Biology subjects

Kessler, R.

Publications and source records attributed to Kessler, R..

7 recordsLinked to original sources

bioRxiv2026

Disambiguation of two-tone images reveals semantic contributions to object recognition in the EEG

Electrophysiological responses to visual objects carry information about stimulus identity and semantic category, but it remains difficult to know whether such information represents semantic knowledge or merely regularities in physical image features. Here, we presented two-tone images while recording EEG to dissociate the learned semantic concept from physical stimulus properties in the electrophysiological signal. Seventeen healthy participants completed a semantic disambiguation experiment with three phases: ambiguous two-tone images before disambiguation, their corresponding grayscale photographs, and the same two-tone images after disambiguation. We quantified representational change using Mahalanobis distances between EEG response patterns. After disambiguation, EEG responses to learned two-tone images became more similar to the response of their photo counterparts, indicating semantic enrichment of stimulus-specific representations. This effect emerged approximately 100 ms after stimulus onset and persisted across an extended time window. However, we found no evidence for an increase in semantic category-level responses after disambiguation. Furthermore, responses to spontaneously recognized two-tone images did not already show stronger alignment with the responses to their corresponding photo images before explicit visual disambiguation was performed. Together, these findings show that EEG can capture learned semantic modulations of responses to visually degraded stimuli, while also indicating that low-level visual properties dominate the representational structure. Two-tone images can therefore serve as a useful paradigm for probing semantic learning in the EEG, and may guide future research in children and patient populations whose ability to behaviorally confirm learning is limited.

neuroscience↗

bioRxiv2026

Representational similarity of hemodynamic brain responses to written and spoken words increases when learning to read

Learning to read requires binding auditory and visual information together, yet how the developing brain maps information across sensory modalities remains poorly understood. To shed light on this topic we employed functional magnetic resonance imaging to investigate hemodynamic brain responses during spoken and written word or pseudoword recognition in primary school children with different levels of reading experience. Audiovisual representational similarity of activation patterns in the inferior frontal gyrus, inferior parietal lobule, superior temporal gyrus, and temporo-occipital cortex, increased with school grade and this similarity was largest in the left posterior superior temporal gyrus. Our results suggest that learning to read is related to increasing neurophysiological similarity of auditory and visual word representations within canonical language areas.

neuroscience↗

bioRxiv2024

Electrophysiological decoding captures the temporal trajectory of face categorization in infants

The adult human brain rapidly distinguishes between faces at around 170 milliseconds after stimulus onset. In the developing brain, however, the time course of face discrimination is poorly understood. To shed light on this issue, we presented human and nonhuman primate faces to five to thirteen-month-old infants in an event-related electroencephalography experiment. Using time-resolved decoding based on logistic regression we detected above-chance discrimination of human faces from nonhuman faces in a time window starting at around 200 milliseconds, originating from occipito-temporal electrodes. There was no evidence, however, for above-chance discrimination of individual human or individual nonhuman faces. Moreover, using neural network-based decoding, we delivered the proof of principle that face categorization but not individuation can be detected even at the level of single participants. These results indicate that rapid face categorization emerges already in preverbal infants.

neuroscience↗

bioRxiv2022

Multi-ancestry GWAS of major depression aids locus discovery, fine-mapping, gene prioritisation, and causal inference

Most genome-wide association studies (GWAS) of major depression (MD) have been conducted in samples of European ancestry. Here we report a multi-ancestry GWAS of MD, adding data from 21 studies with 88,316 MD cases and 902,757 controls to previously reported data from individuals of European ancestry. This includes samples of African (36% of effective sample size), East Asian (26%) and South Asian (6%) ancestry and Hispanic/Latinx participants (32%). The multi-ancestry GWAS identified 190 significantly associated loci, 53 of them novel. For previously reported loci from GWAS in European ancestry the power-adjusted transferability ratio was 0.6 in the Hispanic/Latinx group and 0.3 in each of the other groups. Fine-mapping benefited from additional sample diversity: the number of credible sets with [≤]5 variants increased from 3 to 12. A transcriptome-wide association study identified 354 significantly associated genes, 205 of them novel. Mendelian Randomisation showed a bidirectional relationship with BMI exclusively in samples of European ancestry. This first multi-ancestry GWAS of MD demonstrates the importance of large diverse samples for the identification of target genes and putative mechanisms.

genetics↗

bioRxiv2020

Functional diversity of PFKFB3 splice variants in glioblastomas

Tumor cells tend to metabolize glucose through aerobic glycolysis instead of oxidative phosphorylation in mitochondria. One of the rate limiting enzymes of glycolysis is 6-phosphofructo-1-kinase, which is allosterically activated by fructose 2,6-bisphosphate which in turn is produced by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2/FBPase-2 or PFKFB). Mounting evidence suggests that cancerous tissues overexpress the PFKFB isoenzyme, PFKFB3, being causing enhanced proliferation of cancer cells. Initially, six PFKFB3 splice variants with different C-termini have been documented in humans. More recently, additional splice variants with varying N-termini were discovered the functions of which are to be uncovered. Glioblastoma is one of the deadliest forms of brain tumors. Up to now, the role of PFKFB3 splice variants in the progression and prognosis of glioblastomas is only partially understood. In this study, we first re-categorized the PFKFB3 splice variant repertoire to simplify the denomination. We investigated the impact of increased and decreased levels of PFKFB3-4 (former UBI2K4) and PFKFB3-5 (former variant 5) on the viability and proliferation rate of glioblastoma U87 and HEK-293 cells. The simultaneous knock-down of PFKFB3-4 and PFKFB3-5 led to a decrease in viability and proliferation of U87 and HEK-293 cells as well as a reduction in HEK-293 cell colony formation. Overexpression of PFKFB3-4 but not PFKFB3-5 resulted in increased cell viability and proliferation. This finding contrasts with the common notion that overexpression of PFKFB3 enhances tumor growth, but instead suggests splice variant-specific effects of PFKFB3, apparently with opposing effects on cell behaviour. Strikingly, in line with this result, we found that in human IDH-wildtype glioblastomas, the PFKFB3-4 to PFKFB3-5 ratio was significantly shifted towards PFKFB3-4 when compared to control brain samples. Our findings indicate that the expression level of distinct PFKFB3 splice variants impinges on tumorigenic properties of glioblastomas and that splice pattern may be of important diagnostic value for glioblastoma.

cancer biology↗

bioRxiv2019

The Ontogenetic Development of Hemispheric Lateralization During Face Processing: A Functional Magnetic Resonance Imaging Pilot Study in 7- to 9-Year-old Children

Face processing is mediated by a distributed neural network commonly divided into a \"core system\" and an \"extended system\". The core system consists of several, typically right-lateralized brain regions in the occipito-temporal cortex, including the occipital face area (OFA), the fusiform face area (FFA) and the posterior superior temporal sulcus (pSTS). It was recently proposed that the face processing network is initially bilateral and becomes right-specialized in the course of the development of reading abilities due to the competition between language-related regions in the left occipito-temporal cortex (e.g., the visual word form area) and the FFA for common neural resources.\n\nThe goal of the present pilot study was to prepare the basis for a larger follow-up study assessing the ontogenetic development of the lateralization of the face processing network. More specifically, we aimed on the one hand to establish a functional magnetic resonance imaging (fMRI) paradigm suitable for assessing activation in the core system of face processing in young children at the single subject level, and on the other hand to calculate the necessary group size for the planned follow-up study.\n\nTwelve children aged 7-9 years, and ten adults were measured with a face localizer task that was specifically adapted for children. Our results showed that it is possible to localize the core systems brain regions in children even at the single subject level. We further found a (albeit non-significant) trend for increased right-hemispheric lateralization of all three regions in adults compared to children, with the largest effect for the FFA (estimated effect size d=0.78, indicating medium to large effects). Using these results as basis for an informed power analysis, we estimated that an adequately powered (sensitivity 0.8) follow-up study testing developmental changes of FFA lateralization would require the inclusion of 18 children and 26 adults.

neuroscience↗

bioRxiv2018

Prospective Study of Polygenic Risk, Protective Factors, and Incident Depression Following Combat Deployment in US Army Soldiers

BackgroundWhereas genetic susceptibility increases risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could buffer against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.\n\nMethodsData were analyzed from 4,182 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at predeployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from the largest available MDD genome-wide association study. We first examined main effects of the MDD PRS and each protective factor on incident MDD. We then tested effects of each protective factor on incident MDD across strata of polygenic risk.\n\nResultsPolygenic risk showed a dose-response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.\n\nConclusionsPolygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion--an index of perceived support and morale--was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.

genetics↗