Biology subjects

Griffiths, T.

Publications and source records attributed to Griffiths, T..

12 recordsLinked to original sources

bioRxiv2026

Neural Bases for Working Memory of Natural Sound Textures

Holding sound objects in mind is critical to understanding the sound world around us. Auditory texture perception is thought to rely on extracting statistical properties of sounds over time, raising the question of how encoding duration influences subsequent maintenance of auditory texture information. We investigated this question using behavioural performance and fMRI while participants performed two delayed match-to-sample tasks: a texture discrimination and a comparison loudness discrimination task. In the texture task, participants judged whether two sequentially presented sounds belonged to the same texture type, whereas in the loudness task, participants judged whether the sounds, drawn from the same texture type, had the same loudness. Stimuli were presented for either 0.1s or 2s. Discrimination sensitivity increased with duration in both tasks, but more strongly for texture discrimination. fMRI analysis revealed distinct effects of duration on univariate and multivariate activity in the auditory cortex and medial temporal lobe (MTL) during maintenance. We found no univariate duration effect in the auditory cortex during maintenance, but multivariate patterns encoded texture category more strongly for longer stimuli, regardless of task. In contrast, MTL activity was modulated by sound duration in both tasks, but there was no effect of duration on texture category decoding. There was a task effect in MTL where multivariate patterns in posterior hippocampal and parahippocampal regions distinguished texture from loudness tasks following 2s stimuli. Together, these findings show effects of duration on sound texture representations during maintenance and that MTL representations reflect the behavioural context in which that information is maintained.

neuroscience↗

bioRxiv2026

Near real-time data on the human neutralizing antibody landscape to influenza virus as of early 2026 to inform vaccine-strain selection

Twice each year, a decision is made on whether to update the strains included in the seasonal influenza vaccine to better match the most recent circulating viral strains. To characterize the antigenic properties of current seasonal influenza A strains to inform the upcoming decision about which strains to include in the 2026-2027 Northern Hemisphere vaccine, here we perform high-throughput sequencing-based neutralization assays using a library of 57 H3N2 and 34 H1N1 influenza hemagglutinins reflecting the circulating diversity of strains in late 2025 to early 2026. We assay this library against 302 human sera collected in late 2025. The resulting data set encompasses 27,409 titers, and provides a near real-time portrait of the human neutralizing antibody landscape against influenza virus. We find that many human sera have lower titers against the K subclade of H3N2 and the D.3.1.1 subclade of H1N1; these subclades have recently become dominant among their respective subtypes. Our measurements also reveal variability in titers to different subvariants within the K subclade of H3N2, with titers especially low to subclade K strains with additional mutations in antigenic regions D and E. We make all our data and accompanying visualizations publicly available to enable their use in vaccine-strain selection and analyses of influenza evolution and immunity.

microbiology↗

bioRxiv2025

Transcranial ultrasound stimulation selectively enhances fronto-temporal context-guided memory

There is substantial scientific interest in advancing knowledge on the control mechanisms supporting adaptive memory and improving approaches that can enhance cognition through brain stimulation. We implemented a non-invasive focal Transcranial Ultrasound Stimulation (TUS) approach with known longer-lasting post-stimulation effects in two rhesus macaques performing a novel context-dependent memory-sequencing task implemented on multiple touchscreens within their home units. Consistently in both monkeys, TUS to the anterior, but not posterior, medial temporal lobe enhanced performance under stable memory-sequencing contexts. TUS to the medial prefrontal cortex, on the other hand, selectively improved performance when contexts were unstable and the monkey needed to adapt to both a change in context and temporal sequence. These findings provide positive causal evidence of a functional dissociation within fronto-temporal memory circuits and pave the way for advancing non-invasive approaches to improve cognitive function and the study of neural circuits under focal enhancement across species. IMPACT STATEMENTTranscranial ultrasound stimulation of the prefrontal-hippocampal network selectively enhances context-guided memory in macaques, demonstrating that non-invasive brain stimulation can causally improve, rather than only disrupt, memory circuits.

neuroscience↗

bioRxiv2025

Brain Representations of Natural Sound Statistics

Natural sound textures (e.g., rain, crackling fire) are perceptually defined by time-averaged summary statistics. While previous studies have examined neural responses to natural sounds, little is known regarding the neural processing of the statistics underlying these sounds. To study neuronal correlates of these statistics, we measured brain responses to synthetic sound textures in which statistical structure was systematically varied while preserving the texture category. Using two fMRI experiments (males and females), we examined neural responses along the ascending auditory pathway, within auditory cortex and medial temporal lobe (MTL) regions implicated in pattern analysis. In Experiment 1, we parametrically varied the full set of texture statistics, creating sounds with different levels of naturalness. In Experiment 2, we selectively manipulated high-level statistics (cochlear skewness and kurtosis, cochlear and modulation correlations) while holding low-level statistics (cochlear mean and modulation power) constant. Increasing texture naturalness produced graded increases in BOLD responses across bilateral primary and nonprimary auditory cortex in both experiments, although overall responses were weaker in Experiment 2. This reduction suggests that low-level statistics contribute substantially to response magnitude, even though higher-order statistics are sufficient to elicit graded responses. We also observed modulation in MTL regions, including entorhinal cortex, in Experiment 1. Moreover, functional connectivity between hippocampus and auditory cortex increased for more degraded (less natural) textures, suggesting a modulatory rather than representational role for MTL in texture processing. Together, these findings show that sensitivity to texture statistics is distributed across the auditory cortex and highlight MTL-auditory interactions when texture structure is ambiguous. Significant StatementNatural sound textures such as rain or crackling fire are perceptually defined by time-averaged summary statistics that support efficient auditory perception, yet how the human brain represents these statistics remains unclear. Using fMRI and synthetic sound textures in which statistical structure was systematically manipulated, we found that both primary and nonprimary auditory cortex were sensitive to texture statistics, exhibiting a graded and distributed representation of these acoustic features. We also observed increased functional connectivity between the hippocampus and auditory regions when texture structure was degraded or the sounds were unnatural. Together, these results indicate that sound texture statistics are encoded across multiple levels of auditory cortex and further suggest a modulatory role for hippocampus under conditions of heightened perceptual uncertainty.

neuroscience↗

bioRxiv2025

High-throughput neutralization measurements correlate strongly with evolutionary success of human influenza strains

Human influenza viruses rapidly acquire mutations in their hemagglutinin (HA) protein that erode neutralization by antibodies from prior exposures. Here, we use a sequencing-based assay to measure neutralization titers for 78 recent H3N2 HA strains against a large set of children and adult sera, measuring [~]10,000 total titers. There is substantial person-to-person heterogeneity in the titers against different viral strains, both within and across age cohorts. The growth rates of H3N2 strains in the human population in 2023 are highly correlated with the fraction of sera with low titers against each strain. Notably, strain growth rates are less correlated with neutralization titers against pools of human sera, demonstrating the importance of population heterogeneity in shaping viral evolution. Overall, these results suggest that high-throughput neutralization measurements of human sera against many different viral strains can help explain the evolution of human influenza.

evolutionary biology↗

bioRxiv2025

Brain bases for navigating acoustic features

Whether physical navigation shares neural substrates with mental travel in other behaviourally relevant domains is debated. With respect to sound, pure-tone working memory in humans elicits hippocampal as well as auditory cortical and inferior frontal activity, and rodent work suggests that hippocampal cells that usually track an animals physical location can also map to tone frequency when task-relevant. We generated a sound dimension based on the density of random-frequency tones in a stack, resulting in a percept ranging from low- ("beepy") to high-density ("noisy"). We established that unlike tone frequency, which listeners automatically associate with vertical position, this density dimension elicited no consistent spatial mapping. During functional magnetic resonance imaging, human participants held in mind the density of a series of tone stacks and, after a short maintenance period, adjusted further stacks to match the target ("navigation"). Density of the currently heard sound was represented most strongly in bilateral non-primary auditory cortex, specifically bilateral planum polare, while density of the maintained target was represented in right anterior hippocampus and left inferior temporal gyrus. Encoding and maintenance activity in bilateral hippocampus, inferior frontal gyrus, planum polare and posterior cingulate was positively associated with subsequent navigation success. Bilateral inferior frontal gyrus and hippocampus were among regions with elevated activity during adjustment, compared to a parity-judgment condition with closely matched acoustics and motor demands. Bilateral orbitofrontal cortex was more active when navigation was toward a target density than when participants adjusted density in a control condition with no particular target. We find that self-initiated travel along a non-spatial auditory dimension engages a brain system overlapping with that supporting physical navigation. Key PointsO_LIWork in rodents suggests that navigation in physical space and the active analysis of sounds share a neural substrate in the hippocampus, supporting the use of common computational mechanisms. C_LIO_LIWe examined the human brain system for navigation through an acoustic environment to a remembered target. C_LIO_LIIn addition to high-level auditory cortex we demonstrate involvement of the hippocampus in acoustic navigation along with other sites in frontal and cingulate cortex that also support physical navigation. C_LI

neuroscience↗

bioRxiv2024

Predicting speech-in-noise ability with static and dynamic auditory figure-ground analysis using structural equation modelling

Auditory figure-ground paradigms assess the ability to extract a foreground figure from a random background, a crucial part of central hearing. Previous studies have shown that the ability to extract static figures (with fixed frequencies) predicts real-life listening: speech-in-noise ability. In this study we assessed both fixed and dynamic figures: the latter comprised component frequencies that vary over time like natural speech. 159 participants (aged 18-79) with a range of peripheral hearing sensitivity were studied. We used hierarchal linear regression and structural equation modelling to examine how well speech-in-noise ability (for words and sentences) could be predicted by age, peripheral hearing, and static and dynamic figure-ground. Regression demonstrated that in addition to the audiogram and age, the low-frequency dynamic figure-ground accounted for significant variance of speech-in-noise, higher than the static figure-ground. The structural models showed that a combination of all types of figure-ground tasks predicted speech-in-noise with a higher effect size than the audiogram or age. Age influenced word perception in noise directly but sentence perception indirectly via effects on peripheral and central hearing. Overall, this study demonstrates that dynamic figure-ground explains more variance of real-life listening than static figure-ground, and the combination of both predicts real-life listening better than hearing sensitivity or age.

neuroscience↗

bioRxiv2021

A specific relationship between musical sophistication and auditory working memory

Musical engagement may be associated with better listening skills, such as the perception of and working memory for notes, in addition to the appreciation of musical rules. The nature and extent of this association is controversial. In this study we assessed the relationship between musical engagement and both sound perception and working memory. We developed a task to measure auditory perception and working memory for sound using a behavioural measure for both, precision. We measured the correlation between these tasks and musical sophistication based on a validated measure (the Goldsmiths Musical Sophistication Index) that can be applied to populations of both musicians and non-musicians. The data show that musical sophistication accounts for 21% of the variance in the precision of working memory for frequency in an analysis that accounts for age and non-verbal intelligence. Musical sophistication was not significantly associated with the precision of working memory for amplitude modulation rate or with the precision of perception of either acoustic feature. The work supports a specific association between musical sophistication and working memory for sound frequency.

neuroscience↗

bioRxiv2020

Structures of the stator complex that drives rotation of the bacterial flagellum

The bacterial flagellum is the proto-typical protein nanomachine and comprises a rotating helical propeller attached to a membrane-embedded motor complex1. The motor consists of a central rotor surround by stator units that couple ion flow across the cytoplasmic membrane to torque generation. Here we present the structures of stator complexes from multiple bacterial species, allowing interpretation of the extensive body of data on stator mechanism. The structures reveal an unexpected asymmetric A5B2 subunit assembly in which the five A subunits enclose the two B subunits. Comparison to novel structures of other ion-driven motors indicates that this A5B2 architecture is fundamental to bacterial systems that couple energy from ion-flow to generate mechanical work at a distance, and suggests that such events involve rotation in the motor structures.

biochemistry↗

bioRxiv2019

Paradoxical role of AT-rich interactive domain 1A in restraining pancreatic carcinogenesis

Background & AimsARID1A is postulated to be a tumor suppressor gene owing to loss-of-function mutations in human pancreatic ductal adenocarcinomas (PDAC). However, its role in pancreatic pathogenesis is not clear despite recent studies using genetically engineered mouse (GEM) models. We aimed at further understanding of its direct functional role in PDAC, using a combination of GEM model, PDAC cell lines. MethodsPancreas-specific mutant Arid1a-driven GEM model (Ptf1a-Cre;KrasG12D;Arid1af/f or "KAC") was generated by crossing Ptf1a-Cre;KrasG12D ("KC") mice with Arid1af/f mice and characterized histologically with timed necropsies. Arid1a was also deleted using CRISPR-Cas9 system in established PDAC cell lines to study the immediate effects of Arid1a loss in isogenic models. Cells lines with or without Arid1a expression were developed from respective autochthonous PDAC GEM models, compared functionally using various culture assays, and subjected to RNA-sequencing for comparative gene expression analysis. DNA damage repair was analyzed in cultured cells using immunofluorescence and COMET assay. ResultsArid1a is critical for early progression of mutant Kras-driven pre-malignant lesions into PDAC, as evident by lower Ki-67 and higher apoptosis staining in "KAC" as compared to "KC" mice. Enforced deletion of Arid1a in established PDAC cell lines caused suppression of cellular growth and migration, accompanied by compromised DNA damage repair. Despite early development of relatively indolent cystic precursor lesions called intraductal papillary mucinous neoplasms (IPMNs), a subset of "KAC" mice developed aggressive PDAC in later ages. PDAC cells obtained from older autochthonous "KAC" mice revealed epigenetic changes underlying the various compensatory mechanisms to overcome the growth suppressive effects of Arid1a loss. ConclusionsArid1a is an essential survival gene whose loss impairs cellular growth, and thus, its expression is critical during early stages of pancreatic tumorigenesis in mouse models.

cancer biology↗

bioRxiv2019

Multivoxel codes for representing and integrating acoustic features in human cortex

Using fMRI and multivariate pattern analysis, we determined whether acoustic features are represented by independent or integrated neural codes in human cortex. Male and female listeners heard band-pass noise varying simultaneously in spectral (frequency) and temporal (amplitude-modulation [AM] rate) features. In the superior temporal plane, changes in multivoxel activity due to frequency were largely invariant with respect to AM rate (and vice versa), consistent with an independent representation. In contrast, in posterior parietal cortex, neural representation was exclusively integrated and tuned to specific conjunctions of frequency and AM features. Direct between-region comparisons show that whereas independent coding of frequency and AM weakened with increasing levels of the hierarchy, integrated coding strengthened at the transition between non-core and parietal cortex. Our findings support the notion that primary auditory cortex can represent component acoustic features in an independent fashion and suggest a role for parietal cortex in feature integration and the structuring of acoustic input.\n\nSignificance statementA major goal for neuroscience is discovering the sensory features to which the brain is tuned and how those features are integrated into cohesive perception. We used whole-brain human fMRI and a statistical modeling approach to quantify the extent to which sound features are represented separately or in an integrated fashion in cortical activity patterns. We show that frequency and AM rate, two acoustic features that are fundamental to characterizing biological important sounds such as speech, are represented separately in primary auditory cortex but in an integrated fashion in parietal cortex. These findings suggest that representations in primary auditory cortex can be simpler than previously thought and also implicate a role for parietal cortex in integrating features for coherent perception.

neuroscience↗

bioRxiv2019

‘Normal’ hearing thresholds and fundamental auditory grouping processes predict difficulties with speech-in-noise perception

Understanding speech when background noise is present is a critical everyday task that varies widely among people. A key challenge is to understand why some people struggle with speech-in-noise perception, despite having clinically normal hearing. Here, we developed new figure-ground tests that require participants to extract a coherent tone pattern from a stochastic background of tones. These tests dissociated variability in speech-in-noise perception related to mechanisms for detecting static (same-frequency) patterns and those for tracking patterns that change frequency over time. In addition, elevated hearing thresholds that are widely considered to be normal explained significant variance in speech-in-noise perception, independent of figure-ground perception. Overall, our results demonstrate that successful speech-in-noise perception is related to audiometric thresholds, fundamental grouping of static acoustic patterns, and tracking of acoustic sources that change in frequency. Crucially, measuring both peripheral (audiometric thresholds) and central (grouping) processes is required to adequately assess speech-in-noise deficits.

neuroscience↗