bioRxiv Science⌕ Search

Biology subjects

Sandhu, M. S.

Publications and source records attributed to Sandhu, M. S..

6 recordsLinked to original sources

Generalization in motor learning: learning bimanual coordination with one hand

The ability to coordinate movements between the hands is crucial for many daily tasks. However, the precise mechanisms governing the storage and utilization of bimanual movement and the distinct contributions of each limb in this process are currently not fully understood. Two key questions persist: 1) How is the neural representation of bimanual coordination stored in the brain, and 2) How is the information governing bimanual coordination shared between hemispheres? In this investigation, we used a virtual partner (VP) to systematically address these issues by allowing the same coordination pattern (CP) to be acquired with unimanual and bimanual movements. More specifically, we used four experimental groups: unimanual (left, right) VP, bimanual, and control conditions. For each condition, retention and transfer tests were administered immediately and 6 hours after the initial practice. The control condition employed the same protocol as unimanual conditions without practice. As anticipated, performance after practice and during retention sessions indicated that all groups learned to perform the target CP. Furthermore, generalization from unimanual to bimanual occurred when the same type of visual feedback (VF) was provided. Interestingly, the absence of VF impaired motor generalization from unimanual to bimanual condition unless the participants initially practiced the task bimanually. Taken together, our results demonstrated that both limbs could access the memory representation of the CP. However, this globally shared representation appeared to be encoded in the visual-spatial domain. The conditions without VF underscored the importance of proprioception in forming a motor representation in intrinsic coordinates. NEW & NOTEWORTHYConventional views on acquiring bimanual skills stress the need for simultaneous engagement of both hands. However, our study challenges this notion by demonstrating that the coordination pattern learned in unimanual conditions significantly boosts subsequent bimanual coordination--a novel approach to skill acquisition. Yet, this advantage diminishes without visual feedback, resulting in a breakdown of the intended bimanual coordination, highlighting the limitations of relying solely on unimanual practice.

neuroscience↗

MRI mapping of hemodynamics in the human spinal cord

Impaired spinal cord vascular function contributes to numerous neurological pathologies, making it important to be able to noninvasively characterize these changes. Here, we propose a functional magnetic resonance imaging (fMRI)-based method to map spinal cord vascular reactivity (SCVR). We used a hypercapnic breath-holding task to evoke a systemic vasodilatory response during concurrent blood oxygenation level-dependent fMRI. SCVR amplitude and hemodynamic delay were mapped at the group level as proof-of-concept of the approach, and in two highly-sampled participants to probe feasibility/stability of individual SCVR mapping. Across the group and individuals, a strong ventral SCVR amplitude was initially observed without accounting for local regional variation in the timing of the vasodilatory response. Shifted breathing traces were used to account for temporal differences in the vasodilatory response across the cord, producing maps of SCVR delay. These maps demonstrate distinct gray matter regions concordant with territories of arterial supply. The SCVR fMRI methods described here enable robust mapping of spatiotemporal hemodynamic properties of the human spinal cord. This noninvasive approach has the potential to provide early insight into pathology-driven vascular changes in the cord, which may precede and predict future irreversible tissue damage and guide the treatment of several neurological pathologies involving the spine.

physiology↗

Transcriptomics and chromatin accessibility in multiple African population samples

Mapping the functional human genome and impact of genetic variants is often limited to European-descendent population samples. To aid in overcoming this limitation, we measured gene expression using RNA sequencing in lymphoblastoid cell lines (LCLs) from 599 individuals from six African populations to identify novel transcripts including those not represented in the hg38 reference genome. We used whole genomes from the 1000 Genomes Project and 164 Maasai individuals to identify 8,881 expression and 6,949 splicing quantitative trait loci (eQTLs/sQTLs), and 2,611 structural variants associated with gene expression (SV-eQTLs). We further profiled chromatin accessibility using ATAC-Seq in a subset of 100 representative individuals, to identity chromatin accessibility quantitative trait loci (caQTLs) and allele-specific chromatin accessibility, and provide predictions for the functional effect of 78.9 million variants on chromatin accessibility. Using this map of eQTLs and caQTLs we fine-mapped GWAS signals for a range of complex diseases. Combined, this work expands global functional genomic data to identify novel transcripts, functional elements and variants, understand population genetic history of molecular quantitative trait loci, and further resolve the genetic basis of multiple human traits and disease.

genomics↗

Spatial distribution of hand-grasp motor task activity in spinal cord functional magnetic resonance imaging

Upper extremity motor paradigms during spinal cord functional magnetic resonance imaging (fMRI) can provide insight into the functional organization of the cord. Hand-grasping is an important daily function with clinical significance, but previous studies of similar squeezing movements have not reported consistent areas of activity and are limited by sample size and simplistic analysis methods. Here, we study spinal cord fMRI activation using a unimanual isometric hand-grasping task that is calibrated to participant maximum voluntary contraction (MVC). Two task modeling methods were considered: (1) a task regressor derived from an idealized block design (Ideal) and (2) a task regressor based on the recorded force trace normalized to individual MVC (%MVC). Across these two methods, group motor activity was highly lateralized to the hemicord ipsilateral to the side of the task. Activation spanned C5-C8 and was primarily localized to the C7 spinal cord segment. Specific differences in spatial distribution are also observed, such as an increase in C8 and dorsal cord activity when using the %MVC regressor. Furthermore, we explored the impact of data quantity and spatial smoothing on sensitivity to hand-grasp motor task activation. This analysis shows a large increase in number of active voxels associated with the number of fMRI runs, sample size, and spatial smoothing, demonstrating the impact of experimental design choices on motor activation.

neuroscience↗

Insights into human genetic variation and population history from 929 diverse genomes

Genome sequences from diverse human groups are needed to understand the structure of genetic variation in our species and the history of, and relationships between, different populations. We present 929 high-coverage genome sequences from 54 diverse human populations, 26 of which are physically phased using linked-read sequencing. Analyses of these genomes reveal an excess of previously undocumented private genetic variation in southern and central Africa and in Oceania and the Americas, but an absence of fixed, private variants between major geographical regions. We also find deep and gradual population separations within Africa, contrasting population size histories between hunter-gatherer and agriculturalist groups in the last 10,000 years, a potentially major population growth episode after the peopling of the Americas, and a contrast between single Neanderthal but multiple Denisovan source populations contributing to present-day human populations. We also demonstrate benefits to the study of population relationships of genome sequences over ascertained array genotypes. These genome sequences are freely available as a resource with no access or analysis restrictions.

genomics↗

An Unexpectedly Complex Architecture for Skin Pigmentation in Africans

Fewer than 15 genes have been directly associated with skin pigmentation variation in humans, leading to its characterization as a relatively simple trait. However, by assembling a global survey of quantitative skin pigmentation phenotypes, we demonstrate that pigmentation is more complex than previously assumed with genetic architecture varying by latitude. We investigate polygenicity in the Khoe and the San, populations indigenous to southern Africa, who have considerably lighter skin than equatorial Africans. We demonstrate that skin pigmentation is highly heritable, but that known pigmentation loci explain only a small fraction of the variance. Rather, baseline skin pigmentation is a complex, polygenic trait in the KhoeSan. Despite this, we identify canonical and non-canonical skin pigmentation loci, including near SLC24A5, TYRP1, SMARCA2/VLDLR, and SNX13 using a genome-wide association approach complemented by targeted resequencing. By considering diverse, under-studied African populations, we show how the architecture of skin pigmentation can vary across humans subject to different local evolutionary pressures.\n\nHighlightsO_LISkin pigmentation in Africans is far more polygenic than light skin pigmentation in Eurasians.\nC_LIO_LIKhoeSan[§] populations, which diverged early in human prehistory from other populations, have lightened skin pigmentation compared to equatorial Africans.\nC_LIO_LISkin color is highly heritable in the KhoeSan, but pigmentation variability is not well explained by previously discovered pigmentation genes.\nC_LIO_LIWe perform the first GWAS for pigmentation in African KhoeSan populations and identify canonical pigmentation loci near TYRP1 and in SLC24A5, as well as novel associations surrounding SMARCA2 and other genes.\nC_LI

genetics↗