Biology subjects

Müller, E.

Publications and source records attributed to Müller, E..

5 recordsLinked to original sources

bioRxiv2026

Spinal Recurrent Inhibition Shapes the Dynamics of TMS-induced Motor-Evoked Potentials: A Computational Modeling Study

Motor-evoked potentials (MEPs) recorded via surface electromyography (EMG) from peripheral muscles following transcranial magnetic stimulation (TMS) of the motor cortex reflect the integrity of the entire corticospinal pathway and are widely used in both basic neuroscience and clinical practice. However, the relative contributions of spinal and peripheral mechanisms to the observed MEP waveform remain poorly understood, partly because computational models that capture individual MEP characteristics are lacking. Here, we present a biologically plausible and computationally efficient model of the descending motor pathway, spanning the spinal cord and hand muscles, that can be fitted to individual MEP waveforms across a range of TMS intensities. The model successfully reproduces individual MEP waveforms, accounting for approximately 90% of the observed variance in waveforms across 10 healthy participants. Crucially, we demonstrate that recurrent inhibition of Renshaw cells in the spinal cord is indispensable for reproducing the fine temporal structure of MEP waveforms, even when input-output curve fitting appears adequate without it. Beyond waveform reproduction, the fitted model provides interpretable estimates of latent neural dynamics and subject-specific pathway parameters, including motor neuron size distribution, synaptic receptor balance, axonal conduction delay, and hand muscle refractoriness, that are consistent with known biological ranges. These results suggest that individual MEP waveforms, when analyzed using a biologically grounded model, carry substantially more information about spinal and peripheral motor pathway integrity than conventional amplitude-based measures alone.

neuroscience↗

bioRxiv2023

Criticality supports cross-frequency cortical-thalamic information transfer during conscious states

Consciousness is thought to be regulated by bidirectional information transfer between the cortex and thalamus, but the nature of this bidirectional communication - and its possible disruption in unconsciousness - remains poorly understood. Here, we present two main findings elucidating mechanisms of corticothalamic information transfer during conscious states. First, we identify a highly preserved spectral channel of cortical-thalamic communication which is present during conscious states but which is diminished during the loss of consciousness and enhanced during psychedelic states. Specifically, we show that in humans, mice, and rats, information sent from either the cortex or thalamus via{delta} /{theta}/ waves (~1.5-13 Hz) is consistently encoded by the other brain region by high{gamma} waves (~50-100 Hz); moroever, unconsciousness induced by propofol anesthesia or generalized spike-and-wave seizures diminishes this cross-frequency communication, whereas the psychedelic 5-methoxy-N,N/-dimethyltryptamine (5-MeO-DMT) enhances this interregional communication. Second, we leverage numerical simulations and neural electrophysiology recordings from the thalamus and cortex of human patients, rats, and mice to show that these changes in cross-frequency cortical-thalamic information transfer are mediated by excursions of low-frequency thalamocortical electrodynamics toward/away from edge-of-chaos criticality, or the phase transition from stability to chaos. Overall, our findings link thalamic-cortical communication to consciousness, and further offer a novel, mathematically well-defined framework to explain the disruption to thalamic-cortical information transfer during unconscious states.

neuroscience↗

bioRxiv2020

Diffuse neural coupling mediates complex network dynamics through the formation of quasi-critical brain states

The biological mechanisms that allow the brain to balance flexibility and integration remain poorly understood. A potential solution to this mystery may lie in a unique aspect of neurobiology, which is that numerous brain systems contain diffuse synaptic connectivity. In this manuscript, we demonstrate that increasing diffuse cortical coupling within a validated biophysical corticothalamic model traverses the system through a quasi-critical regime in which spatial heterogeneities in input noise support transient critical dynamics in distributed sub-regions. We then demonstrate that the presence of quasi-critical states coincides with known signatures of complex, adaptive brain network dynamics. Finally, we demonstrate the presence of similar dynamic signatures in empirical whole brain human neuroimaging data. Together, our results establish that modulating the balance between local and diffuse synaptic coupling in a thalamocortical model subtends the emergence of quasi-critical brain states that act to flexibly transition the brain between unique modes of information processing.

neuroscience↗

bioRxiv2020

Molecular investigations on a chimeric strain of Staphylococcus aureus sequence type 80

An Eritrean patient was admitted with suspected tuberculous cervical lymphadenitis. While no mycobacteria were detected in pus from this process, culture yielded PVL-positive, methicillin-susceptible Staphylococcus aureus. Microarray hybridisation assigned the isolate to clonal complex (CC) 80 but revealed unusual features, including the presence of the ORF-CM14 enterotoxin homologue and of an ACME-III element as well as the absence of etD and edinB. The isolate was subjected to both, Illumina and Nanopore sequencing allowing characterisation of deviating regions within the strains genome. Atypical features of this strain were attributable to the presence of two genomic regions that originated from other S. aureus lineages and that comprised, respectively, 3% and 1.4% of the genome. One deviating region extended from walJ to sirB. It comprised ORF-CM14 and the ACME-III element. A homologous, but larger fragment was also found in an atypical S. aureus CC1/ST567 strain whose lineage might have served as donor of this genomic region. This region itself is a chimera comprising fragments from CC1 as well as fragments of unknown origin. The other region of another 3% of the genome comprised the region from htsB to ecfA2. It was very similar to CC1 sequences. This suggests either an incorporation of CC1 DNA into the study strain, or it might alternatively suggest a recombination event affecting "canonical" CC80. As the study strain bears witness of several recombination events, such complex and large-scale events cannot be rare and exceptional, despite a mainly clonal nature of S. aureus. Although the exact mechanism is not yet clear, chimerism seems to be an additional pathway in the evolution of S. aureus, possibly being responsible for the transmission also of virulence and resistance factors. An organism that can shuffle, swap or exchange major parts of its genome by a yet unknown mechanism would have an evolutionary advantage compared to a strictly clonal organism.

microbiology↗

bioRxiv2019

Electron microscopy characterization of minerals formed in vitro by human bone cells and vascular smooth muscle cells

Soft tissue mineralization has been found to be a major component of diseases such as aortic valve stenosis and rheumatic heart disease. Cardiovascular mineralization has been suggested to follow mechanisms similar to those of bone formation with several cell culture models been developed over the years to provide mechanistic insights. These cell models have been characterized by a wide range of biochemical and molecular methods, which identified the presence of osteogenic markers and bone-like cells. However, there is a surprisingly small number of studies where the mineral formed in these cell culture models has been characterized by physico-chemical methods, and even fewer studies have compared this mineral to the one produced by bone cells in cultures. Here we investigated the morphology and composition of the minerals formed in cell cultures of vascular smooth muscle cells and bone cells. Electron microscopy and traditional cell mineralization assays were applied, revealing that vascular cells are indeed able to form calcified nodules of elemental composition similar to bone, however with different morphology. Comparison of morphologies of the two minerals to that found in cardiovascular tissue shows that some of tissue calcification resembles the calcified fibers produced by bone cells in vitro. These results suggest that the characterization of the mineral is of utmost importance and its morphology and chemical properties can contribute an important piece of information in the comprehensive analysis of soft tissue mineralization mechanisms, both in in vitro cell culture as well as in clinical samples.

pathology↗