Biology subjects

Pieper, S.

Publications and source records attributed to Pieper, S..

6 recordsLinked to original sources

bioRxiv2025

The superficial white matter in language processing: Broca's area connections are bilaterally associated with individual performance in children and adults

While deeper white matter connections, such as the arcuate fasciculus and frontal aslant tract, are well known for their role in language and show leftward asymmetries in adults, the contribution of the short-range cortico-cortical superficial white matter (SWM) connections remains less understood. In this preregistered study, we examined white matter connections of Brocas area and its right hemisphere homolog in early adolescents and young adults using two large, publicly available datasets: the Adolescent Brain Cognitive Development Study and the Human Connectome Project Young Adult Study, totaling over 10,000 participants. We anatomically curated the ODonnell Research Group (ORG) tractography atlas to identify SWM fiber clusters intersecting Brocas area (pars opercularis and pars triangularis), confirmed through expert visual inspection. We investigated the microstructure, structural connectivity, and lateralization of Brocas area SWM and its relationship with language performance (Picture Vocabulary and Oral Reading Recognition assessments), in comparison to the deeper white matter connections of the frontal aslant tract and arcuate fasciculus. The arcuate fasciculus demonstrated the strongest and most consistent leftward lateralization of both microstructure (fractional anisotropy, FA) and structural connectivity (number of streamlines, NoS), with structure-function associations that were bilateral in adolescents and left-dominant in adults. Interestingly, despite weaker lateralization than the arcuate fasciculus, both the SWM and the frontal aslant tract demonstrated comparable associations with language performance. The frontal aslant tract showed greater leftward lateralization (FA and NoS) with age and was bilaterally associated with language performance, particularly in adolescents. Compared to these deeper tracts, Brocas area SWM demonstrated left-lateralized FA and right-lateralized NoS in both adolescents and adults, with stronger FA lateralization in adults. Bilateral SWM FA and NoS were significantly associated with language performance in both hemispheres and age groups. Overall, these results suggest that Brocas area SWM may support language in a more bilaterally distributed manner and highlight the importance of considering SWM connections in studies of language development and neurosurgical planning.

neuroscience↗

bioRxiv2025

Consistent cerebellar pathway-cognition associations across pre-adolescents & young adults: a diffusion MRI study of 9000+ participants

The cerebellum, long implicated in movement, is now recognized as a contributor to higher-order cognition. The cerebellar pathways provide key structural links between the cerebellum and cerebral regions integral to language, memory, and executive function. Here, we present a large-scale, cross-sectional diffusion MRI (dMRI) analysis investigating the relationships between cerebellar pathway microstructure and cognitive performance in over 9,000 participants spanning pre-adolescence (n>8,000 from the ABCD dataset) and young adulthood (n>900 from the HCP-YA dataset). We assessed the microstructure of five cerebellar pathways--the inferior, middle, and superior cerebellar peduncles; the parallel fibers; and input/Purkinje fibers--using three dMRI measures of fractional anisotropy, mean diffusivity, and number of streamlines. Cognitive performance was evaluated using seven NIH Toolbox assessments of language, executive function, and memory. In both datasets, we found numerous significant associations between cerebellar pathway microstructure and cognitive performance. These associations showed a strong correlation across the two datasets (r = 0.47, p < 0.0001), underscoring the reliability of cerebellar dMRI-cognition relationships in pre-adolescents and young adults. In both datasets, the strongest associations were found between the superior cerebellar peduncle and performance on language assessments, suggesting this pathway plays an important role in language function across age groups. In young adults, but not pre-adolescents, parallel fiber microstructure was linked to inhibitory control, suggesting that contributions to attentional processes may emerge or strengthen with maturation. Overall, our findings highlight the important role of cerebellar pathways in cognition and the utility of large-scale datasets for advancing our understanding of brain-cognition relationships. SignificanceThis study provides strong evidence linking cerebellar pathway tissue microstructure to cognition across large populations of preadolescent children and young adults. By leveraging diffusion MRI tractography and cognitive performance data from two major datasets, we identify significant relationships between cerebellar pathway microstructure and cognitive performance. Importantly, findings are significantly correlated across datasets, pointing to the consistency of these relationships, bridging age groups and acquisitions. These results highlight the cerebellar pathways integral role in cognitive functioning and underscore the value of large-scale, population-based studies in advancing our understanding of brain-cognition relationships. Classification 1) Biological Sciences, Neuroscience; 2) Social Sciences, Psychological and Cognitive Sciences

neuroscience↗

bioRxiv2023

Harmonized diffusion MRI data and white matter measures from the baseline Adolescent Brain Cognitive Development (ABCD) study

The Adolescent Brain Cognitive Development (ABCD) study has collected data from over 10,000 children across 21 sites, providing valuable insights into adolescent brain development. However, site-specific scanner variability has made it challenging to use diffusion MRI (dMRI) data from this study. To address this, a database of harmonized and processed ABCD dMRI data has been created, comprising quality-controlled imaging data from 9345 subjects. This resource required significant computational effort, taking [~]50,000 CPU hours to harmonize the data, perform white matter parcellation, and run whole brain tractography. The database includes harmonized dMRI data, 800 white matter clusters, 73 anatomically labeled white matter tracts both in full-resolution (for analysis) and low-resolution (for visualization), and 804 different dMRI-derived measures per subject. It is available via the NIMH Data Archive and offers tremendous potential for scientific discoveries in structural connectivity studies of neurodevelopment in children and adolescents. Additionally, several post-harmonization experiments were conducted to demonstrate the success of the harmonization process on the ABCD dataset.

neuroscience↗

bioRxiv2020

SlicerMorph: An open and extensible platform to retrieve, visualize and analyze 3D morphology

Large scale digitization projects such as #ScanAllFishes and oVert are generating high-resolution microCT scans of vertebrates by the thousands. Data from these projects are shared with the community using aggregate 3D specimen repositories like MorphoSource through various open licenses. MorphoSource currently hosts tens of thousands of 3D scans of eukaryotes. Along with the data from similarly scoped projects such as 10kPhenomes, DigiMorph and many others, soon hundreds of thousands of specimens that represent biodiversity of extinct and extant organisms will be conveniently available to researchers. We anticipate an explosion of quantitative research in organismal biology with the convergence of available data and the methodologies to analyze them. Though the data are available, the road from a series of images to analysis is fraught with challenges for most biologists. It involves tedious tasks of data format conversions, preserving spatial scale of the data accurately, 3D visualization and segmentations, acquiring measurements and annotations. When scientists use commercial software with proprietary formats, a roadblock for data exchange, collaboration, and reproducibility is erected that hurts the efforts of the scientific community to broaden participation in research. Another relevant concern is that ultimate derivative data from individual research projects (e.g., 3D models of segmentation) are shared in formats that do not preserve the correct spatial scale of the data. In this paper, we present our effort to tackle challenges biologists face when conducting 3D specimen-based research. We developed SlicerMorph as an extension of 3D Slicer, a biomedical visualization and analysis ecosystem with extensive visualization and segmentation capabilities built on proven python-scriptable open-source libraries such as Visualization Toolkit and Insight Toolkit. In addition to the core functionalities of Slicer, SlicerMorph provides users with modules to conveniently retrieve open-access 3D models or import users own 3D volumes, to annotate 3D curve and patch-based landmarks, generate canonical templates, conduct geometric morphometric analyses of 3D organismal form using both landmark-driven and landmark-free approaches, and create 3D animations from their results. We highlight how these individual modules can be tied together to establish complete workflow(s) from image sequence to morphospace. Our software development efforts were supplemented with short courses and workshops that cover the fundamentals of 3D imaging and morphometric analyses as it applies to study of organismal form and shape in evolutionary biology, and extensive links to the existing tutorials are provided as supplemental material. Our goal is to establish a community of organismal biologists centered around Slicer and SlicerMorph to facilitate easy exchange of data and results and collaborations using 3D specimens. Our proposition to our colleagues is that using a common open platform supported by a large user and developer community ensures the longevity and sustainability of the tools beyond the initial development effort.

evolutionary biology↗

bioRxiv2019

Doxorubicin-loaded human serum albumin nanoparticles overcome transporter-mediated drug resistance

Resistance to systemic drug therapies is a major reason for the failure of anti-cancer therapies. Here, we tested doxorubicin-loaded human serum albumin (HSA) nanoparticles in the neuroblastoma cell line UKF-NB-3 and its ABCB1-expressing sublines adapted to vincristine (UKF-NB-3rVCR1) and doxorubicin (UKF-NB-3rDOX20). Doxorubicin-loaded nanoparticles displayed increased anti-cancer activity in UKF-NB-3rVCR1 and UKF-NB-3rDOX20 cells relative to doxorubicin solution, but not in UKF-NB-3 cells. UKF-NB-3rVCR1 cells were resensitised by nanoparticle-encapsulated doxorubicin to the level of UKF-NB-3 cells. UKF-NB-3rDOX20 cells displayed a more pronounced resistance phenotype than UKF-NB-3rVCR1 cells and were not re-sensitised by doxorubicin-loaded nanoparticles to the level of parental cells. ABCB1 inhibition using zosuquidar resulted in similar effects like nanoparticle incorporation, indicating that doxorubicin-loaded nanoparticles circumvent ABCB1-mediated drug efflux. The limited re-sensitisation of UKF-NB-3rDOX20 cells to doxorubicin by circumvention of ABCB1-mediated efflux is probably due to the presence of multiple doxorubicin resistance mechanisms. So far, ABCB1 inhibitors have failed in clinical trials, probably because systemic ABCB1 inhibition results in a modified body distribution of its many substrates including drugs, xenobiotics, and other molecules. HSA nanoparticles may provide an alternative, more specific way to overcome transporter-mediated resistance.

pharmacology and toxicology↗

bioRxiv2018

Incorporation of doxorubicin in different polymer nanoparticles and their anti-cancer activity

Nanoparticles are under investigation as carrier systems for anti-cancer drugs. They have been shown to accumulate in cancer tissues through the enhanced permeability and retention (EPR) effect, to reduce toxicity to non-target tissues, and to protect drugs from preliminary inactivation. However, nanoparticle preparations are not commonly compared for their anti-cancer effects at the cellular level. Here, we prepared doxorubicin-loaded nanoparticles based on poly(lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), and PEGylated PLGA (PLGA-PEG) by solvent displacement and emulsion diffusion approaches. The resulting nanoparticles covered a size range between 73 and 246 nm. PLGA-PEG nanoparticle preparation by solvent displacement resulted in the smallest nanoparticles. In PLGA nanoparticles, the drug load could be optimised using solvent displacement at pH7 reaching 53 {micro}g doxorubicin/mg nanoparticle. In addition, these PLGA nanoparticles displayed sustained doxorubicin release kinetics compared to the more burst-like kinetics of the other preparations. In neuroblastoma cells, doxorubicin-loaded PLGA-PEG nanoparticles (presumably due to their small size) and PLGA nanoparticles prepared by solvent displacement at pH7 (presumably due to their high drug load and superior drug release kinetics) exerted the strongest anti-cancer effects. In conclusion, doxorubicin-loaded nanoparticles made by different methods from different materials displayed substantial discrepancies in their anti-cancer activity at the cellular level. Optimised preparation methods resulted in PLGA nanoparticles characterised by increased drug load, controlled drug release, and high anti-cancer efficacy. The design of drug-loaded nanoparticles with optimised anti-cancer activity at the cellular level is an important step in the development of improved nanoparticle preparations for anti-cancer therapy.

pharmacology and toxicology↗