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Biology subjects

Motala, A.

Publications and source records attributed to Motala, A..

3 recordsLinked to original sources

Multi-ancestry fine-mapping accounting for ancestral and environmental heterogeneity improves resolution and interpretation

Amongst genome-wide association studies (GWAS) across diverse populations, allelic effect heterogeneity may arise due to differences in genetic ancestry and environmental exposures. This heterogeneity impacts the refinement of sets of potential causal variants underlying genetic associations through statistical fine-mapping. We introduce two multi-ancestry fine-mapping methods, MR-MEGAfm and env-MR-MEGAfm, allowing for multiple causal variants in a genomic region. Both methods integrate GWAS summary statistics and differing linkage disequilibrium from multiple cohorts; env-MR-MEGAfm additionally incorporates summary-level environmental covariates. Through simulations, we show that, when allelic heterogeneity is correlated with environmental exposures and ancestry, env-MR-MEGAfm yields improved resolution over MR-MEGAfm and similar resolution to SuSiEx. In twelve sex-stratified African GWAS of low-density lipoprotein cholesterol in 19,589 individuals, MR-MEGAfm and env-MR-MEGAFM (adjusting for urban status) identify five variants with posterior probability > 0.5 within two loci. One variant showed heterogeneity only due to ancestry, while three showed heterogeneity due only to urban status.

genetics↗

Neural signatures of engagement and event segmentation during story listening in background noise

Speech in everyday life is often masked by background noise, making comprehension effortful. Characterizing brain activity patterns when individuals listen to masked speech can help clarify the mechanisms underlying such effort. However, most previous research has focused on neural activity related to short, disconnected sentences that little resemble the more continuous, story-like spoken speech individuals typically encounter. In the current study, we used functional magnetic resonance imaging (fMRI) in humans (both sexes) to investigate how neural signatures of story listening change in the presence of masking by 12-talker babble noise. We show that, as speech masking increases, spatial and temporal activation patterns in auditory regions become more idiosyncratic to each listener. In contrast, spatial (and to some extent temporal) activity patterns in brain networks linked to effort (e.g. cinguloopercular network involving the anterior insula and anterior cingulate) are more similar across listeners when speech is highly masked and less intelligible, suggesting shared neural processes. Moreover, at times during stories when one meaningful event ended and another began, neural activation increased over extensive regions in frontal, parietal, and medial cortices. This event-boundary response appeared little affected by background noise, suggesting that listeners process meaningful units and, in turn, the gist in naturalistic, continuous speech even when it is masked somewhat by background noise. Overall, the current data may indicate that people stay engaged and cognitive processes associated with naturalistic speech processing remain intact under moderate levels of background noise, whereas auditory processing becomes more idiosyncratic to each listener. Significance statementThis functional imaging study investigates how neural signatures of story listening change in the presence of masking multi-talker babble noise. We show that, as speech masking increases, auditory activity patterns become more idiosyncratic to each listener. Spatial activation patterns in effort-related regions (anterior insula, cingulate) become more similar across listeners when speech is strongly masked, indicating shared neural representations. Neural activation also increased at times when one meaningful story event ended and another began. This event-boundary response appeared little affected by moderate levels of background noise, suggesting that listeners process meaningful units in continuous speech even as background babble reduces speech intelligibility. The data indicate that many cognitive processes associated with listening to spoken stories remain intact under background noise.

neuroscience↗

Comparable human spatial memory distortions in physical, desktop virtual and immersive virtual environments

Boundaries define regions of space and are integral to episodic memories. The impact of boundaries on spatial memory and neural representations of space has been extensively studied in freely-moving rodents. But less is known in humans and many prior studies have employed desktop virtual reality (VR) which lacks the body-based self-motion cues of the physical world, diminishing the potentially strong input from path integration to spatial memory. We replicated a desktop-VR study testing the impact of boundaries on spatial memory (Hartley et al., 2004) in a physical room (2.4m x 2.4m, 2m tall) by having participants (N = 27) learn the location of a circular stool and then after a short delay replace it where they thought they had found it. During the delay, the wall boundaries were either expanded or contracted. We compared performance to groups of participants undergoing the same procedure in a laser-scanned replica in both desktop VR (N = 44) and freely-walking head mounted display (HMD) VR (N = 39) environments. Performance was measured as goodness of fit between the spatial distributions of group responses and seven modelled distributions that prioritised different metrics based on boundary geometry or walking paths to estimate the stool location. The best fitting model was a weighted linear combination of all the geometric spatial models, but an individual model derived from place cell firing in Hartley et al. 2004 also fit well. High levels of disorientation in all three environments prevented detailed analysis on the contribution of path integration. We found identical model fits across the three environments, though desktop VR and HMD-VR appeared more consistent in spatial distributions of group responses than the physical environment and displayed known variations in virtual depth perception. Thus, while human spatial representation appears differentially influenced by environmental boundaries, the influence is similar across virtual and physical environments. Despite differences in body-based cue availability, desktop and HMD-VR allow a good and interchangeable approximation for examining human spatial memory in small-scale physical environments.

neuroscience↗