative Systematic Analysis of Gray Matter BiophysicalModels on a Public Dataset

Biophysical models of diffusion tailored to characterize gray matter (GM) microstructure are gaining traction in the neuroimaging community. NEXI, SMEX, SANDI, and SANDIX represent recent efforts to incorporate different microstructural features,such as soma contributions and inter-compartment exchange, into the diffusion MRI (dMRI) signal. In this work, we present a comparative evaluation of these four gray matter models on a single, publicly available in vivo human dataset, the Connectome Diffusion Microstructure Dataset (CDMD), acquired with two diffusion times. Using the open-source Gray Matter Swiss Knife toolbox, we estimate cortical microstructure metrics in 26 healthy subjects and evaluate goodness of fit, anatomical patterns and consistency with previous studies. CDMD data yielded GM parameter estimates consistent with values reported in previous studies. This retrospective cross-model analysis establishes the feasibility of estimating exchange models from only two diffusion times and highlights trade-offs in biological specificity, model complexity, and fitting robustness, critical considerations when choosing a model for future clinical and research applications.

neuroscience↗