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Peters, J.

Publications and source records attributed to Peters, J..

At least 19 recordsLinked to original sources
bioRxiv2026

Item-specific clustering of high gamma-band activity on theta phase during speech categorization

Theta-gamma phase-amplitude coupling (PAC) has been proposed as a mechanism for separating neural representations in time. Although item-specific PAC has been reported, its role in perception remains unclear. Notably, previous work has shown that theta phase can bias perception, raising the question whether such biases are linked to phase-specific gamma activity. Here, we investigated whether phase-dependent perceptual biases are accompanied by item-specific theta-gamma PAC. We presented ambiguous speech sounds that could be interpreted as either /da/ or /ga/ in patients with epilepsy implanted with intracranial electrocorticography. We found that pre-stimulus theta phase predicted both the neural and perceptual response, with /da/ and /ga/ tuned channels exhibiting gamma activity clustering at distinct theta phases. These findings suggest that neural and perceptual biases stem from phase-specific pre-activation of item-specific neural representations. They demonstrate the generalizability of the theta-gamma code, shaping behavior and enhancing representational capacity.

neuroscience↗
bioRxiv2026

The representation of vocalizations in structured noise in the mouse auditory cortex

Efficient processing of complex acoustic signals within noisy environments is a fundamental challenge for the auditory system. This study investigates the cortical representation of structured noise and vocalizations embedded in it using widefield calcium imaging with the high-speed Calcium indicator jGCaMP8m in the mouse auditory cortex. The spectrotemporal statistics of the structured noise were controllable, including its temporal variance and cross-frequency correlations. We find that structured noise invokes spatially and temporally complex neural responses across the auditory cortex that reflect the spectrotemporal properties of the noise. We identified partially distinct noise response components: noise onset responses showed stronger overlap with primary than secondary areas, while later suppression components did not show a significant primary-secondary bias. Vocalization-evoked responses were significantly attenuated in the presence of noise compared to silent contexts, exhibiting reduced onset magnitude and altered adaptation dynamics. Using decoding we find the neural representation of vocalizations to become more discriminable with longer preceding noise exposure. Furthermore, structured noise cochleograms could be reconstructed from neural population activity, with performance depending on stimulus statistics, tending to be higher in primary than secondary auditory cortex while remaining substantial across both. These findings suggest that the mouse auditory cortex represents acoustic targets in noise through context-dependent and spatially distributed population activity, shaped by both the statistical structure and temporal history of the acoustic background.

neuroscience↗
bioRxiv2026

Polarized neutrons for the study of individual and collective fast dynamics in proteins

Neutron scattering is a powerful technique to investigate atomic structures and molecular dynamics of proteins at the nano-scale. When it comes to dynamics, incoherent and coherent scattering respectively provide information on the single and collective dynamics of nuclei. In proteins, hydrogen has the highest incoherent cross-section, and it is common practice to overlook the contribution of coherent terms stemming from all nuclei. However, the fast collective dynamics of heavier nuclei could also be studied if coherent scattering and incoherent scattering were experimentally separated. The recent advent of polarized neutron spectroscopy with sufficient flux and energy resolution has made it possible, and opens new perspectives to investigate the relative importance of coherent scattering and the information it provides on biological samples. The present study reports on the use of polarized quasi-elastic neutron scattering (QENS) and the application of a minimalistic model adapted to both individual and collective dynamics. Using a perdeuterated green fluorescent protein as a model globular protein, the study provides an interpretation of the dynamical parameters obtained with QENS, and a comparative study of the Elastic Coherent and Incoherent Scattering Factor. Based on both experiments and calculations, we discuss the relative importance of distinct and self components of coherent scattering, which is often wrongly assumed to be representative of collective dynamics only. The results highlight the current impediments rendering complicated a straightforward analysis of fast collective dynamics in hydrated protein samples.

biophysics↗
bioRxiv2026

nf_xpatial: A Reproducible Framework for Standardized Preprocessing and Clustering of Xenium Data

Recent advances in spatial transcriptomics have enabled the profiling of increasingly larger numbers of genes while retaining single-cell and subcellular resolution in situ. However, standardized bioinformatics workflows for analyzing these datasets have lagged behind, with existing pipelines focusing primarily on image processing and cell segmentation. To address this gap, we present nf_xpatial, a best-practices Nextflow pipeline for the downstream analysis of 10x Genomics Xenium data. The pipeline performs quality control, filtering, log and cell area normalization, multi-sample integration, and both expression-driven and spatially informed clustering across systematic parameter sweeps, allowing users to evaluate and compare clustering resolutions and spatial modeling parameters within a single reproducible run. Overall, nf_xpatial streamlines the processing of Xenium data from platform outputs to integrated single-cell and spatial clustering datasets, providing a standardized starting point from which biologists can fine-tune parameters and proceed to hypothesis-driven spatial analyses.

bioinformatics↗
bioRxiv2026

A conserved population of genetically defined striatal neurons gates opioid reward

A longstanding paradox in striatal circuit architecture is that opioid reward depends on -opioid receptors ({micro}ORs) in nucleus accumbens medium spiny neurons (MSNs), yet {micro}OR function is not explained by the canonical D1/direct and D2/indirect pathway organization. Here, we identify a rare MSN population marked by Chst9 that exhibits exceptionally high expression of the {micro}OR and is conserved across species. Notably, Chst9-MSNs comprise a specialized indirect pathway striatal neuron subtype that is molecularly and spatially distinct from canonical striatal populations. Opioids robustly silence Chst9-MSNs, and selective deletion of Oprm1 from this population abolishes fentanyl-conditioned place preference. These findings establish Chst9-MSNs as a critical substrate for opioid reward and define a new cellular framework for therapies targeting opioid use disorder.

neuroscience↗
bioRxiv2026

Hydration and H/D exchange-dependent infrared signatures of the GCN4 leucine zipper

Attenuated total reflectance Fourier-transform infrared (ATR-FTIR) spectroscopy of proteins in aqueous solution is often limited by water absorption and other optical artifacts. To overcome these limitations, we evaluated the structural features and hydrogen-deuterium exchange (HDX) kinetics of the -helical protein GCN4 in both hydrated (wet) and vacuum-dried (dry) states. While solvent heavily mask the second-derivative spectra of wet samples, vacuum drying yielded a thin, protein-rich film on the ATR crystal, significantly enhancing the signal-to-noise ratio and resolving the protein features without altering the native structure. Dry-state analysis clearly resolved the Amide I, Amide II, and deuterium-shifted Amide II (1450 cm-1) bands. Notably, second-derivative analysis of the dry spectra of the HDX samples revealed a bimodal Amide I distribution consisting of a stationary band at 1653 cm-1 from the solvent-inaccessible regions and an isotopically sensitive band shifting from 1648 cm-1 to 1644 cm-1 from solvent-accessible regions. These results demonstrate that vacuum-dried ATR-FTIR spectroscopy effectively eliminates solvent masking, providing the spectral clarity required to resolve discrete -helical sub-populations after deuteration.

biochemistry↗
bioRxiv2026

Urban green space exposure reduces subjective stress and physiological arousal

Stress is a major risk factor for mental disorders, and urban living is a key environmental contributor. Nature exposure may promote stress recovery and mental health, but how physiological arousal and subjective stress change across green versus gray space during naturalistic urban mobility is poorly understood. This preregistered study (https://doi.org/10.17605/OSF.IO/HF4RW) employed geolocation-based ambulatory assessment to examine psychophysiological arousal and subjective stress during transitions between urban green and gray environments. Thirty-six healthy urban residents completed a counterbalanced circular walking route in Cologne, Germany, with continuous GPS, cardiovascular, and electrodermal recording alongside ecological momentary assessment of subjective stress, affect, and exertion. Green compared to gray spaces were associated with lower subjective stress and higher affective well-being, with cardiac indices reflecting reduced autonomic arousal during green space exposure. Autonomic changes surrounding environmental transitions persisted beyond the immediate transition window, suggesting that physiological benefits of green space exposure extend into subsequent gray environments. These findings underscore the public health potential of urban green infrastructure for preventing stress-related mental health conditions.

physiology↗
bioRxiv2026

DNA supercoiling modulates bZIP transcription factor/DNA interaction

DNA topology is a key regulator of chromatin structure and transcription, yet its direct role in transcription factor recognition remains unclear. Here, we investigate how distinct DNA topological states modulate binding of the Saccharomyces cerevisiae bZIP transcription factor GCN4 using topologically defined plasmids. By combining, complementary biochemical approaches, including Bio-Layer Interferometry applied here for the first time to topology-dependent protein-DNA interactions, we show that DNA supercoiling directly reshapes GCN4-DNA recognition. Positively supercoiled DNA forms more stable and persistent complexes, whereas negatively supercoiled DNA retains greater conformational heterogeneity. To interpret these effects, we performed multiscale molecular simulations. Coarse-grained simulations of plasmids recapitulate the global topology-dependent trends observed experimentally, while matched minicircle models reproduce the same behaviour at the local scale. In strong agreement with experimental data, simulations reveal that DNA topology modulates the conformational ensemble of the GCN4 basic region. Overall, positively supercoiled DNA promotes a more ordered binding mode and localized protein distribution, whereas negatively supercoiled DNA supports increased structural plasticity. These findings identify DNA topology as an active determinant of transcription factor recognition and provide a multiscale framework linking global DNA mechanics to local protein-DNA interactions. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/722604v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@18f8ba9org.highwire.dtl.DTLVardef@11a395dorg.highwire.dtl.DTLVardef@ac093borg.highwire.dtl.DTLVardef@923212_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗
bioRxiv2026

DNA binding drives phase separation of the Gcn4 bZIP domain and reveals its conformational ensemble in the diluted and condensate phases

Liquid-liquid phase separation is widely invoked in transcriptional regulation, yet prevailing models attribute condensate formation primarily to intrinsically disordered activation domains rather than structured DNA-binding motifs. Here, we overturn this view by demonstrating that the isolated basic leucine zipper (bZIP) domain of the yeast transcription factor Gcn4 undergoes robust DNA-induced phase separation in the complete absence of its activation domain. Using small-angle X-ray scattering in combination with all-atom molecular dynamics simulations and ensemble optimization, we directly resolve the conformational landscape of the Gcn4 bZIP-DNA complex across coexisting dilute and condensed phases. Beyond the canonical uninterrupted helical conformation captured in crystal structures, we identify a previously unrecognized minor population featuring a pronounced helical kink at the basic region-leucine zipper junction. These findings establish DNA binding as a sufficient physical driver of bZIP phase separation and demonstrate that small-angle scattering can quantitatively interrogate protein conformational ensembles within biomolecular condensates, opening new avenues for the structural chemistry of phase-separated systems.

biophysics↗
bioRxiv2026

Individual Differences in Dopaminergic Modulation of Exploration-Exploitation Behaviour

Dopamine (DA) has been implicated in exploration-exploitation behaviour, i.e., exploring novel, potentially better options vs. exploiting known, previously rewarding options. Impairments in this trade-off occur in psychiatric disorders involving DAergic dysfunction, including addiction and schizophrenia. Pharmacological studies revealed a contribution of DA to exploration, but inconsistent findings suggest that interindividual variability in baseline DA may modulate effects. To address this, we investigated the effects of the DA precursor L-DOPA on exploration-exploitation during reinforcement learning in a sample of N = 75 healthy participants (n = 32 women), following a randomised, double-blind, placebo-controlled, pre-registered design (https://osf.io/p2r7u). We assessed whether putative baseline DA markers, including spontaneous eye blink rate, working memory (WM) capacity, and impulsivity, modulated drug effects and probed visual fixation patterns and pupil dilation as markers of exploration. L-DOPA had no overall effect on computational model parameters of random exploration, directed exploration or choice perseveration. WM capacity moderated drug effects on random exploration, with stronger effects at higher WM capacity. Remaining DA proxies showed no credible effects. Pooling the data from male participants with that from an earlier male-only study (Chakroun et al., 2020; total N = 74), L-DOPA increased uncertainty-dependent value weighting and perseveration strength, while decreasing habit updating, indicating a stronger tendency to repeat previous choices and slower decay of their influence over time. No credible drug effects were observed in female participants. Pupil dilation was tonically increased under L-DOPA and scaled with exploration behaviour and prediction error, confirming that pupillometry can index exploration-exploitation dynamics. Visual exploration patterns reflected uncertainty-driven sampling, but were unaffected by L-DOPA. Taken together, results suggest that DAergic modulation of exploration and perseveration behaviour may be contingent on cognitive capacity and sex, rather than exerting uniform effects across individuals.

neuroscience↗
bioRxiv2025

Image-Based Profiling of Induced Trophoblast Stem Cells Identifies Signatures Associated with Sex, Schizophrenia Genomic Risk and Placental Stress

Schizophrenia (SCZ) is a neurodevelopmental disorder where both genetic and environmental risks converge during pregnancy. Recent studies have highlighted the importance of placental biology in influencing risk of developing SCZ. However, the pathways by which genetic risk factors for SCZ interact with environmental influences to alter placental development are poorly understood. Through image-based profiling using Cell Painting, we leveraged trophoblast cultures derived from human induced pluripotent stem cells (hiPSCs) from male and female SCZ and neurotypical donors with varying placental genomic risk scores (PlacGRS) to explore the developmental dynamics of placental cells under normal growth and hypoxic stress. We employed both classical (e.g., CellProfiler) and deep learning feature extraction combined with downstream supervised machine learning to analyze high-dimensional data obtained from this hiPSC-derived model system, highlighting that these approaches overcome the inherent line-to-line variability in phenotypic analysis. Our findings reveal a salient nucleus-localized SCZ risk signature across cell lines, along with clear sexual dimorphism. This research underscores the capability of hiPSC-derived placenta models to elucidate complex interactions between genetic risk and environmental factors implicated in the neurodevelopment of SCZ, paving the way for future studies aimed at developing targeted therapeutic and prevention strategies.

neuroscience↗
bioRxiv2025

The Earlier You Know, the Smoother You Act

Intercepting a moving object with our hands requires that the moving object and the hand come into contact at some point along the objects trajectory. Hand movement must, therefore, be planned in advance so that the hand reaches a chosen spatial location along this trajectory at the correct moment in time. To enable such anticipatory behavior, the objects trajectory must be predicted based on sensory information collected before movement planning is concluded. Early completion of planning would allow for a smooth and economical movement; however, it also requires sufficiently accurate information about the objects movement to be available earlier. We investigate interception in the context of a complex, naturalistic motor task, toss juggling, to understand the extent to which proprioceptive and tactile information influence anticipatory movements of the catching hand. In our study, we compared solo juggling, where the efferent, tactile and proprioceptive information from the throwing hand is available during catch planning, with dyadic juggling, a functionally "deafferented" condition where no such information is available because the ball has been thrown by another person. Our results indicate that when internal and tactile information from the toss is absent, anticipatory behavior is greatly reduced. Experienced jugglers seem to rely more strongly on internal information than vision, allowing earlier planning and lower target uncertainty. In the dyadic condition, when internal information is absent, trajectory planning is delayed, leading to greater target uncertainty.

neuroscience↗
bioRxiv2025

Ghrelin and risky decision-making: No credible evidence for homeostatic state modulation of neural or behavioural effects

Risk-taking is often thought to depend on homeostatic systems. However, evidence remains mixed, and the underlying mechanisms remain debated. One candidate that might drive changes in risky decision-making due to changes in homeostatic systems may be the hunger hormone ghrelin, which interacts with the dopaminergic system. In two studies, we examined the effects of experimental interventions known to affect ghrelin levels on human risky choice in healthy male participants, either after a brief fasting period (study 1, N = 37; N = 26 for fMRI analyses) or a single night of total sleep deprivation (study 2, N = 40; N = 36 for fMRI analyses). We found no credible effects of the experimental manipulations on the proportion of risky choices. In addition, computational modelling indicated that the standard prospect theory, without accounting for choice repetition, best described the observed behaviour. However, it did not reveal consistent effects of state manipulations on model parameters, and the inclusion of manipulation-induced changes in ghrelin levels in the model likewise revealed no robust associations. FMRI analyses did not reveal effects of state manipulation on neural signatures of subjective value or choice in a priori defined regions of interest (bilateral ventromedial prefrontal cortex, ventral striatum, posterior cingulate cortex, and anterior cingulate cortex for subjective value; bilateral anterior insula, ventral striatum, and right medial prefrontal cortex for choice). Our results suggest that state-dependent influences on risky decision-making may be weaker than previously thought.

neuroscience↗
bioRxiv2025

Reduced Model-Based Control in Gambling Disorder Despite Intact Neural Value and Task Structure Representations

Disordered gambling has been linked to impairments in goal-directed (model-based) control and reinforcement learning. Here we investigated the potential neural basis of this impairment using a sequential reinforcement learning task (modified two-step-task), computational modeling, and functional magnetic resonance imaging (fMRI) in individuals exhibiting symptoms of disordered gambling (GD) and matched healthy controls (HC, n=30 per group). Model-agnostic analyses replicated the effects of reduced performance and reduced model-based control in the gambling group, both in terms of choice and response time effects. Computational modeling of choice behavior confirmed that this effect was due to reduced model-based control in the gambling group. Analyses of choices and response times using drift diffusion modeling revealed a more complex pattern, where behavioral impairments in the gambling group were linked to changes across several parameters reflecting drift rate modulation and asymptote, as well as non-decision time. Despite these pronounced behavioral differences, the gambling group exhibited largely intact neural effects related to the task transition structure, reward feedback and trial-to-trial behavioral adjustments. Results are discussed with respect to current neurocomputational models of behavioral dysregulation in disordered gambling.

neuroscience↗
bioRxiv2025

Catecholamine Precursor Modulation of Human Exploration:Evidence From a Large Gender-Balanced Sample

The catecholamine precursor tyrosine has been linked to improved cognitive performance, but investigations into decision-making and reinforcement learning processes known to be under catecholamine control are sparse. We examined the impact of a single dose of Tyrosine (2g) on reinforcement learning and exploration in a large (n=63) gender-balanced sample in a within-subjects preregistered study. Reinforcement learning performance was improved under Tyrosine, and computational modeling revealed that this performance increase was due to a stabilization of choice behavior reflected in increased value-driven exploitation. Further non-preregistered modeling analyses confirmed that accounting for higher-order perseveration substantially improved model fit, and substantiated the observation of increased value-driven exploitation under Tyrosine. Furthermore, it revealed a more fine-grained computational impact of Tyrosine, showing attenuated effects of directed exploration and value-independent perseveration. Supplementation with Tyrosine therefore improved reinforcement learning performance by stabilizing choice patterns in the service of optimizing reward accumulation. Results confirm that Tyrosine supplementation modulates specific computational mechanisms thought to be under catecholamine control.

neuroscience↗
bioRxiv2025

Human-specific morphoregulatory signatures in basal radial glia characterize neocortex evolution

As the seat of our cognition, the human neocortex is an object of immense fascination. Human neocortex expansion during evolution has been attributed to an increase in the proliferative capacity of neural progenitor cells during development, particularly basal radial glia (bRG). Despite their evolutionary relevance, the genomic changes driving human-specific bRG biology remain uncharacterized. We used comparative chromatin and transcriptional profiling of neural progenitor cells isolated from gorilla, chimpanzee and human cerebral organoids to identify cis-regulatory elements that have gained activity in humans. Focusing specifically on bRG, we discovered that morphoregulatory enhancer activity and gene expression signatures distinguish human bRG from other great apes. Functional analysis of the morphoregulatory genes FAM107A and CNGA3 in human organoids revealed that these genes are required for the morphological complexity of human bRG. Taken together, our interspecies comparison of basal radial glia suggests that human-specific morphoregulatory signatures characterize neocortex evolution.

neuroscience↗
bioRxiv2025

Recurrent Neural Network Exploration Strategies During Reinforcement Learning Depend on Network Capacity

Artificial neural networks constitute simplified computational models of neural circuits that might help understand how the biological brain solves and represents complex tasks. Previous research revealed that recurrent neural networks (RNNs) with 48 hidden units show human-level performance in restless four-armed bandit tasks but differ from humans with respect to the task strategy employed. Here we systematically examined the impact of network capacity (no. of hidden units) on computational mechanisms and performance. Computational modeling was applied to investigate and compare network behavior between capacity levels as well as between RNNs and human learners. Using a task frequently employed in human cognitive neuroscience work as well as in animal systems neuroscience work, we show that high-capacity networks displayed increased directed exploration and attenuated random exploration relative to low-capacity networks. RNNs with 576 hidden units approached "human-like" exploration strategies, but the overall switch rate and the level of perseveration still deviated from human learners. In the context of the resource-rational framework, which posits a trade-off between reward and policy complexity, human learners may devote more resources to solving the task, albeit without performance benefits over RNNs. Taken together, this work reveals the importance of network capacity on exploration strategies during reinforcement learning and therefore contributes to the goal of building neural networks that behave "human-like" to possibly gain insights into computational mechanisms in human brains.

animal behavior and cognition↗