Biology subjects

Lipp, I.

Publications and source records attributed to Lipp, I..

9 recordsLinked to original sources

bioRxiv2026

Evolution of the motor cortex microstructure and its lateralization: a comparative study of chimpanzees and humans

Human hand coordination exceeds that of other species, including great apes, and is marked by pronounced right-hand dominance. This specialization parallels an expansion of its cortical representation, forming the hand-knob in the motor cortex. In humans, this region shows high myelination on quantitative MRI (qMRI), but whether this feature is shared with great apes remains unclear. It is also unknown whether increased right-hand dominance in humans is mirrored by greater hemispheric asymmetry in cortical microstructure. Using high-resolution qMRI, we compared motor cortex subdivisions controlling the leg, hand, and face in humans and chimpanzees. We found consistently higher myelin and iron content in the hand-knob in both species, suggesting an evolutionarily conserved role. However, only humans showed enhanced rightward lateralization. These results highlight both conserved and species-specific features of the motor cortex, offering insights into the evolution of manual dexterity and handedness.

neuroscience↗

bioRxiv2026

Single-cell quantification of the iron-neuromelanin balance in dopaminergic neurons across the lifespan

Dopaminergic neurons in the substantia nigra depend on iron for dopamine synthesis but are vulnerable to iron-induced oxidative stress. Many of these neurons synthesize neuromelanin, an iron-chelating pigment that accumulates across the lifespan and makes them vulnerable in Parkinsons disease. It remains unclear whether their selective vulnerability arises from neuromelanin overload or from the release of toxic labile iron from the oversaturated pigment. We quantified iron and neuromelanin at the single-cell level across the lifespan of chimpanzees, a species closely resembling humans in pigment and iron accumulation. Combining quantitative MRI, X-ray fluorescence imaging, and microscopic colorimetry, we found that the iron-to-neuromelanin ratio remains stable with age across large neuronal populations. Chemical equilibrium modeling of the iron binding in neuromelanin indicated that cytosolic labile iron concentrations remain low throughout adulthood. We have found no evidence for neuromelanin saturation or increased iron-mediated toxicity with age. This finding challenges the hypothesis that neuromelanin saturation drives age-related dopaminergic vulnerability. The presented method provides a quantitative framework for studying iron homeostasis in these neurons.

neuroscience↗

bioRxiv2026

Thalamic Nuclei Functional Controllability Accounts for Cognitive Impairment in Multiple Sclerosis Over and Above Structural Damage

BackgroundThe thalamus has emerged as a key region involved in cognitive dysfunction in multiple sclerosis (MS). While previous studies have identified associations between thalamic structural damage, altered functional connectivity, and cognitive performance, the specific contributions of individual thalamic nuclei and the added value of integrating structural and functional metrics remain poorly understood. MethodsT1-weighted MRI, diffusion MRI, resting-state fMRI, and neuropsychological data were collected from 102 individuals with MS and 27 healthy controls. Thalamic grey matter volume, white matter microstructural integrity, and functional controllability were calculated for each nucleus and compared between individuals with MS and healthy controls, as well as between MS cognitive subgroups. Partial Spearman correlations were used to examine the relationship between imaging metrics across the three modalities, and also between imaging metrics and cognitive performance in MS. Sparse canonical correlation analysis models were used to examine the covariance between thalamic imaging metrics and cognitive performance in MS. ResultsWidespread atrophy and microstructural damage were observed across all thalamic nuclei in individuals with MS, regardless of cognitive status. In contrast, alterations in functional controllability were more spatially specific, primarily affecting the medial dorsal anterior nuclei, and were most pronounced in cognitively impaired individuals. These functional controllability metrics were independent of grey matter volume, white matter integrity, and lesion load. Combining thalamic functional controllability with structural metrics yielded a stronger association with cognitive performance in MS than either modality alone. ConclusionThis study provides novel evidence that functional controllability in the thalamus, particularly within the medial dorsal anterior nuclei, plays a critical role in cognitive impairment in MS. By applying a network control framework, our findings offer a dynamic systems perspective that extends beyond traditional connectivity analyses, capturing the thalamuss role in supporting flexible cognitive transitions. The integration of structural and functional controllability metrics enhances the ability to characterise individual differences in cognitive performance and may inform future efforts to identify biomarkers of cognitive dysfunction in MS.

neuroscience↗

bioRxiv2024

Lifespan trajectory of chimpanzee brains characterized by magnetic resonance imaging histology

Chimpanzee brain maturation provides an invaluable framework for understanding the evolution of the human brain. We performed ultra-high resolution quantitative magnetic resonance imaging (qMRI) with histological validation on post mortem brains from captive and wild chimpanzees with a broad age range. We mapped developmental myelination and age-related iron accumulation across regions and layers of the neocortex. Compared to humans, chimpanzees showed more myelination and iron deposition in motor and premotor cortices, while the auditory cortex was more strongly myelinated in humans. Our model suggests that chimpanzees cortical myelination was largely completed by the age of nine years, while iron accumulation continued throughout the lifespan. The regions with highest adult levels of myelin and iron took the longest to mature, challenging the widespread assumption that highly myelinated regions complete their development first. The reported maps and developmental curves provide a foundation for comparative neuroscience research and understanding of human brain evolution.

neuroscience↗

bioRxiv2023

Thalamic network controllability changes and cognitive impairment in multiple sclerosis

Recent research suggests that individuals with multiple sclerosis (MS) and cognitive impairment exhibit more effortful and less efficient transitions in brain network activity. Previous studies further highlight the increased vulnerability of specific regions, particularly the thalamus, to disease-related damage. This study investigates whether MS affects the controllability of specific brain regions in driving network activity transitions across the brain and examines the relationship between these changes and cognitive impairment in patients. Resting-state functional MRI and neuropsychological data were collected from 102 MS and 27 healthy controls. Functional network controllability analysis was performed to quantify how specific regions influence transitions between brain activity patterns or states. Disease alterations in controllability were assessed in the main dataset and then replicated in an independent dataset of 95 MS and 45 healthy controls. Controllability metrics were then used to distinguish MS from healthy controls and predict cognitive status. MS-specific controllability changes were observed in the subcortical network, particularly the thalamus, which were further confirmed in the replication dataset. Cognitively impaired patients showed significantly greater difficulty in the thalamus steering brain transitions towards difficult-to-reach states, which are typically associated with high-energy-cost cognitive functions. Thalamic network controllability proved more effective than thalamic volume in distinguishing MS from healthy controls (AUC = 88.3%), and in predicting cognitive status in MS (AUC = 80.7%). This study builds on previous research highlighting early thalamic damage in MS, aiming to demonstrate how this damage disrupts activity transitions across the cerebrum and may predict cognitive deficits. Our findings suggest that the thalamus in MS becomes less capable of facilitating broader brain activity transitions essential for high-energy-cost cognitive functions, implying a potential pathological mechanism that links thalamic functional changes to cognitive impairment in MS.

neuroscience↗

bioRxiv2023

Neuroinfectiology of an atypical anthrax-causing pathogen in wild chimpanzees

Bacillus cereus biovar anthracis (Bcbva) is an atypical anthrax-causing bacterium, inflicting wildlife fatalities across African rainforest ecosystems. The pathogens virulence in one of our closest living relatives, the chimpanzee, together with human serological evidence, suggests Bcbva is zoonotic. While classical B. anthracis-induced anthrax has been described to affect the central nervous system at a progressive disease-state, the neuroinfectiology of Bcbva is yet unknown. Here we characterised the pathogens neuro-invasiveness via gross pathological assessment, ultra-high resolution quantitative Magnetic Resonance Imaging and histological analysis on four brains, which were extracted from naturally deceased wild chimpanzees in Tai National Park, Cote dIvoire. Based on macroscopically evident pial vessel congestion and haemorrhages as well as cortical siderosis detected via MRI, we concluded that Bcbva induced meningitis analogous to B. anthracis. Further, histological visualisation of bacteria and leukocytes in the subarachnoid space evidenced the bacteriums capability to breach the arachnoid barrier. Bcbva was detected in the brain parenchyma of all four cases. This indicates a higher ability to transgress the glia limitans and therefore exhibits a higher neuroinvasiveness compared to B. anthracis that predominantly stays confined to the meninges. Heightened glial fibrillary acidic protein (GFAP) expression but little morphological gliosis suggest a rapid disease progression leading to host-death within hours to a few days after central nervous system invasion. Overall our results reveal Bcbvas ability to breach blood-brain barriers which results in a pronounced neuropathogenicity. Bcbva causes extensive damage to the meninges and the brain parenchyma, as well as rapid and massive digestion of brain extracellular matrix in chimpanzees and potentially so in humans in case of zoonotic spillover.

neuroscience↗

bioRxiv2022

B1+-correction of MT saturation maps optimized for 7T postmortem MRI of the brain

PurposeMagnetization transfer saturation (MTsat) is a useful marker to probe tissue macromolecular content and myelination in the brain. The increased [Formula] -inhomogeneity at [≥] 7T and significantly larger saturation pulse flip angles which are often used for postmortem studies exceed the limits where previous MTsat [Formula] correction methods are applicable. Here, we develop a calibration-based correction model and procedure, and validate and evaluate it in postmortem 7T data of whole chimpanzee brains. TheoryThe [Formula] dependence of MTsat was investigated by varying the off-resonance saturation pulse flip angle. For the range of saturation pulse flip angles applied in typical experiments on postmortem tissue, the dependence was close to linear. A linear model with a single calibration constant C is proposed to correct bias in MTsat by mapping it to the reference value of the saturation pulse flip angle. MethodsC was estimated voxel-wise in five postmortem chimpanzee brains. "Individual-based global parameters" were obtained by calculating the mean C within individual specimen brains and "group-based global parameters" by calculating the means of the individual-based global parameters across the five brains. ResultsThe linear calibration model described the data well, though C was not entirely independent of the underlying tissue and [Formula]. Individual-based and group-based global correction parameters (C = 1.2) led to visible, quantifiable reductions of [Formula]-biases in high resolution MTsat maps. ConclusionThe presented model and calibration approach effectively corrects for [Formula] in-homogeneities in postmortem 7T data.

neuroscience↗

bioRxiv2020

Can MRI measure myelin? Systematic review, qualitative assessment, and meta-analysis of studies validating microstructural imaging with myelin histology

Recent years have seen an increased understanding of the importance of myelination in healthy brain function and neuropsychiatric diseases. Non-invasive microstructural magnetic resonance imaging (MRI) holds the potential to expand and translate these insights to basic and clinical human research, but the sensitivity and specificity of different MR markers to myelination is a subject of debate. To consolidate current knowledge on the topic, we perform a systematic review and meta-analysis of studies that validate microstructural imaging by combining it with myelin histology. We find meta-analytic evidence for correlations between myelin histology and markers from different MRI modalities, including fractional anisotropy, radial diffusivity, macromolecular pool, magnetization transfer ratio, susceptibility and longitudinal relaxation rate, but not mean diffusivity. Meta-analytic correlation effect sizes range widely, between R2 = 0.26 and R2 = 0.82. However, formal comparisons between MRI-based myelin markers are limited by methodological variability, inconsistent reporting and potential for publication bias, thus preventing the establishment of a single most sensitive strategy to measure myelin with MRI. To facilitate further progress, we provide a detailed characterisation of the evaluated studies as an online resource. We also share a set of 12 recommendations for future studies validating putative MR-based myelin markers and deploying them in vivo in humans. HighlightsO_LISystematic review and meta-analysis of studies validating microstructural imaging with myelin histology C_LIO_LIWe find many MR markers are sensitive to myelin, including FA, RD, MP, MTR, Susceptibility, R1, but not MD C_LIO_LIFormal comparisons between MRI-based myelin markers are limited by methodological variability, inconsistent reporting and potential for publication bias C_LIO_LIResults emphasize the advantage of using multimodal imaging when testing hypotheses related to myelin in vivo in humans. C_LI

neuroscience↗

bioRxiv2019

Tractography in the presence of white matter lesions in multiple sclerosis

Accurate anatomical localisation of specific white matter tracts and the quantification of their tractspecific microstructural damage in multiple sclerosis (MS) can contribute to a better understanding of symptomatology, disease progression and intervention effects. Diffusion MRI-based tractography is being used increasingly to segment white matter tracts as regions-of-interest for subsequent quantitative analysis. Since MS lesions can interrupt the tractography algorithms tract reconstruction, clinical studies frequently resort to atlas-based approaches, which are convenient but ignorant to individual variability in tract size and shape. Here, we revisit the problem of individual tractography in MS, comparing tractography algorithms using: (i) The diffusion tensor framework; (ii) constrained spherical deconvoution (CSD); and (iii) damped Richardson-Lucy (dRL) deconvolution. Firstly, using simulated and in vivo data from 29 MS patients and 19 healthy controls, we show that the three tracking algorithms respond differentially to MS pathology. While the tensor-based approach is unable to deal with crossing fibres, CSD produces spurious stream-lines, in particular in tissue with high fibre loss and low diffusion anisotropy. With dRL, streamlines are increasingly interrupted in pathological tissue. Secondly, we demonstrate that despite the effects of lesion on the fibre orientation reconstruction algorithms, fibre tracking algorithms are still able to segment tracts that pass areas with high prevalence of lesions. Combining dRL-based tractography with an automated tract segmentation tool on data from 131 MS patients, the corticospinal tracts and arcuate fasciculi were successfully reconstructed in more than 90% of individuals. Comparing tractspecific microstructural parameters (fractional anisotropy, radial diffusivity and magnetisation transfer ratio) in individually segmented tracts to those from a tract probability map, we showed that there is no systematic disease-related bias in the individually reconstructed tracts, suggesting that lesions and otherwise damaged parts are not systematically omitted during tractography. Thirdly, we demonstrate modest anatomical correspondence between the individual and tract probability-based approach, with a spatial overlap between 35 and 55%. Correlations between tract-averaged microstructural parameters in individually segmented tracts and the probability-map approach ranged between r = .52 (p < .001) for radial diffusivity in the right cortico-spinal tract and r = .97 (p < .001) for magnetization transfer ratio in the arcuate fasciculi. Our results show that MS white matter lesions impact fibre orientation reconstructions but this does not appear to hinder the ability to anatomically localise white matter tracts in MS. Individual tract segmentation in MS is feasible on a large scale and could prove a powerful tool for investigating diagnostic and prognostic markers.

neuroscience↗