Biology subjects

Bayram, B.

Publications and source records attributed to Bayram, B..

5 recordsLinked to original sources

bioRxiv2025

Peripheral Complement C4 Protein in Schizophrenia: Association with Gene Copy Number and Immune Cell Subtypes

The lack of disease-modifying treatments for schizophrenia necessitates the exploration of novel aspects of its pathophysiology, including innate immune mechanisms in the periphery. C4 protein activation, associated with the complement cascade of innate immunity, associates with symptoms and predicts outcomes. However, C4 protein activation does not coincide with expected changes to other proteins in the complement cascade, suggesting another source of C4 protein activation. Using a combination of fresh whole blood from ten anonymous donors and a large set of publicly available microarray data, we show, for the first time, that C4 protein is found and expressed primarily in neutrophils and monocytes. Then, we compared the correlation between C4 protein in neutrophils, classical monocytes, plasma and the number of C4A gene copies. We determined the number of C4A genes using digital droplet PCR, C4 protein in neutrophils (15 patients/21 controls) and plasma (30 patients/38 controls) using western blotting, and classical monocytes (30 patients/38 controls) using flow cytometry. We found a moderate positive correlation between the number of C4A gene copies and the amount of C4 protein only in neutrophils and only in the schizophrenia group (Spearmans rho, r = 0.64, p = 0.01, Cohens d [~]1.67). Our results indicate a convergence of innate immunity mechanisms associated with schizophrenia. This novel mechanism of innate immunity in schizophrenia deserves further study to determine whether it could be a useful drug target.

immunology↗

bioRxiv2025

Arousal-related mediation of perceptual belief updating across auditory domains

Belief updating refers to the integration of prior beliefs with incoming evidence and guides decision-making under uncertainty. In response to surprising events, this process is thought to be modulated by the locus-coeruleus-noradrenaline (LC-NA) arousal system, observable via pupil dilations (PDs). Pertinent literature has mostly focused on conscious, high-level decision-making and estimation processes, while assuming that the same principles apply to low-level sensory perceptual decision-making and generalize across tasks, domains and modalities. To address some of these assumptions, we devised a novel perceptual discrimination paradigm, investigating behavior and PDs across auditory domains. Participants were presented with auditory sequences of randomized length at a rapid pace, changing intermittently between two latent states: acceleration vs. deceleration (temporal group, N = 25) and clockwise vs. counterclockwise movement (spatial group, N = 22). Under high uncertainty, participants continuously inferred latent states to report the final state per sequence. To extract per-stimulus estimates of PDs during sequences, we fitted a deconvolution-based general linear model to the continuous pupil traces with a free amplitude parameter reflecting ongoing PDs. A Bayesian observer model was fitted to participants responses and used to estimate information gain and surprisal for every stimulus. Participants performance and PDs showed strong sensitivity to the occurrence of change-points. Both computational variables significantly predicted PDs in both domains, with information gain outperforming surprisal in a model comparison. Further model comparison revealed significant preference for models excluding possible domain-specific effects over models including them, pointing towards a constant effect over domains. We conclude that behavior and associated PDs observed in our purely perceptual auditory task align with Bayesian principles of belief updating. The observed lack of domain specificity supports the assumed generalizability of belief updating.

neuroscience↗

bioRxiv2025

Breathing strategies to influence perception: Evidence for interoceptive and exteroceptive active sensing

Recent research indicates that humans continuously and automatically modulate their breathing to temporally align exteroceptive stimuli with specific phases of the respiratory cycle. This process has been interpreted as a form of active sensing and is associated with faster responses and improved perceptual accuracy. While converging evidence suggests that respiration also shapes interoceptive processing at both neural and behavioural levels, it remains unclear whether individuals actively adjust their breathing to optimize interoceptive performance. In this study, we examined whether healthy participants modulated their respiration during an interoceptive (heartbeat discrimination) and an exteroceptive (tactile detection) task. We analysed respiration both in terms of time-locked activity and inter-trial phase coherence relative to stimulus onset and assessed their relationship with perceptual accuracy. Our results demonstrated that participants systematically adjust their breathing in both amplitude and phase, synchronizing respiration to the anticipated (i.e., cued) onset of stimuli in both tasks. Crucially, task performance was enhanced during exhalation compared to inhalation, suggesting that respiratory modulation supports the perception of both interoceptive and exteroceptive signals. Significance statementThis study reveals that humans not only synchronize their breathing to anticipated external and internal stimuli, but also perform better when perceiving them during exhalation. By showing that respiration is modulated in both interoceptive and exteroceptive contexts, our findings extend the concept of active sensing to internal bodily awareness. This has important implications for understanding the dynamic interplay between physiology and perception and may guide interventions aimed at improving clinical outcomes in conditions where interoception is disrupted.

neuroscience↗

bioRxiv2025

Cardio-respiratory interactions in interoceptive perception: The role of heartbeat-modulated cortical oscillations

The cardiovascular and respiratory systems are anatomically and functionally integrated within the cardio-respiratory system. This close connection suggests that breathing continuously shapes cardiac interoceptive perception. Previously, we demonstrated cardio-respiratory interoceptive interactions in the heartbeat-evoked potential, a neural marker of cortical processing of cardiac signals. Specifically, we observed enhanced late heartbeat-evoked potential positivity and greater interoceptive accuracy during exhalation compared to inhalation in participants engaged in cardiac interoceptive tasks. Here, we extended these findings to the time-frequency domain by reanalysing our previous dataset. We investigated heartbeat-modulated cortical oscillations, examining power, inter-trial coherence, and functional connectivity across the respiratory cycle at rest, during a cardiac interoceptive task (heartbeat counting), and an exteroceptive control task (cardiac-tone counting). Results revealed that during the heartbeat counting task, late heartbeat-related power, inter-trial coherence, and functional connectivity increased during exhalation compared to inhalation, particularly in the alpha and theta frequency bands. These effects were primarily localized to right fronto-centro-parietal electrodes. Furthermore, we identified interactive relationships between heartbeat-evoked potential and heartbeat-modulated cortical oscillations in the alpha band that predicted interoceptive accuracy. These relationships were independent of cardiac physiology and were absent in the exteroceptive task. We proposed a model of cardio-respiratory interactions within the framework of interoceptive predictive coding, suggesting that these interactions occur at multiple levels of the interoceptive hierarchy: peripheral, brainstem, and cortical. Our interpretation highlights the role of heartbeat-related alpha-band modulations in enhancing the precision-weighting of cardiac prediction errors, thereby facilitating attentional allocation to interoceptive signals and the suppression of task-irrelevant distractors, particularly during exhalation.

neuroscience↗

bioRxiv2024

Bayesian Prior Uncertainty and Surprisal Elicit Distinct Neural Patterns During Sound Localization in Dynamic Environments

Estimating the location of a stimulus is a key function in sensory processing, and widely considered to result from the integration of prior information and sensory input according to Bayesian principles. A deviation of sensory input from the prior elicits surprisal, depending on the uncertainty of the prior. While this mechanism is increasingly understood in the visual domain, much less is known about its implementation in audition, especially regarding spatial localization. Here, we combined human EEG with computational modeling to study auditory spatial inference in a noisy, volatile environment and analyzed behavioral and neural patterns associated with prior uncertainty and surprisal. First, our results demonstrate that participants indeed used prior information during periods of stable environmental statistics, but showed evidence of surprisal and discarded prior information following environmental changes. Second, we observed distinct EEG activity patterns associated with prior uncertainty and surprisal in both the time- and time-frequency domain, which are in line with previous studies using visual tasks. Third, these EEG activity patterns were predictive of our participants sound localization error, response uncertainty, and prior bias on a trial-by-trial basis. In summary, our work provides novel behavioral and neural evidence for Bayesian inference during dynamic auditory localization.

neuroscience↗