Biology subjects

Li, S.-C.

Publications and source records attributed to Li, S.-C..

11 recordsLinked to original sources

bioRxiv2026

Aging and reorganization of the neural hierarchy underlying action perception: older adults prioritize affective-communicative information

Everyday action perception unfolds in complex contexts, requiring coordinated processing from low-level visual information to higher-level inferences about action types and social interactions. Aging is accompanied by sensory and cognitive changes, raising the question of how these processes may be altered. Here, we combined action similarity judgments with analyses of time-resolved and source-localized brain activity measured with magnetoencephalography (MEG) to investigate age differences in action perception when younger and older adults viewed naturalistic actions. Using cross-validated variance partitioning within a multivariate representational framework, three key findings were uncovered. First, affective-communicative features predicted similarity judgments better than, and independent of, visual and action-related features in both age groups. Second, neural processes in both groups followed a hierarchy from visual to action-related and affective-communicative features and recruited similar functional regions. However, older adults showed delayed visual processing but earlier affective-communicative processing, indicating selective prioritization rather than uniform slowing of subprocesses. Third, when sensory uncertainty was increased through visual blurring, older adults showed hierarchical reorganization, with affective-communicative features emerging earlier than action-related features, whereas younger adults preserved the original hierarchy. Together, these findings unveil adapted information prioritization in healthy aging, whereby socially meaningful information increasingly guides action perception when sensory input becomes unreliable.

neuroscience↗

bioRxiv2026

First community challenge for automated virus taxonomy

The rapid rate of virus discovery renders manual curation by taxonomy experts increasingly impractical, creating a need for reliable software that can reproducibly assign viral contigs to taxa at all fifteen ranks of the virus taxonomy. We led an open community challenge for the computational taxonomic classification of viruses and assembled a dataset of virus sequences combining expert-curated and metagenomic sequences. Seventeen teams contributed a total of thirty-four automated, fully reproducible classification pipelines. Most tools correctly assigned viruses belonging to established species, genera, or families, but viruses that are unclassified at those lower ranks remain challenging. This study provides datasets, open-source software, novel approaches, and recommendations to benchmark computational taxonomic classification of viruses, and support organizing the many viruses discovered in big omics data.

microbiology↗

bioRxiv2026

Retest Reliability of Task-related fMRI BOLD Signals during Sequential Decision Making

IntroductionFunctional magnetic resonance imaging (fMRI) is widely used to study neural processes of behavior, but evaluations of test-retest reliability (TRR) of task-related blood-oxygen-level-dependent (BOLD) responses are scarce for many cognitive tasks. Such information is particularly important for longitudinal and intervention research. The ability to learn associations between choices and outcomes across decision stages is crucial for daily behavior. We assessed the measurement reliability of behavioral performance and fMRI BOLD signals during value-based sequential decision making to evaluate the TRR of task-relevant regions for future research on non-invasive brain stimulations. MethodsTwenty healthy adults (22 to 40 years) completed two task-fMRI sessions, at least 2 weeks apart. During scanning, participants performed two variants of a three-stage Markov decision task with conditions varied in temporal contingency (immediate vs. delayed) and magnitude of choice outcomes (high vs. low). Both sessions were conducted under sham tDCS via a focal 3 x 1 montage targeting left dorsolateral prefrontal cortex (DLPFC). TRR was assessed using intraclass correlation coefficients (ICC) with a two-way mixed-effects consistency model for decision performance and task-related fMRI signals at voxel level and summarized in key regions defined by the extended Human Connectome Project atlas (HCPex). ResultsDecision performance was lower with delayed than immediate outcomes (p < 0.001). Higher outcome magnitude improved performance (p < 0.001). Decision performance increased across learning bins (p < 0.001). The behavioral TRR was in the moderate to good level (ICC(3,1) = 0.744 for accuracy; ICC(3,1) = 0.788 for reaction time). At the whole-brain level, contrasting brain activities in delayed with immediate condition revealed suprathreshold cluster peaks in several frontal-parietal (e.g., orbitofrontal, bilateral dorsolateral prefrontal, and medial parietal cortices) and striatal regions (e.g., bilateral putamen). Voxel-wise ICCs revealed variable but often moderate-to-good TRR across task-relevant regions, with stronger reliability in several striatal, orbitofrontal, and left dorsolateral prefrontal parcels, and more variable reliability across anterior cingulate and medial prefrontal parcels. ConclusionThese results from a 2-session tDCS sham-sham stimulation study establish the validity of using the three-stage Markov decision task in future studies about intervention effects on the frontal-parietal-striatal network.

neuroscience↗

bioRxiv2026

The Interplay between Language Development, Short-Term Memory, and Auditory Associative Word Learning in Younger and Older Children

Auditory associative word learning has been shown in infants and proven to be a difficult task in young adults, where learning is only successful under specific conditions. In order to better understand the transition from successful infant auditory associative word learning to the challenging adult learning, we tested 5-6-year-olds and 9-10-year-olds in a sequential associative task to investigate their ability in associating novel pseudowords with environmental sounds. Additionally, we explored how episodic short-term memory recognition, language development, sex, and musical training affect behavioral and electrophysiological measures of word learning. EEG data were collected to assess word learning in an initial training phase (consistent vs. inconsistent pairings) and a subsequent testing phase (matching vs. violated pairings) with additional button-press reactions for behavioral learning data. While learning effects were seen in the first half of the training phase in younger children, no early effects of learning were found in older children. Only musically trained 9-10-year-olds indicated word learning in the second half of the training phase. In the testing phase, only non-musically trained 9-10-year-olds revealed trend-level N400-like responses. Short-term memory (auditory-verbal, auditory-nonverbal, and visual-nonverbal) and language development improved with age, but only visual-nonverbal short-term memory recognition was positively correlated with improved auditory associative word learning. Unlike cross-modal visual associative word learning, our results, together with earlier findings in infants and young adults, suggest a difficulty in auditory associative word learning beyond infancy, which is sustained from childhood to young adulthood.

neuroscience↗

bioRxiv2026

Harmonizing the stimulation dose of focal tDCS across target sites

Non-invasive brain stimulation is an established tool for modulating neural activity that holds promise for advancing both cognitive neuroscience and clinical interventions. Focal transcranial direct current stimulation (tDCS), using center-surround electrode montages, enables more region-specific targeting. Although computational models can simulate individual electric fields, no existing approach enables the prospective individualization of electrode placement while standardizing the dose across targeted brain regions. In the current preparatory methodological study, we present a modeling-based framework that harmonizes the electric field strength between different target regions at the group level, but preserves inter-individual variability. This enables systematic examination of dose-response relationships and their regional differences. Positioning of the center-surround electrode montages is individualized to ensure focusing of the electric field on the target regions. We started by defining brain targets for eight cognitive and motor functions using MRI data from 43 participants. Using field simulations, we then estimated a group-average field strength in the target regions that had led to behavioral and physiological effects in prior tDCS studies (resulting in 0.2 V/m). The radii of the center-surround montages were optimized for each target region to achieve the intended field strength while maximizing focality. Validation in an independent sample (n=53) confirmed that the intended target field strength is achieved on average for new participants. The described computational tools are made available as open-source software, allowing other researchers to apply our individualization framework with parameters (target regions and target field strengths) tailored to their specific research questions; and are currently being implemented in a multi-center study involving approximately 1,000 datasets.

neuroscience↗

bioRxiv2025

Observing being touched enhances the neural processing and perception of digital gentle stroking

Observing touch activates brain regions similar to those activated by experiencing actual touch, suggesting that visual information can cross-modally influence tactile perception. In this electroencephalography (EEG) study, we investigated how viewing visual displays of an arm being touched may affect the perception and processing of digitally rendered touch patterns designed to resemble either stroking or tapping. Thirty-one participants experienced touch patterns delivered to their left forearm via a wearable sleeve while viewing either a photo of an arm or spatiotemporally aligned videos of an arm being touched in synchrony with either of the two touch patterns. Continuity and pleasantness ratings of touch stimuli were higher for stroking than for tapping. Correlations between continuity and pleasantness ratings were stronger when touch was accompanied by videos of touch than by the photo of an arm. Analysis of evoked brain responses revealed visual modulation of touch processing at centroparietal electrodes beginning at around 0.9 s, with the cross-modal effects diverging between stroking and tapping at about 1.6 s. Furthermore, the interaction effects of cross-modal influences between stroking and tapping at the neural level positively correlated with the visual modulation of pleasantness ratings in two right frontal clusters at around 1.4 s and 1.8 s. These results suggest that observing touch influences the perception and processing of touch through initial sensory integration at centroparietal sites, followed by later frontal valuation processes. This extends previous findings on affective touch by demonstrating that visual inputs can cross-modally shape the hedonic evaluation of digitally actuated touch.

neuroscience↗

bioRxiv2025

Stay or Stray: Lpar1 regulates neutrophil retention and epidermal homeostasis in early zebrafish development

Neutrophils are the most abundant myeloid cells in the vertebrate innate immune system and play a crucial role in host defense. Dysregulated release from hematopoietic tissue or excessive recruitment to inflamed sites is associated with immunopathologies, including chronic inflammation and recurrent infections. Lysophosphatidic acid (LPA) is a bioactive lipid that signals through a family of G protein-coupled receptors (LPAR1-6). Among these, LPA-LPAR1 signaling is activated in inflamed tissues and is known to modulate neutrophil infiltration during inflammatory responses. However, its role in neutrophil dynamics during early development remains unclear. Here, we report a novel function of Lpar1 in regulating neutrophil behavior during early zebrafish development. In Lpar1-deficient embryos, we observed a significant increase in neutrophil dispersal from the caudal hematopoietic tissue (CHT) at 3 days post-fertilization (dpf), with most dispersed neutrophils infiltrating the skin and contributing to elevated inflammatory signaling. Prior to dispersal, Lpar1-deficient embryos exhibited increased apoptosis of superficial epidermal cells and reduced expression of cxcl12a, a key retention signal for neutrophils in the CHT. Together, these findings highlight an essential role for Lpar1 in maintaining neutrophil retention and epidermal homeostasis during early development, thereby limiting inappropriate inflammation. SUMMARY STATEMENTThis work identifies a new role for a known inflammatory receptor in coordinating immune cell retention and skin stability during early development.

developmental biology↗

bioRxiv2023

Brain oscillatory processes related to sequence memory in healthy older adults

Sequence memory is subject to age-related decline, but the underlying processes are not yet fully understood. We analyzed electroencephalography (EEG) in 21 healthy older (60-80 years) and 26 young participants (20-30 years) and compared time-frequency spectra and theta-gamma phase-amplitude-coupling (PAC) during encoding of the order of visually presented items. In older adults, desynchronization in theta (4-8 Hz) and synchronization in gamma (30-45 Hz) power did not distinguish between subsequently correctly and incorrectly remembered trials, while there was a subsequent memory effect for young adults. Theta-gamma PAC was modulated by item position within a sequence for older but not young adults. Specifically, position within a sequence was coded by higher gamma amplitude for successive theta phases for later correctly remembered trials. Thus, deficient differentiation in theta desynchronization and gamma oscillations during sequence encoding in older adults may reflect neurophysiological correlates of age-related memory decline. Furthermore, our results indicate that sequences are coded by theta-gamma PAC in older adults, but that this mechanism might lose precision in aging.

neuroscience↗

bioRxiv2021

L-DOPA enhances hippocampal directionsignals in younger and older adults

Previous studies indicate a role of dopamine in hippocampus-dependent spatial navigation. Although neural representations of direction are an important aspect of spatial cognition, it is not well understood whether dopamine directly affects these representations, or only impacts other aspects of spatial brain function. Moreover, both dopamine and spatial cognition decline sharply during age, raising the question which effect dopamine has on directional signals in the brain of older adults. To investigate these questions, we used a double-blind cross-over L-DOPA/Placebo intervention design in which 43 younger and 37 older adults navigated in a virtual spatial environment while undergoing functional magnetic resonance imaging (fMRI). We studied the effect of L-DOPA, a DA precursor, on fMRI activation patterns that encode spatial walking directions that have previously been shown to lose specificity with age. This was done in predefined regions of interest, including the early visual cortex, retrosplenial cortex, and hippocampus. Classification of brain activation patterns associated with different walking directions was improved in the hippocampus and the retrosplenial cortex following L-DOPA administration. This suggests that DA enhances the specificity of neural representations of walking direction in these areas. In the hippocampus these results were found in both age groups, while in the RSC they were only observed in younger adults. Taken together, our study provides evidence for a mechanistic link between DA and the specificity of neural responses during spatial navigation. Significance StatementThe sense of direction is an important aspect of spatial navigation, and neural representations of direction can be found throughout a large network of space-related brain regions. But what influences how well these representations track someones true direction? Using a double-blind cross-over L-DOPA/Placebo intervention design, we find causal evidence that the neurotransmitter dopamine impacts the fidelity of direction selective neural representations in the human hippocampus and retrosplenial cortex. Interestingly, the effect of L-DOPA was either equally present or even smaller in older adults, despite the well-known age related decline of dopamine. These results provide novel insights into how dopamine shapes the neural representations that underlie spatial navigation.

neuroscience↗

bioRxiv2019

Effects of Aging on the Encoding of Spatial Direction in the Human Brain

Human aging is characterized by impaired spatial cognition and reductions in the distinctiveness of category-specific fMRI activation patterns. Yet, little is know about age-related decline in neural distinctiveness of spatial information. Here, we asked whether neural tuning functions of walking direction are broadened in older versus younger adults. To test this idea, we developed a novel method that allowed us to investigate changes in fMRI-measured pattern similarity while participants navigated in different directions in a virtual spatial navigation task. We expected that directional tuning functions would be broader in older adults, and thus activation patterns that reflect neighboring directions would be less distinct as compared to non-adjacent directions. Because loss of distinctiveness leads to more confusions when information is read out by downstream areas, we analyzed predictions of a decoder trained on these representations and asked (1) whether decoder confusions between two directions increase proportionally to their angular similarity, (2) and how this effect may differ between age groups. Evidence for tuning-function-like signals was found in the retrosplenial complex and primary visual cortex. Significant age differences in tuning width, however, were only found in the primary visual cortex, suggesting that less precise visual information could lead to worse directional signals in older adults. Yet, age differences in visual tuning were not related to behavior. Instead, directional information encoded in RSC correlated with memory on task. These results shed new light on neural mechanisms underling age-related spatial navigation impairments and introduce a novel approach to measure tuning specificity using fMRI.

neuroscience↗

bioRxiv2018

Diminished pre-stimulus alpha-lateralization suggests compromised self-initiated attentional control of auditory processing in old age

Older adults experience difficulties in daily situations that require flexible information selection in the presence of multiple competing sensory inputs, like for instance multi-talker situations. Modulations of rhythmic neural activity in the alpha-beta (8-30 Hz) frequency range in posterior brain areas have been established as a cross-modal neural correlate of selective attention. However, research linking compromised auditory selective attention to changes in rhythmic neural activity in aging is sparse.\n\nWe tested younger (n = 25; 22-35 years) and older adults (n = 26; 63-76 years) in an attention modulated dichotic listening task. In this, two streams of highly similar auditory input were simultaneously presented to participants' both ears (i.e., dichotically) while attention had to be focused on the input to only one ear (i.e. target) and the other, distracting information had to be ignored.\n\nWe here demonstrate a link between severely compromised auditory selective attention in aging and a partial reorganization of attention-related rhythmic neural responses. In particular, in old age we observed a shift from a self-initiated, preparatory modulation of alpha rhythmic activity to an externally driven, response in the alpha-beta range. Critically, moment-to-moment fluctuations in the age-specific patterns of self-initiated and externally driven lateralized rhythmic activity were tied to selective attention. We conclude that adult age difference in spatial selective attention likely derive from a functional reorganization of rhythmic neural activity within the aging brain.

neuroscience↗