Biology subjects

Sawiak, S.

Publications and source records attributed to Sawiak, S..

5 recordsLinked to original sources

bioRxiv2025

Cortical myelination networks reflect neuronal gene expression and track adolescent age in marmosets

Structural similarity provides a powerful framework for measuring coordinated macro- and microstructural variation across the cortex of a single brain. Similarity networks derived from myelin-sensitive MRI sequences undergo marked reorganisation during adolescence, linked to psychosocial outcomes in humans and rodents. However, the cellular mechanisms of myelination similarity and its development in non-human primate cortex remain unexplored. Here, we used myelin-sensitive T1w/T2w ratio images from a cross-sectional sample of 446 common marmosets (aged 0.62 to 12.75 years) to estimate cortical similarity networks in individual animals. Cortical areas with similar myeloarchitecture showed highly similar patterns of gene co-expression in glutamatergic neurons and PV+ and VIP+ interneurons, reflecting the activity dependence of myelination. A reliable age-based signal exists within network features, with coordinated developmental trajectories observed across the cortical hierarchy from primary to transmodal association cortices - a pattern that mirrors findings in human cortex. Taken together, marmosets demonstrate phylogenetically conserved patterns of myelination network development, potentially underpinned by key neuronal cell types that shape the functional specialisation of cortical areas.

neuroscience↗

bioRxiv2024

Multi-site Ultrashort Echo Time 3D Phosphorous MRSI repeatability using novel Rosette Trajectory (PETALUTE)

PurposeThis study aims 1) to implement an operator-independent acquisition, reconstruction, and processing pipeline using a novel rosette k-space pattern for UTE 31P 3D MRSI and 2) to evaluate the clinical applicability and replicability at different experimental setups. MethodsA multicenter repeatability study was conducted for the novel UTE 31P 3D Rosette MRSI at three institutions with different experimental setups. Non-localized 31P MRSI data of 5 healthy subjects at each site were acquired with an acquisition delay of 65 s and a final resolution of 10 x 10 x 10 mm3 in 9 min. Spectra were quantified using the LCModel package. The potential acceleration was achieved using compressed sensing on retrospectively undersampled data. Reproducibility at each site was evaluated using the inter-subject coefficient of variance. ResultsThis novel acquisition and advanced processing techniques yielded high-quality spectra and enabled the detection of the critical brain metabolites at three different sites with different hardware specifications. In vivo, feasibility with an acceleration factor of 4 in 6.75 min resulted in a mean Cramer-Rao lower bounds below 20% for PCr, ATPs, PME, and the mean CoV of ATP/PCr resulted in below %20. ConclusionWe demonstrated that UTE 31P 3D Rosette MRSI acquisition, combined with compressed sensing and LCModel analysis, allows patient-friendly, operator-independent, high-resolution 31P MRSI to be acquired at clinical setups.

neuroscience↗

bioRxiv2023

Neurodevelopmental timing and socio-cognitive development in a prosocial cooperatively breeding primate (Callithrix jacchus)

Primate, and especially human, brain development is experience-dependent: it is shaped by the inputs received during critical periods. During early development, these inputs systematically differ between independently and cooperatively breeding species, because in cooperative breeders infants are interacting from birth with multiple caretakers and have to thrive in a richer and more challenging social environment. Here, we study the neurodevelopmental timing of the cooperatively breeding common marmoset and how it maps onto behavioral and developmental milestones. To obtain meaningful correlations of structure-function co-constructions, we combine behavioral, imaging (anatomical and functional) and neural tracing experiments. We focus on brain areas that are critically involved when observing conspecifics interacting with others and find that (i) these areas develop in clusters; (ii) these areas reach their maximum gray matter volume shortly after peak provisioning, when immatures are intensely provisioned by group members; (iii) the differentiation of these areas coincides with the period of intense negotiation between immatures and multiple adults over food, the birth of the next set of siblings, and the task of becoming a helper. Moreover, like in humans, differentiation is not fully completed at the age of first reproduction. In sum, we find that the developmental timing of social brain areas coincides with key social and developmental milestones in marmosets, and extends into early adulthood. This rich social input is likely critical for the emergence of the particularly strong prosociality and socio-cognitive skills of marmosets. Since humans are cooperative breeders too, these findings have strong implications for the evolution of human social cognition.

neuroscience↗

bioRxiv2022

Neurobehavioral precursors of compulsive cocaine-seeking in dual fronto-striatal circuits

Only some individuals using drugs recreationally eventually become addicted, and persist in drug seeking and taking despite adverse consequences. The neurobehavioral determinants of this individual vulnerability have not been fully elucidated. We report that in drug naive rats the future tendency to develop compulsive cocaine seeking is characterised by behavioral stickiness-related functional hypoconnectivity between the prefrontal cortex and posterior dorsomedial striatum in combination with impulsivity-related structural alterations in the infralimbic cortex, anterior insula and nucleus accumbens. These findings show that the vulnerability to develop compulsive cocaine seeking behavior stems from pre-existing structural or functional changes in two distinct cortico-striatal systems that underlie deficits in impulse control and goal-directed behavior.

neuroscience↗

bioRxiv2020

MRI-guided histology of TDP-43 knock-in mice implicates parvalbumin interneuron loss, impaired neurogenesis and aberrant neurodevelopment in ALS-FTD

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are overlapping neurodegenerative diseases that are increasingly understood to have long prodromal periods. Investigation of these early stages promises to yield valuable biomarkers of disease and will be key to understanding mechanisms underlying the genesis of ALS-FTD. Here, we use in vivo magnetic resonance imaging (MRI), histology and computed tomography to identify structural and cellular readouts of early stage disease in the TDP-43Q331K knock-in mouse model of ALS-FTD. Adult mutant mice demonstrated parenchymal volume reductions affecting the frontal lobe and entorhinal cortex in a manner reminiscent of ALS-FTD. Subcortical, cerebellar and brain stem regions were also affected in line with observations in presymptomatic carriers of mutations in C9orf72, the commonest genetic cause of both ALS and FTD. Volume loss, as measured by MRI, was also observed in the dentate gyrus (DG) of the hippocampus, along with ventricular enlargement. Guided by these imaging findings, detailed post-mortem brain tissue analysis revealed reduced parvalbumin-positive (PV+) interneurons as a potential cellular correlate of MRI changes in mutant mice. By contrast, microglia were in a disease activated state even in the absence of brain volume loss. A reduction in immature neurons was found in the DG, indicative of impaired adult neurogenesis, while a paucity of PV+ interneurons in juvenile mutant mice (P14) suggests that TDP-43Q331K disrupts neurodevelopment. Computerised tomography imaging also showed altered skull morphology in mutants, further suggesting a role for TDP-43Q331K in development. Finally, analysis of human post-mortem prefrontal cortices confirmed a paucity of PV+ interneurons in the prefrontal cortex in cases with both sporadic ALS and ALS linked to C9orf72 mutations. This study suggests an important role for PV+ interneurons in regional brain vulnerability associated with ALS-FTD, and identifies novel MRI and histological biomarkers that will be of value in assessing the efficacy of putative therapeutics in TDP-43Q331K knock-in mice.

neuroscience↗