Biology subjects

Hartmann, T.

Publications and source records attributed to Hartmann, T..

17 recordsLinked to original sources

bioRxiv2026

Brain-body timing gates conscious access across sensory systems

Conscious awareness fluctuates with the brains internal state at the moment of perception, yet how these states are temporally coordinated remains unclear. Although such internal states are reflected in ongoing neural activity, their temporal structure may arise from intrinsic interactions between the brain and the body. To test this hypothesis, we simultaneously recorded neural, cardiac, and respiratory activity while participants detected auditory, tactile, or visual stimuli presented at perceptual threshold. Across sensory modalities, stimulus detection was preceded by transient bursts of alpha-band (8-13 Hz) activity localized to lateralized prefrontal and premotor regions. Crucially, these neural events were aligned with specific phases of the cardiac and respiratory cycles, revealing coordinated brain-body states at the time of perception. This cross-system coupling predicted whether sensory stimuli reached conscious awareness. Together, these findings show that brain-body synchrony acts as a temporal gate for conscious access across sensory systems.

neuroscience↗

bioRxiv2025

Svirlpool: structural variant detection from long read sequencing by local assembly

MotivationLong-Read Sequencing (LRS), and Oxford Nanopore Technologies (ONT) in particular, has greatly improved the detection of structural genome variants (SVs). Fast alignment-based ONT callers achieve strong benchmark performance, but they necessarily reduce the read sequence to alignment-derived signals when deciding whether variants are shared across samples. This can be limiting for cohort and clinical analyses, especially for insertions and repeat regions where sequence representation matters. We present Svirlpool, a multi-sample SV caller for ONT data that builds local consensus assemblies of candidate SV regions and retains the assembled sequence up to the final joint-calling step, where merging tolerances are scaled by a reference-independent noise estimate derived from the reads. ResultsWe validated Svirlpool on two ONT family datasets: the recent high-quality HG002 Ashkenazi trio and the older Platinum Pedigree family, using the Genome in a Bottle and T2TQ100 benchmarks on the GRCh38, GRCh37, and CHM13v2 references and the Mendelian consistency of native multi-sample calls. We compare against current native joint callers and post-hoc merging workflows. Svirlpool produces highly Mendelian-consistent insertion calls in trio analyses (95.2% on GRCh38 and 95.1% on CHM13v2 at 30x), and on CHM13v2 it reaches the highest insertion and deletion consistency among all tested approaches. Sawfish and Sniffles achieve the highest SV benchmark F1 scores on recent high-quality ONT data, whereas Svirlpool enters the competition with more conservative SV calls. Svirlpool features native, sequence-aware joint calling with retained local consensus sequences and shows a very high Mendelian consistency with sequencing data from different batches and chemistries, which is a common situation in clinical application. Availability and Implementation: Source code, container images, and documentation available at https://github.com/bihealth/svirlpool. Contactvinzenz.may@bih-charite.de

bioinformatics↗

bioRxiv2025

Early Aβ-induced changes in the enteric nervous system and gut: structure, function, and motility

Alzheimers disease is increasingly recognized as affecting not only the central nervous system but also the autonomic nervous system, comprising the enteric nervous system, and thus the gut. Given the structural and functional similarities between the enteric and central nervous system, including susceptibility to A{beta}, this study investigated the early and acute effects of monomeric A{beta} on primary enteric neurons in vitro and on intestinal motility ex vivo. Acute A{beta} application caused marked neuronal hyperexcitability, with increased spike frequencies and calcium influx, and led to enhanced intestinal contractility without altering frequency or timing. Prolonged 72-hour exposure did not induce cell death or apoptosis but significantly reduced neurite outgrowth and decreased synaptic markers and beta II tubulin. These findings suggest that acute A{beta} primarily drives the excitability of enteric neurons and intestinal motility, while prolonged exposure subsequently leads to structural and synaptic changes. Overall, the study points to early dysfunction of the enteric nervous system in Alzheimers disease and highlights the gut as a potential target for early interventions. Synopsis O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/678722v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@18b5292org.highwire.dtl.DTLVardef@1da0ecforg.highwire.dtl.DTLVardef@1023b09org.highwire.dtl.DTLVardef@171e3fb_HPS_FORMAT_FIGEXP M_FIG C_FIG The pathology of Alzheimers disease is increasingly recognized in the enteric nervous system (ENS), suggesting an early contribution of the gut to the onset of the disease. This study investigated the acute and short-term effects of amyloid-{beta} (A{beta}) on intestinal motility and enteric neurons to elucidate early functional and structural changes beyond the brain. O_LIAcute A{beta} exposure enhanced intestinal contractility ex vivo. C_LIO_LIEnteric neurons showed hyperexcitability and increased Ca{superscript 2} influx. C_LIO_LIAfter 72 h, neuronal viability and apoptosis remained unaffected. C_LIO_LIProlonged exposure reduced neurite outgrowth and {beta}III-tubulin expression. C_LIO_LISynaptic density was significantly decreased. C_LI

neuroscience↗

bioRxiv2024

A novel in-vitro model of the bone marrow microenvironment in AML identifies CD44 and Focal Adhesion Kinase as therapeutic targets to reverse cell adhesion-mediated drug resistance

Acute myeloid leukemia (AML) is an aggressive neoplasm. Although most patients respond to induction therapy, they commonly relapse due to recurrent disease in the bone marrow microenvironment (BMME). So, disruption of the BMME, releasing tumour cells into the peripheral circulation, has therapeutic potential. Using both primary donor AML cells and cell lines, we developed an in-vitro co-culture model of the AML BMME. We used this model to identify the most effective agent(s) to block AML cell adherence and reverse adhesion-mediated treatment resistanc E. We identified anti-CD44 treatment significantly increased the efficacy of cytarabine. However, some AML cells remained adhered, and transcriptional analysis identified focal adhesion kinase (FAK) signalling as a contributing factor; adhered cells showed elevated FAK phosphorylation that was reduced by the FAK inhibitor, defactinib. Importantly, we demonstrated that anti-CD44 and defactinib were highly synergistic at diminishing adhesion of the most primitive CD34high AML cells in primary autologous co-cultures. Taken together, we identified anti-CD44 and defactinib as a promising therapeutic combination to release AML cells from the chemoprotective AML BMME. As anti-CD44 is already available as a recombinant humanised monoclonal antibody, the combination of this agent with defactinib could be rapidly tested in AML clinical trials.

cancer biology↗

bioRxiv2024

Mouse PAW: reverse-translating the FINGER multimodal lifestyle intervention enhances synaptic plasticity and cognition in adult wild type female mice

BackgroundTargeting multiple risk factors through preventive interventions can halt the onset or progression of dementia. The clinical efficacy of this approach was shown in the multimodal FINGER trial, yet knowledge of the underlying biological mechanisms is limited. In the current study, we applied for the first time a multimodal lifestyle intervention in mice to study effects on cognition and associated molecular pathways. MethodsWe have established a novel experimental model, the lifestyle intervention PAW (Prevention of Alzheimers by a Multimodal Lifestyle Protocol - Working-mechanisms for Memory Gains) in mice. In this model, we combined different modalities of intervention aiming to achieve synergistic effects. The animals were given access to running wheels (voluntary exercise), Fortasyn Connect (a medical food that slows disease progression in early Alzheimers disease), and they were subjected to cognitive training in an IntelliCage environment (PAW group). To separately investigate the effects of pharmacological vascular management as a preventive measure, another group of mice was given Atorvastatin and Enalapril (cholesterol and blood pressure lowering pharmaceuticals, respectively) dosed in the diet (Pharma group). Control mice were housed in normal conditions. We included 12 wild type C57BL/6J female mice 6.5 months of age per group. The full intervention lasted for 8 weeks. Blood pressure was measured at baseline and the end of the intervention. All mice underwent a battery of behavioural testing after the eight weeks of intervention. Hippocampi were dissected for proteomics analysis. ResultsDuring the intervention, the PAW group actively participated in the intervention by learning the different cognitive training programs and by using the running wheels. At the end of the intervention, the PAW group showed a lowering of blood pressure to a similar extent as in the Pharma group (systolic 158 mmHg to 139 mmHg, p = 0.003, and 163 mmHg to 136 mmHg, p = 0.042, respectively). Furthermore, the PAW group displayed a better short-term spatial working memory compared to the control group as assessed by the spontaneous alternation in the Y maze test (66.5% and 56.7%, respectively, p = 0.036). Proteomic analysis of the hippocampi and downstream bioinformatic analysis revealed that several pathways were upregulated in the PAW mice including synaptogenesis (Z = 4.27, p = 1.26E-18) and glutamate binding, activation of AMPA receptors and synaptic plasticity (Z = 3.74, p = 3.16E-19). ConclusionsOur findings suggest that the PAW model effectively mimics the clinical effects of multimodal lifestyle dementia prevention, and further demonstrates the activation of hippocampal-specific molecular drivers of memory gains.

neuroscience↗

bioRxiv2024

Carrier-frequency specific omission-related neural activity in ordered sound sequences are independent of omissions-predictability

Regularities in our surroundings lead to predictions about upcoming events. Previous research has shown, that omitted sounds during otherwise regular tone sequences elicit frequency-specific neural activity related to the upcoming but omitted tone. We tested whether this neural response is depending on the unpredictability of the omission. Therefore we recorded MEG data while participants listened to ordered or random tone sequences with omissions occurring either ordered or randomly. Using multivariate pattern analysis shows that the frequency-specific neural pattern during omission within ordered tone sequences occurs independent of the regularity of the omissions suggesting that the auditory predictions based on sensory experiences are not immediately updated by violations of those expectations.

neuroscience↗

bioRxiv2023

Modulation of Alzheimer's Disease Brain Pathology in Mice by Gut Bacterial Deletion: The Role of Il-17a and Microglial MyD88

Gut bacteria regulate brain pathology of Alzheimers disease (AD) patients and animal models; however, the underlying mechanism remains unclear. In this study, 3-month-old APP-transgenic female mice with and without knock-out of Il-17a gene, or haploinsufficiency of MyD88 in microglia were treated with antibiotics-supplemented or normal drinking water for 2 months. Antibiotic treatment eradicated gut bacteria, particularly in the phyla Bacteroidetes and Firmicutes, and reduced Il-17a-expressing CD4-positive T lymphocytes. Deletion of gut bacteria inhibited inflammatory activation in the brain and microglia, and reduced cerebral A{beta} levels in APP-transgenic mice, which was abolished by deficiency of Il-17a or haploinsufficiency of MyD88 in microglia. As possible mechanisms regulating A{beta} pathology, deletion of gut bacteria inhibited {beta}-secretase activity and increased the expression of Abcb1 and Lrp1 in the brain or at the blood-brain barrier, which were also reversed by the absence of Il-17a. Interestingly, a crossbreeding experiment between APP-transgenic mice and Il-17a knockout mice further showed that deficiency of Il-17a had already increased Abcb1 and Lrp1 expression at the blood-brain barrier. Thus, deletion of gut bacteria attenuates inflammatory activation and amyloid pathology in APP-transgenic mice via Il-17a and microglial MyD88-involved signalling pathways. Our study contributes to a better understanding of the gut-brain axis in AD pathophysiology.

neuroscience↗

bioRxiv2023

Prediction tendency, eye movements, and attention in a unified framework of neural speech tracking

Auditory speech comprehension is a multi-faceted process in which attention, prediction, and sensorimotor integration (via active sensing) interact with or complement each other. Although different conceptual models that focus on one of these aspects exist, we still lack a unified understanding of their role in speech processing. Here, we first replicated two recently published studies from our lab, confirming 1) a positive relationship between individual prediction tendencies and neural speech tracking, and 2) the phenomenon of ocular speech tracking - the tracking of attended speech by eye movements - and its shared contribution with neural activity to speech processing. In addition, we extended these findings with complementary analyses and investigated these phenomena in relation to each other in a multi-speaker paradigm with continuous, narrative speech. Importantly, prediction tendency and ocular speech tracking seem to be unrelated. In contrast to the shared contributions of oculomotor and neural activity to speech processing over a distributed set of brain regions that are critical for attention, individual prediction tendency and its relation to neural speech tracking seem to be largely independent of attention. Based on these findings, we propose a framework that aims to bridge the gaps between attention, prediction, and active (ocular) sensing in order to contribute to a holistic understanding of neural speech processing. In this speculative framework for listening, auditory inflow is, on a basic level, temporally modulated via active ocular sensing, and incoming information is interpreted based on probabilistic assumptions.

neuroscience↗

bioRxiv2023

Neural speech tracking benefit of lip movements predicts behavioral deterioration when the speaker's mouth is occluded

Observing lip movements of a speaker is known to facilitate speech understanding, especially in challenging listening situations. Converging evidence from neuroscientific studies shows enhanced processing of audiovisual stimuli. However, the interindividual variability of this visual benefit and its consequences on behavior are unknown. Here, we analyzed source-localized magnetoencephalographic (MEG) responses from normal-hearing participants listening to audiovisual speech with or without an additional distractor speaker. Using temporal response functions (TRFs), we show that neural responses to lip movements are, in general, enhanced when speech is challenging. After conducting a crucial control for speech acoustics, we show that lip movements effectively contribute to higher neural speech tracking, particularly when a distractor speaker is present. However, the extent of this visual benefit varied greatly among participants. Probing the behavioral relevance, we show that individuals who benefit more from lip movement information in terms of neural speech tracking, show a stronger drop in performance and an increase in perceived difficulty when the mouth is occluded by a surgical face mask. By contrast, no effect was found when the mouth was not occluded. We provide novel insights on how the benefit of lip movements in terms of neural speech tracking varies among individuals. Furthermore, we reveal its behavioral relevance by demonstrating negative consequences for behavior when visual speech is absent. Our results also offer potential implications for future objective assessments of audiovisual speech perception.

neuroscience↗

bioRxiv2023

Eye movements track prioritized auditory features in selective attention to natural speech

Over the last decades, cognitive neuroscience has identified a distributed set of brain regions that are critical for attention - one of the key principles of adaptive behavior. A strong anatomical overlap with brain regions critical for oculomotor processes suggests a joint network for attention and eye movements. However, the role of this shared network in complex, naturalistic environments remains understudied. Here, we investigated eye movements in relation to (un)attended sentences of natural speech in simultaneously recorded eye tracking and magnetoencephalographic (MEG) data. Using temporal response functions (TRF), we show that eye gaze tracks acoustic features (envelope and acoustic onsets) of attended speech, a phenomenon we termed ocular speech tracking. Ocular speech envelope tracking even differentiates a target from a distractor in a multi speaker context and is further related to intelligibility. Moreover, we provide evidence for its contribution to neural differences in speech processing, emphasizing the necessity to consider oculomotor activity in future research and in the interpretation of neural differences in auditory cognition. Our results extend previous findings of a joint network of attention and eye movement control as well as motor theories of speech. They provide valuable new directions for research into the neurobiological mechanisms of the phenomenon, its dependence on learning and plasticity, and its functional implications in social communication.

neuroscience↗

bioRxiv2021

Direct cochlear recordings show human hearing nerve activity is modulated by selective attention

The architecture of the efferent auditory system enables prioritization of strongly overlapping spatiotemporal cochlear activation patterns elicited by relevant and irrelevant inputs. So far, attempts at finding such attentional modulations of cochlear activity delivered indirect insights in humans or required direct recordings in animals. The extent to which spiral ganglion cells forming the human auditory nerve are sensitive to selective attention remains largely unknown. We investigated this question by testing the effects of attending to either the auditory or visual modality in human cochlear implant (CI) users (3 female, 13 male). Auditory nerve activity was directly recorded with standard CIs during a silent (anticipatory) cue-target interval. When attending the upcoming auditory input, ongoing auditory nerve activity within the theta range (5-8 Hz) was enhanced. Crucially, using the broadband signal (4-25 Hz), a classifier was even able to decode the attended modality from single-trial data. Follow-up analysis showed that the effect was not driven by a narrow frequency in particular. Using direct cochlear recordings from deaf individuals, our findings suggest that cochlear spiral ganglion cells are sensitive to top-down attentional modulations. Given the putatively broad hair-cell degeneration of these individuals, the effects are likely mediated by alternative efferent pathways as compared to previous studies using otoacoustic emissions. Successful classification of single-trial data could additionally have a significant impact on future closed-loop CI developments that incorporate real-time optimization of CI parameters based on the current mental state of the user. Significance StatementThe efferent auditory system in principle allows top-down modulation of auditory nerve activity, however evidence for this is lacking in humans. Using cochlear recordings in participants performing an audiovisual attention task, we show that ongoing auditory nerve activity in the silent cue-target period is directly modulated by selective attention. Specifically, ongoing auditory nerve activity is enhanced within the theta range when attending upcoming auditory input. Furthermore, over a broader frequency range, the attended modality can be decoded from single-trial data. Demonstrating this direct top-down influence on auditory nerve activity substantially extends previous works that focus on outer hair cell activity. Generally, our work could promote the use of standard cochlear implant electrodes to study cognitive neuroscientific questions.

neuroscience↗

bioRxiv2020

Increases in parieto-occipital alpha-band power reflect involuntary spatial attention due to a task-distracting deviant sound

Imagine you are focusing on the traffic on a busy street to ride your bike safely when suddenly you hear the siren of an ambulance. This unexpected sound involuntarily captures your attention and interferes with ongoing performance. We tested whether this type of distraction involves a spatial shift of attention. We measured behavioral data and magnetoencephalographic alpha power during a crossmodal paradigm that combined an exogenous cueing task and a distraction task. In each trial, a task-irrelevant sound preceded a visual target (left or right). The sound was usually the same animal sound (i.e., standard sound). Rarely, it was replaced by an unexpected environmental sound (i.e., deviant sound). Fifty percent of the deviants occurred on the same side as the target, and 50% occurred on the opposite side. Participants responded to the location of the target. As expected, responses were slower to targets that followed a deviant compared to a standard. Crucially, this distraction effect was mitigated by the spatial relationship between the targets and the deviants: responses were faster when targets followed deviants on the same versus different side, indexing a spatial shift of attention. This was further corroborated by a posterior alpha power modulation that was higher in the hemisphere ipsilateral (vs. contralateral) to the location of the attention-capturing deviant. We suggest that this alpha power lateralization reflects a spatial attention bias. Overall, our data support the contention that spatial shifts of attention contribute to deviant distraction.

neuroscience↗

bioRxiv2020

Economic Genome Assembly from Low Coverage Illumina and Nanopore Data

We describe a new approach to assemble genomes from a combination of low-coverage short and long reads. LazyBastard starts from a bipartite overlap graph between long reads and restrictively filtered short-read unitigs, which are then reduced to a long-read overlap graph G. Edges are removed from G to obtain first a consistent orientation and then a DAG. Using heuristics based on properties of proper interval graphs, contigs are extracted as maximum weight paths. These are translated into genomic sequence only in the final step. A prototype implementation of LazyBastard, entirely written in python, not only yields significantly more accurate assemblies of the yeast and fruit fly genomes compared to state-of-the-art pipelines but also requires much less computational effort. FundingRSF / Helmholtz Association 18-44-06201; Deutsche Academische Austauschdienst, DFG STA 850/19-2 within SPP 1738; German Federal Ministery of Education an Research 031A538A, de.NBI-RBC

bioinformatics↗

bioRxiv2019

Supramodal selective attention differentially adjusts frequency and phase of entrained oscillations in primary sensory areas and the dorsal attention network

Continuously prioritizing behaviourally relevant information from the environment for improved stimulus processing is a crucial function of attention. Low-frequency phase alignment of neural activity in primary sensory areas, with respect to attended/ignored features has been suggested to support top-down prioritization. Phase adjustment in frontoparietal regions has not been widely studied, despite general implication of these in top-down selection of information. In the current MEG study, we investigated how ongoing oscillatory activity of both sensory and non-sensory brain regions are differentially impacted by attentional focus. Participants performed an established intermodal selective attention task, where low-frequency auditory (1.6 Hz) and visual (1.8 Hz) stimuli were presented simultaneously. We instructed participants to either attend to the auditory or to the visual stimuli and to detect targets while ignoring the other stimulus stream. As expected, the strongest phase adjustment was observed in primary sensory regions for auditory and for visual stimulation, independent of attentional focus. We found greater differences in phase locking between attended and ignored stimulation for the visual modality. Interestingly, auditory temporal regions show small but significant attention-dependent entrainment even for visual stimulation. Extending findings from invasive recordings in non-human primates, we demonstrate an effect of attentional focus on the phase of the entrained oscillations in auditory and visual cortex which may be driven by phase locked increases of induced power. In contrast to the effects in sensory areas, attentional focus adjusted the peak frequencies in nonsensory areas. Spatially these areas show a striking overlap with core regions of the dorsal attention network and the frontoparietal network. This suggests that these areas prioritize the attended modality by optimally exploiting the temporal structure of stimulation. Overall, our study complements and extends previous work by showing a differential effect of attentional focus on entrained oscillations in primary sensory areas and frontoparietal areas.

neuroscience↗

bioRxiv2019

Auditory cortical generators of the Frequency Following Response are modulated by intermodal attention

The vast efferent connectivity of the auditory system suggests that subcortical (thalamic and brainstem) auditory regions should also be sensitive to top-down processes such as selective attention. In electrophysiology, the Frequency Following Response (FFR) to simple speech stimuli has been used extensively to study these subcortical areas. Despite being seemingly straight-forward in addressing the issue of attentional modulations of subcortical regions by means of the FFR, the existing results are highly inconsistent. Moreover, the notion that the FFR exclusively represents subcortical generators has been recently challenged. By applying these techniques to data recorded from 102 magnetoencephalography (MEG) magnetometers in 34 participants during a cross-modal attention task, we aimed to gain a more differentiated perspective on how the generators of the FFR are modulated by either attending to the visual or auditory input. In a first step our results confirm the strong contribution of also cortical regions to the FFR. Interestingly, of all regions exhibiting a measurable FFR response, only the right primary auditory cortex was significantly affected by intermodal attention. By showing a clear cortical contribution to the attentional FFR effect, our work significantly extends previous reports that focus on surface level recordings only. It underlines the importance of making a greater effort to disentangle the different contributing sources of the FFR and serves as a clear precaution of simplistically interpreting the FFR as brainstem response.

neuroscience↗

bioRxiv2019

Stereotactic electroencephalography in humans reveals multisensory signal in early visual and auditory cortices

Unequivocally demonstrating the presence of multisensory signals at the earliest stages of cortical processing remains challenging in humans. In our study, we relied on the unique spatio-temporal resolution provided by intracranial stereotactic electroencephalographic (SEEG) recordings in patients with drug-resistant epilepsy to characterize the signal extracted from early visual (calcarine and pericalcarine) and auditory (Heschls gyrus and planum temporale) regions during a simple audio-visual oddball task. We provide evidences that both cross-modal responses (visual responses in auditory cortex or the reverse) and multisensory processing (alteration of the unimodal responses during bimodal stimulation) can be observed in intracranial event-related potentials (iERPs) and in power modulations of oscillatory activity at different temporal scales within the first 150 ms after stimulus onset. The temporal profiles of the iERPs are compatible with the hypothesis that MSI occurs by means of direct pathways linking early visual and auditory regions. Our data indicate, moreover, that MSI mainly relies on modulations of the low-frequency bands (foremost the theta band in the auditory cortex and the alpha band in the visual cortex), suggesting the involvement of feedback pathways between the two sensory regions. Remarkably, we also observed high-gamma power modulations by sounds in the early visual cortex, thus suggesting the presence of neuronal populations involved in auditory processing in the calcarine and pericalcarine region in humans.

neuroscience↗

bioRxiv2018

CALISTA: Clustering And Lineage Inference in Single-Cell Transcriptional Analysis

We present CALISTA (Clustering and Lineage Inference in Single-Cell Transcriptional Analysis), a numerically efficient and highly scalable toolbox for an end-to-end analysis of single-cell transcriptomic profiles. CALISTA includes four essential single-cell analyses for cell differentiation studies, including single-cell clustering, reconstruction of cell lineage specification, transition gene identification, and pseudotemporal cell ordering. In these analyses, we employ a likelihood-based approach where single-cell mRNA counts are described by a probabilistic distribution function associated with stochastic gene transcriptional bursts and random technical dropout events. We evaluated the performance of CALISTA by analyzing single-cell gene expression datasets from in silico simulations and various single-cell transcriptional profiling technologies, comprising a few hundreds to tens of thousands of cells. A comparison with existing single-cell expression analyses, including MONOCLE 2 and SCANPY, demonstrated the superiority of CALISTA in reconstructing cell lineage progression and ordering cells along cell differentiation paths. CALISTA is freely available on https://www.cabselab.com/calista.

bioinformatics↗