Biology subjects

Schmidt, T. T.

Publications and source records attributed to Schmidt, T. T..

15 recordsLinked to original sources

bioRxiv2026

Escape from replicative crisis and immortalization precedes complex genome evolution

Shortening of telomeres restricts the proliferative capacity of human somatic cells by inducing replicative senescence and crisis. During cancerous transformation, premalignant cells must overcome these barriers and acquire replicative immortality. Single-cell DNA strand-specific genome sequencing of crisis cells revealed extreme genome instability characterized by complex chromosomal abnormalities. Unexpectedly, spontaneously emerging postcrisis clones showed relatively few and simple structural variants. However, with accumulating divisions following crisis escape, the genomes of immortal postcrisis clones evolve and amass genomic alterations, including tetraploidization events with subsequent losses and gains of individual chromosomes. Our data point towards a new model of tumorigenesis in which crisis acts as a strong selective barrier against cells with aberrant karyotypes, and in which high karyotypic complexity is acquired after immortalization and crisis escape.

cell biology↗

bioRxiv2026

Remembering touch: Somatosensory cortex supports long-term memory for dynamic vibrotactile patterns.

The neural substrates of tactile long-term memory (LTM) in humans remain poorly understood, as relatively few neuroimaging studies have addressed this question. Here, we asked whether retrieval of tactile stimulation engages modality-specific representations in the primary and secondary somatosensory cortices (S1 and S2), alongside domain-general retrieval networks. Participants learned 16 tactile trajectories, each presented for 1.2 s on the left thumb through sequential activation of 10 vibrating dots on a Braille-like display. Three learning sessions within one week were followed by a recognition test during functional magnetic resonance imaging (fMRI). In the final sample (n = 26), we contrasted BOLD responses during successful recognition of learned stimuli with those during correct rejection of novel stimuli. Successful recognition was associated with increased activity in contralateral S1 and S2, alongside activation in the hippocampus as well as frontal and parietal regions implicated in memory retrieval. A psychophysiological interaction analysis (PPI) further revealed increased task-dependent connectivity between the hippocampus and contralateral S1 and S2 during successful recognition. Together, these findings suggest that tactile long-term memory retrieval relies on coordinated hippocampal-somatosensory interactions and may engage long-term memory representations in somatosensory cortex.

neuroscience↗

bioRxiv2026

Time- and performance-dependent enhancement of tactospatial working memory caused by online anodal tDCS of the posterior parietal cortex

BackgroundSpatial working memory (WM) relies on posterior parietal cortex (PPC) within a distributed fronto-parietal network, yet whether online anodal transcranial direct current stimulation (tDCS) of PPC modulates tactile WM, and how behavioral effects unfold over time, remains unclear. ObjectiveWe tested whether online anodal tDCS over left PPC modulates performance in a tactospatial WM task and whether stimulation effects vary over time and as a function of baseline performance. MethodsIn a double-blind, sham-controlled, within-subject crossover design, 32 healthy adults completed two counterbalanced sessions (Active, Sham). Each session comprised baseline, stimulation, and post-stimulation phases while participants performed a retro-cued delayed match-to-sample task with vibrotactile patterns delivered to the left index finger. During the stimulation phase, participants received either 2 mA anodal or sham tDCS over left PPC for 15 min, depending on session. Behavioral accuracy was analyzed using a sliding-window approach combined with cluster-based permutation testing. ResultsActive stimulation induced a significant, gradual improvement in WM accuracy relative to sham, emerging approximately eight minutes after stimulation onset and corresponding to a [~]5% performance increase (Hedges g = 0.43). Stimulation effects were baseline-dependent, with individuals showing lower initial WM performance exhibiting larger behavioral gains, whereas high performers showed minimal benefits. ConclusionsThese findings show that online anodal stimulation of left PPC can modulate tactile WM performance in a time- and baseline-dependent manner. More broadly, the results suggest that behavioral effects of parietal tDCS emerge gradually during ongoing stimulation and depend on initial cognitive state. HighlightsO_LIOnline anodal PPC-tDCS enhances tactile working memory C_LIO_LIBehavioral gains emerge after [~]8 min of stimulation C_LIO_LIActive stimulation improves accuracy by [~]5% versus sham C_LIO_LILower baseline performers show larger stimulation benefits C_LIO_LISliding-window analyses capture dynamic online tDCS effects C_LI

neuroscience↗

bioRxiv2026

Decoding Graded Grip-Force Intensity from fMRI Data Reveals a Transformation from Abstract to Effector- and Movement-Specific Codes prior to Execution

Motor planning entails a progressive transformation of neural representations--from abstract motor goals, which represent intended action-outcomes independent of any particular effector (i.e., the body part executing the action), to effector-specific movement plans. Functional MRI (fMRI) studies have shown that parametric variations in parietal activity patterns reflect the encoding of intended force intensities in effector-specific regions, even before detailed movement parameters are specified. However, how these intended force intensities are initially represented in an abstract, effector-independent format and subsequently transformed into effector- and movement-specific plans remains unclear. To address this, human participants performed a delayed grip-force task during fMRI. They first prepared two of four possible force intensities, then received a cue indicating which hand should apply which force, and finally executed both grips simultaneously. Using time-resolved support vector regression (SVR) combined with a searchlight approach, we identified brain regions that parametrically code grip-force intensities across two 6-second delay periods. During the first delay, above-chance decoding was observed in the precuneus (PCu), whereas during the second delay it emerged in effector-specific regions, including the contralateral intraparietal sulcus (pIPS/aIPS), primary somatosensory cortex (S1), dorsal premotor cortex (PMd), and supplementary motor area (SMA). Cross-decoding confirmed effector-independent coding in the PCu, while cross-temporal generalization revealed stable representations in the contralateral IPS and PMd from the second delay through execution. Together, these findings indicate a progressive transformation from abstract representations of intended force intensity in the PCu to effector- and movement-specific plans in the IPS and PMd.

neuroscience↗

bioRxiv2025

Nanopore-based profiling of PEGylation in nucleic acid therapeutics

Nucleic acid therapeutics, including aptamers, offer effective strategies for programmable and targeted disease treatment. To improve their stability and circulation time, oligonucleotides are often conjugated to hydrophilic polymers such as polyethylene glycol (PEG). However, current bulk techniques fail to resolve PEG heterogeneity, especially in complex biological environments. Here, we use nanopore sensing to quantify PEG conjugation efficiency of the FDA-approved RNA aptamer pegaptanib. We assembled DNA nanostructures that bind pegaptanib and then we used solid-state nanopores to quantify pegaptanib PEGylation. We further assess pegaptanib PEGylation and stability in a serum background and demonstrate that nanopore sensing resolves PEG moieties of distinct molecular weights within oligonucleotide conjugates. Single-molecule profiling of polymer-RNA conjugates enables iterative improvements in oligonucleotide design and provides a direct means to assess their stability in complex biological environments, thereby advancing the development of more effective nucleic acid therapeutics.

bioengineering↗

bioRxiv2024

Decoding Parametric Grip-Force Anticipation from fMRI-Data

Previous functional magnetic resonance imaging (fMRI) studies have shown that activity in premotor and parietal brain-regions covaries with the intensity of upcoming grip-force. However, it remains unclear how information about the intended grip-force intensity is initially represented and subsequently transformed into a motor code before motor-execution. In this fMRI study, we used multivoxel pattern analysis (MVPA) to decode where and when information about grip-force intensities is parametrically coded in the brain. Human participants performed a delayed grip-force task in which one of four cued levels of grip-force intensity had to be maintained in working memory (WM) during a 9-second delay-period preceding motor execution. Using time-resolved MVPA, with a searchlight approach and support vector regression (SVR), we tested which brain regions exhibit multivariate WM codes of anticipated grip-force intensities. During an early delay-period, we observed above-chance decoding in the ventromedial prefrontal cortex (vmPFC). During a late delay-period, we found a network of action-specific brain regions, including the bilateral intraparietal sulcus (IPS), left dorsal premotor cortex (l-PMd) and supplementary motor areas (SMA). Additionally, cross-regression decoding was employed to test for temporal generalization of activation patterns between early and late delay-periods with those during cue presentation and motor execution. Cross-regression decoding indicated temporal generalization to the cue-period in the vmPFC, and to motor-execution in the l-IPS and l-PMd. Together, these findings suggest that the WM representation of grip-force intensities undergoes a transformation where the vmPFC encodes information about the intended grip-force, which is subsequently converted into a motor code in the l-IPS and l-PMd before execution.

neuroscience↗

bioRxiv2024

Effector-Specific Neural Representations of Perceptual Decisions Independent of Motor Actions and Sensory Modalities

Neuroscientific research has shown that perceptual decision-making occurs in effector-specific brain regions that are associated with the required motor response. Recent functional magnetic resonance imaging (fMRI) studies that dissociated decisions from coinciding processes, such as motor actions partly challenge this, indicating abstract representations that might vary across stimulus modalities. However, cross-modal comparisons have been difficult since most task designs differ not only in modality but also in effectors, motor response, and level of abstraction. Here, we describe an fMRI experiment where participants compared frequencies of two sequentially presented visual flicker stimuli in a delayed match-to-comparison task, which controlled for motor actions and stimulus sequence. Using Bayesian modelling, we estimated subjective frequency differences based on the time order effect. These values were applied in support vector regression analysis of a multi-voxel pattern whole-brain searchlight approach to identify brain regions containing information on subjective decision values. Furthermore, a conjunction analysis with data from a re-analyzed analogue vibrotactile study was conducted for a cross-modal comparison. Both analyses revealed significant activation patterns in the left dorsal (PMd) and ventral (PMv) premotor cortex as well as in the bilateral intraparietal sulcus (IPS). While previous primate and human imaging research have implicated these regions in transforming sensory information into action, our findings indicate that the IPS processes abstract decision signals while PMd and PMv represent an effector-specific, but motor response independent encoding of perceptual decisions that persists across sensory domains.

neuroscience↗

bioRxiv2024

Thalamocortical interactions reflecting the intensity of flicker light-induced visual hallucinatory phenomena

The thalamus has a critical role in the orchestration of cortical activity. Aberrant thalamocortical connectivity occurs together with visual hallucinations in various pathologies and drug-induced states, highlighting the need to better understand how thalamocortical interactions may contribute to hallucinatory phenomena. However, concurring symptoms and physiological changes that occur during psychopathologies and pharmacological interventions make it difficult to distil the specific neural correlates of hallucinatory experiences. Flicker light stimulation (FLS) at 10 Hz reliably and selectively induces transient visual hallucinations in healthy participants. Arrhythmic flicker elicits fewer hallucinatory effects while delivering equal amounts of visual stimulation, together facilitating a well-controlled experimental setup to investigate the neural correlates of visual hallucinations driven by flicker rhythmicity. In this study, we implemented rhythmic and arrhythmic FLS during fMRI scanning to test the elicited changes in cortical activation and thalamocortical functional connectivity. We found that rhythmic FLS elicited stronger activation in higher-order visual cortices compared to arrhythmic control. Consistently, we found that rhythmic flicker selectively increased connectivity between ventroanterior thalamic nuclei and higher-order visual cortices compared to arrhythmic control, which was also found be positively associated with the subjective intensity of visual hallucinatory effects. As these thalamic and cortical areas do not receive primary visual inputs, it suggests that the thalamocortical connectivity changes relate to a higher-order function of the thalamus, such as in the coordination of cortical activity. In sum, we present novel evidence for the role of specific thalamocortical interactions with ventroanterior nuclei within visual hallucinatory experiences. Importantly, this can inform future clinical research into the mechanistic underpinnings of pathologic hallucinations.

neuroscience↗

bioRxiv2023

High resolution long-read telomere sequencing reveals dynamic mechanisms in aging and cancer

Telomeres are the protective nucleoprotein structures at the end of linear eukaryotic chromosomes. Telomeres repetitive nature and length have traditionally challenged the precise assessment of the composition and length of individual human telomeres. Here, we present Telo-seq to resolve bulk, chromosome arm-specific and allele-specific human telomere lengths using Oxford Nanopore Technologies native long-read sequencing. Telo-seq resolves telomere shortening in five population doubling increments and reveals intrasample, chromosome arm-specific, allele-specific telomere length heterogeneity. Telo-seq can reliably discriminate between telomerase- and ALT-positive cancer cell lines. Thus, Telo-seq is a novel tool to study telomere biology during development, aging, and cancer at unprecedented resolution.

cell biology↗

bioRxiv2023

Flicker light stimulation induces thalamocortical hyperconnectivity with LGN and higher-order thalamic nuclei

The thalamus is primarily known as a relay for sensory information; however, it also critically contributes to higher-order cortical processing and coordination. Thalamocortical hyperconnectivity is associated with hallucinatory phenomena that occur in various psychopathologies (e.g., psychosis, migraine aura) and altered states of consciousness (ASC, e.g., induced by psychedelic drugs). However, the exact functional contribution of thalamocortical hyperconnectivity in forming hallucinatory experiences is unclear. Flicker light stimulation (FLS) can be used as an experimental tool to induce transient visual hallucinatory phenomena in healthy participants. Here, we use FLS in combination with fMRI to test how FLS modulates thalamocortical connectivity between specific thalamic nuclei and visual areas. We show that FLS induces thalamocortical hyperconnectivity between LGN, early visual areas and proximal upstream areas of ventral and dorsal visual streams (e.g., hV4, VO1, V3a). Further, an exploratory analysis indicates specific higher-order thalamic nuclei, such as anterior and mediodorsal nuclei, to be strongly affected by FLS. Here, the connectivity changes to upstream cortical visual areas directly reflect a frequency-dependent increase in experienced visual phenomena. Together these findings contribute to the identification of specific thalamocortical interactions in the emergence of visual hallucinations. HighlightsO_LIFlicker light stimulation (FLS) induces thalamocortical hyperconnectivity between the first-order thalamic LGN and early visual cortices, likely due to entrainment. C_LIO_LIThalamocortical connectivity between LGN and upstream visual areas, but not V1, is associated with the intensity of visual hallucinations. C_LIO_LIThalamocortical connectivity changes with higher-order thalamic nuclei, such as anterior and mediodorsal nuclei, show strongest modulation by flicker frequency, which corresponds to the intensity of visual hallucinations. C_LI

neuroscience↗

bioRxiv2022

Dose-response relationships of LSD-induced subjective experiences in humans

Lysergic acid diethylamide (LSD) is a potent classic serotonergic psychedelic, which facilitates a variety of altered states of consciousness. Here we present the first meta-analysis establishing dose-response relationship estimates of the altered experience induced by LSD. Data extracted from articles identified by a systematic literature review following PRISMA guidelines were obtained from the Altered States Database. The psychometric data comprised ratings of subjective effects from standardized and validated questionnaires: the Altered States of Consciousness Rating Scale (5D-ASC, 11-ASC) and the Mystical Experience Questionnaire (MEQ30). We performed meta-regression analyses using restricted cubic splines for data from studies with LSD doses of up to 200 g base. Most scales revealed a sigmoid-like increase of effects with a plateauing at around 100 g. The most strongly modulated factors referred to changes in perception and illusory imagination, followed by positively experienced ego-dissolution, while only small effects were found for Anxiety and Dread of Ego Dissolution. The partly observed considerable variability of effects points to the importance of non-pharmacological effects on subjective experiences. The established dose-response relationships may be used as general references for future experimental and clinical research on LSD to relate observed with expected subjective effects and to elucidate phenomenological differences between psychedelics.

neuroscience↗

bioRxiv2021

Differences in working memory coding of biological motion attributed to oneself and others

The question how the brain distinguishes between information about oneself and the rest of the world is of fundamental interest to both philosophy and neuroscience. This question can be approached empirically by investigating how associating stimuli with oneself leads to differences in neurocognitive processing. However, little is known about the brain network involved in forming such self-associations for, specifically, bodily stimuli. In this fMRI study, we sought to distinguish the neural substrates of representing a full-body movement as ones movement and as someone elses movement. Participants performed a delayed match-to-sample working memory task where a retained full-body movement (displayed using point-light walkers) was arbitrarily labelled as ones own movement or as performed by someone else. By using arbitrary associations we aimed to address a limitation of previous studies, namely that our own movements are more familiar to us than movements of other people. A searchlight multivariate decoding analysis was used to test where information about types of movement and about self-association was coded. Movement specific activation patterns was found in a network of regions also involved in perceptual processing of movement stimuli, however not in early sensory regions. Information about whether a memorized movement was associated with the self or with another person was found to be coded by activity in the left middle frontal gyrus (MFG), left inferior frontal gyrus (IFG), bilateral supplementary motor area, and (at reduced threshold) in the left temporoparietal junction (TPJ). These areas are frequently reported as involved in action understanding (IFG, MFG) and domain-general self/other distinction (TPJ). Finally, in univariate analysis we found that selecting a self-associated movement for retention was related to increased activity in the ventral medial prefrontal cortex.

neuroscience↗

bioRxiv2021

Enhanced processing of aversive stimuli on embodied artificial limbs by the human amygdala

Body perception has been extensively investigated, with one particular focus being the integration of vision and touch within a neuronal body representation. Previous studies have implicated a distributed network comprising the extrastriate body area (EBA), posterior parietal cortex (PPC) and ventral premotor cortex (PMv) during illusory self-attribution of a rubber hand. Here, we set up an fMRI paradigm in virtual reality (VR) to study whether and how threatening (artificial) body parts affects their self-attribution. Participants (N=30) saw a spider (aversive stimulus) or a toy-car (neutral stimulus) moving along a 3D-rendered virtual forearm positioned like their real forearm, while tactile stimulation was applied on the real arm in the same (congruent) or opposite (incongruent) direction. We found that the PPC was more activated during congruent stimulation; higher visual areas and the anterior insula (aIns) showed increased activation during aversive stimulus presentation; and the amygdala was more strongly activated for aversive stimuli when there was stronger multisensory integration of body-related information (interaction of aversiveness and congruency). Together, these findings suggest an enhanced processing of aversive stimuli within the amygdala when they represent a bodily threat.

neuroscience↗

bioRxiv2020

Is Kambo psychoactive? Acute and subacute effects of the secretion of the Giant Maki Frog (Phyllomedusa bicolor) on human consciousness.

Kambo is the name for the secretion of the Giant Leaf Frog (Phyllomedusa bicolor) containing a plethora of bioactive peptides. Originally, it is ritually used by different ethnicities from the Amazon basin as a remedy against bad luck in hunting. In the last twenty years, Kambo has spread to Western urban centers, often associated with the use of ayahuasca. Anecdotal reports claim beneficial effects on wellbeing and different medical and mental health conditions. However, to date it has been controversial if Kambo elicits altered states of consciousness. Here we retrospectively investigated acute and subacute psychological effects of Kambo in a sample of n = 22 anonymous users (n = 22, mean age: 39 years, {+/-} 8.5; 45.5% female), administering standardized questionnaires for the assessment of psychoactive effects. Acutely, participants reported psychological effects which remained on a mild to moderate level, but no psychedelic-type distortions of perception or thinking. In contrast, persisting effects were predominantly described as positive and pleasant, revealing surprisingly high measures of personal and spiritual significance. Subacute and long-term effects showed some overlap with the "afterglow" phenomena that follow the use of serotonergic psychedelics.

pharmacology and toxicology↗

bioRxiv2020

How does it feel to be on psilocybin? Dose-response relationships of subjective experiences in humans.

Psilocybin is the active component of magic mushrooms and is well known for its psychoactive properties. Different questionnaires have been developed to systematically quantify altered states of consciousness induced by psychoactive drugs. The aim of this study was to obtain the dose-response relationships of the subjective experiences induced by psilocybin in healthy study participants. For this purpose, we applied a linear meta-regression approach on questionnaire ratings after oral administration of psilocybin in a controlled setting. Data was obtained from The Altered States Database, which contains psychometric data extracted from peer-reviewed articles published in MEDLINE-listed journals that used standardized and validated questionnaires. Our meta-analysis included data of the Altered States of Consciousness Rating Scale, the Mystical Experience Questionnaire (MEQ30), and the Hallucinogen Rating Scale (HRS). We used the Robust Variance Estimation Framework to obtain linear dose-response relationship estimates for each dimension of the given questionnaires. Ratings on most dimensions and subscales of the included questionnaires correlated positively with dose. Since subjective experiences are not only determined by dose, but also by individual differences and environmental factors, our results do not necessarily generalize to recreational use, as our analyses are based on data from controlled laboratory experiments. The paper at hand could serve as a general literature citation for the use of psilocybin in experimental and clinical research, especially for the comparison of expected and observed subjective drug experiences.

neuroscience↗