Biology subjects

Darki, F.

Publications and source records attributed to Darki, F..

10 recordsLinked to original sources

bioRxiv2026

Distinct roles for DNA- and RNA-sensing immune pathways in control of genital HSV-2 infection and restriction of neuroinvasion

Early control of viral infection is thought to rely on pattern-recognition receptors (PRRs) that induce interferons (IFNs) and leukocyte recruitment, but how distinct PRRs coordinate mucosal antiviral defense remains unclear. We show that both the DNA-sensing cGAS-STING pathway and the RNA-sensing RLR-MAVS pathway are required for protection upon genital herpes simplex virus type 2 (HSV-2) infection. cGAS deficiency increased infection-induced pathology in both epithelial and submucosal compartments, whereas MAVS deficiency primarily affected the epithelium. Spatial proteomics and regional transcriptomics revealed that cGAS was essential for early epithelial TBK1 activation, expression of IFN-stimulated genes and recruitment and activation of myeloid and lymphoid cells to the epithelium. While MAVS was essential for full TBK1 activation it had limited impact on the induced IFN response. However, MAVS sustained basal epithelial expression of the antiviral factors IFITM1 and 3, which exert antiviral activity against HSV-2. Notably, cGAS deficiency impaired submucosal IFN responses and enabled viral spread into this tissue, enabling infection of intervening neurons and dissemination to the central nervous system. These findings define coordinated, compartment-specific innate defense against infections.

immunology↗

bioRxiv2025

Auditory and visual object processing in olfactory cortex of individuals with life-long olfactory deprivation

The traditional view of modality-specific brain organization has been challenged by demonstrations of cross-modal processing, i.e. the activation of sensory cortex by atypical sensory input. An alternative theory suggests that rather than specializing simply in different sensory modalities, different parts of the cortex can specialize in different types of tasks. We recently addressed this question in the olfactory domain, showing that in normosmic individuals, the primary olfactory cortex (piriform cortex) responds to unimodal auditory and visual objects, regardless of how strongly they are associated with an odor. Here, we assess whether previous olfactory experience is a prerequisite for this cross-modal processing in the piriform cortex, using a unique group of individuals born without a sense of smell (congenital anosmia; CA; n = 30). First, we were able to confirm the presence of clear visual and auditory activations in the piriform cortex of these sensory deprived individuals. As compared to normosmic controls (n = 30), these activations and associated functional connectivity, both within the piriform cortices and between piriform cortex and other regions, were altered in a modality dependent way. Our results show that life-long absence of olfactory input does not impede cross-modal activations by visual and auditory objects in the piriform cortex and are compatible with the idea of a task-based rather than modality-specific organization of this brain region.

neuroscience↗

bioRxiv2025

Limited Effects of Isolated Congenital Anosmia on Cerebral White Matter Morphology

Lack of sensory input is associated with alterations in brain morphology; mainly in or near cerebral regions normally devoted to processing of the missing sense. We have in multiple studies demonstrated that the only consistent morphological finding within the gray matter of individuals born without the sense of smell (isolated congenital anosmia; ICA), are changes in or near the olfactory sulcus. For the connecting tissue of the brain, the white matter (WM), previous studies have yielded inconsistent findings. Here, we show that individuals with ICA (n=49) exhibit alterations in WM volume as compared to age- and sex-matched controls. Consistent evidence from both voxel-based morphometry and multi-voxel pattern analysis shows that individuals with ICA show decreased WM in areas surrounding the olfactory sulcus. Importantly, no WM alterations were found in areas surrounding the olfactory (piriform) cortex. In contrast to congenital sensory loss in other systems, we show that morphological alterations due to lifelong olfactory deprivation are limited. Alterations are primarily localized around the olfactory sulcus and likely due to the absence of olfactory bulbs. A possible explanation for the lack of major morphological alterations in individuals with congenital anosmia is that the olfactory regions may be recruited for non-olfactory functions.

neuroscience↗

bioRxiv2025

The olfactory bulb reflects structural plasticity within a genetically stable olfactory network

The olfactory bulb (OB), the first central relay of the olfactory pathway, plays a critical role in odor perception and exhibits remarkable structural plasticity shaped by environmental influences. This raises a fundamental question about the extent to which the structure of the OB is genetically determined. While both OB volume and function have been implicated in a range of neurodegenerative and neuropsychiatric disorders, such as Parkinsons disease, schizophrenia, and depression, all of which involve known genetic risk factors, the heritability of the OB structure remains poorly understood. Here, we investigated the heritability of OB volume and the broader olfactory network architecture in a large sample of healthy young adults (n = 941; aged 22-35 years), including monozygotic and dizygotic twin pairs. Using a deep learning-based segmentation model, we first automatically segmented OB volumes and then employed a support vector machine framework to classify zygosity based on within-pair morphological similarity. The OB volume alone showed weak classification performance in distinguishing between monozygotic and dizygotic twins, suggesting limited heritability. However, integrating OB volume with morphometric features from olfactory-associated brain regions, including the hippocampus, parahippocampal gyrus, entorhinal cortex, and medial orbitofrontal cortices, substantially improved classification performance. This effect was specific to the olfactory network, underscoring the distributed nature of genetic influence in this system. These findings suggest that the OB, despite being a highly plastic and environmentally responsive structure, is embedded within a genetically coordinated neural network.

neuroscience↗

bioRxiv2025

Methodological determinants of signal quality in electrobulbogram recordings

The electrobulbogram (EBG) is a new, non-invasive method for measuring the functional activity of the human olfactory bulb (OB). To date, the EBG has been used to assess how the OB process odor identity, valence, intensity, and it has shown promise as an early biomarker for Parkinsons disease. However, current implementation of the EBG method depends on several methodological components, including subject specific co-registration of electrode positions through neuronavigation and EEG source reconstruction, which may limit accessibility for many research groups. In this study, we test the quality and reliability of the OB signal under different configurations to potentially remedy this. Specifically, we compare six EBG setups that vary in the use of subject-specific T1 scans versus a template head model, co-registered versus template electrode positions, and individualized versus template-based OB location. Our results indicate that strongest EBG signals are obtained when using subject-specific T1 scans in combination with co-registered electrode positions. However, we obtained significant EBG activity even when using a fully template-based configuration. Our anatomical analysis of OB location of 941 individuals reveals that in 86% of cases, the OB is centered within the spatial resolution bounds of the EEG source dipole, supporting the feasibility of detecting olfactory bulb signals without precise individual anatomical mapping using template coordinates. These findings suggest that while subject-specific configurations enhance signal quality, the EBG method remains robust enough to yield meaningful results even with less complex setups. This enables a broader adoption of the EBG method in both clinical and research settings.

neuroscience↗

bioRxiv2024

Tactile stimulations reduce or promote the segregation of auditory streams: psychophysics and modelling

Auditory stream segregation plays a crucial role in understanding the auditory scene. This study investigates the role of tactile stimulation in auditory stream segregation through psychophysics experiments and a computational model of audio-tactile interactions. We examine how tactile pulses, synchronized with specific tones in a sequence of interleaved high- and low-frequency tones (ABA-triplets), influence the likelihood of perceiving integrated or segregated auditory streams. Our findings reveal that tactile pulses synchronized with specific tones enhance perceptual segregation, while pulses synchronized with both tones promote integration. Based on these findings, we developed a dynamical model that captures interactions between auditory and tactile neural circuits, including recurrent excitation, mutual inhibition, adaptation, and noise. The proposed model shows excellent agreement with the experiment. Model predictions are validated through psychophysics experiments. In the model, we assume that selective tactile stimulation dynamically modulates the tonotopic organization within the auditory cortex. This modulation facilitates segregation by reinforcing specific tonotopic responses through single-tone synchronization while smoothing neural activity patterns with dual-tone alignment to promote integration. The model offers a robust computational framework for exploring cross-modal effects on stream segregation and predicts neural behaviour under varying tactile conditions. Our findings imply that cross-modal synchronization, with carefully timed tactile cues, could improve auditory perception with potential applications in auditory assistive technologies aimed at enhancing speech recognition in noisy settings.

neuroscience↗

bioRxiv2023

Whither unisensory olfactory cortex: processing of visual and auditory stimuli in olfactory cortex, independently of odor associations

Primary sensory cortices have been demonstrated to process sensory input from non-preferred sensory modalities, e.g. primary visual cortex reacting to auditory stimulation, bringing their presumed sensory specificity into question. Whether this reflects processing of the non-preferred stimulus per se or originates from cross-modal associations is debated. Visual/auditory objects typically have strong reciprocal associations; hence, it is difficult to address this question in these modalities. Here, we attempt to dissociate between the two competing hypotheses of whether this form of activation in primary cortices is caused by unisensory processing or cross-modal associations by turning to the olfactory system where cross-modal associations are generally weaker. Using unisensory visual and auditory objects with odor associations ranging from none to strong, we show that the posterior piriform cortex, an area known to process odor objects, is activated by both sounds and pictures of objects. Critically, this activation is independent of the objects odor associations, thereby demonstrating that the activity is not due to cross-modal associations. Using a Floyd-Warshall algorithm, we further show that the amygdala mediate condition-relevant information between the posterior piriform cortex and both the auditory and visual object-oriented cortices. Importantly, we replicate past findings of clear crossmodal processing in the visual and auditory systems. Our study demonstrates processing of non-olfactory input in olfactory cortices that is independent of cross-modal associations and contributes to a more nuanced view of modality specificity in olfactory, auditory, and visual cortices.

neuroscience↗

bioRxiv2023

Lifelong olfactory deprivation-dependent cortical reorganization restricted to orbitofrontal cortex

Prolonged sensory deprivation has repeatedly been linked to cortical reorganization. We recently demonstrated that individuals with congenital anosmia (CA, complete olfactory deprivation since birth) have seemingly normal morphology in piriform (olfactory) cortex despite profound morphological deviations in the orbitofrontal cortex (OFC), a finding contradictory to both the known effects of blindness on visual cortex and to the sparse literature on brain morphology in anosmia. To establish whether these unexpected findings reflect the true brain morphology in CA, we first performed a direct replication of our previous study. Individuals with CA (n=30) were compared to age and sex matched controls (n=30) using voxel- and surface-based morphometry. The replication results were near identical to the original study: bilateral clusters of group differences in the OFC, including CA atrophy around the olfactory sulci and volume increases in the medial orbital gyri. Importantly, no group differences in piriform cortex were detected. Subsequently, to assess any subtle patterns of group differences not detectable by our mass-univariate analysis, we explored the data from a multivariate perspective. Combining the newly collected data with data from the replicated study (CA=49, Control=49) we performed support vector machine classification based on gray matter volume. In line with the mass-univariate analyses, the multivariate analysis could accurately differentiate between the groups in bilateral OFC (75-96% accuracy), whereas the classification accuracy in piriform cortex was at chance level. Our results suggest that despite lifelong olfactory deprivation, piriform (olfactory) cortex is morphologically unaltered and the morphological deviations in CA are confined to the OFC.

neuroscience↗

bioRxiv2022

Hierarchical processing underpins competition in tactile perceptual bistability

Ambiguous sensory information can lead to spontaneous alternations between perceptual states, recently shown to extend to tactile perception. The authors recently proposed a simplified form of tactile rivalry which evokes two competing percepts for a fixed difference in input amplitudes across antiphase, pulsatile stimulation of the left and right fingers. This study addresses the need for a tactile rivalry model that captures the dynamics of perceptual alternations and that incorporates the structure of the somatosensory system. The model features hierarchical processing with two stages; a first stage resolves perceptual competition, leading to perceptual alternations; and a second stage encodes perceptual interpretations. The first stage could be located downstream of brainstem nuclei and the second stage could be located within the primary somatosensory cortex (area 3b). The model captures dynamical features specific to the tactile rivalry percepts and produces general characteristics of perceptual rivalry: input strength dependence of dominance times (Levelts proposition II), short-tailed skewness of dominance time distributions and the ratio of distribution moments. The presented modelling work leads to experimentally testable predictions. The same hierarchical model could generalise to account for percept formation, competition and alternations for bistable stimuli that involve pulsatile inputs from the visual and auditory domains. Author summaryPerceptual ambiguity involving the touch sensation has seen increased recent interest. It provides interesting opportunity to explore how our perceptual experience is resolved by dynamic computations in the brain. We recently proposed a simple form of tactile rivalry where stimuli consisted of antiphase sequences of high and low intensity pulses delivered to the right and left index fingers. The stimulus can be perceived as either one simultaneous pattern of vibration on both hands, or as a pattern of vibrations that jumps from one hand to the other, giving a sensation of apparent movement. During long presentation of the stimuli, ones perception switches every 5-20 seconds between these two interpretations, a phenomenon called tactile perceptual bistability. This study presents the first computational model for tactile bistability and is based on the structure of sensory brain areas. The model captures important characteristics of perceptual interpretations for tactile rivalry. We offer predictions in terms of how left-right tactile intensity differences are encoded and propose a location for the encoding of perceptual interpretations in sensory brain areas. The model provides a generalisable framework that can make useful predictions for future behavioural experiments with tactile and other types of stimuli.

neuroscience↗

bioRxiv2020

Perceptual rivalry with vibrotactile stimuli

In perceptual rivalry, ambiguous sensory information leads to dynamic changes in the perceptual interpretation of fixed stimuli. This phenomenon occurs when participants receive sensory stimuli that support two or more distinct interpretations; this results in spontaneous alternations between possible perceptual interpretations. Perceptual rivalry has been widely studied across different sensory modalities including vision, audition and, to a limited extent, in the tactile domain. Common features of perceptual rivalry across various ambiguous visual and auditory paradigms characterise the randomness of switching times and their dependence on input strength manipulations (Levelts propositions). It is still unclear whether general characteristics of perceptual rivalry are preserved with tactile stimuli. This study aims to introduce a simple tactile stimulus capable of generating perceptual rivalry and explores whether general features of perceptual rivalry from other modalities extend to the tactile domain.

neuroscience↗