Biology subjects

Silva, A. B.

Publications and source records attributed to Silva, A. B..

5 recordsLinked to original sources

bioRxiv2023

Inhibitory control of speech production in the human premotor frontal cortex

Natural speech is full of starts and stops. Here, we studied the neural mechanisms that underlie the inhibitory control of speech, specifically the ability to stop speaking on demand. We recorded direct cortical activity while participants made continuous speech production and were given a visual cue to stop speaking. Neural recordings revealed activity in the premotor frontal cortex associated with speech stopping. Cortical sites showing stop activity were largely distinct from sites involved in active speech production or, more specifically, encoding articulatory movements. Electrocortical stimulation mapping at many premotor sites with stop activity caused involuntary speech arrest, an immediate inability to speak or vocalize. Furthermore, many speech arrest sites did not co-localize with neural activity correlating with speech motor planning or execution, contrary to this long-assumed function in clinical brain mapping. Together, these results suggest a previously unknown premotor cortical network that underlies the inhibitory control of speech, which has significant implications for understanding the dynamics of normal and altered speech production, as well as clinical brain mapping.

neuroscience↗

bioRxiv2021

White Matter Signals Reflect Information Transmission Between Brain Regions During Seizures

White matter supports critical brain functions such as learning and memory, modulates the distribution of action potentials, and transmits neural information between brain regions. Notably, neuronal cell bodies exist in deeper white matter tissue, neurotransmitter vesicles are released directly in white matter, and white matter blood-oxygenation level dependent (BOLD) signals are detectable across a range of different tasks--all appearing to reflect a dynamic, active tissue from which recorded signals can reveal meaningful information about the brain. Yet, the signals within white matter have largely been ignored. Here, we elucidate the properties of white matter signals using intracranial EEG in a bipolar montage. We show that such signals capture the communication between brain regions and differentiate pathophysiologies of epilepsy. In direct contradiction to past assumptions that white matter functional signals provide little value, we show that white matter recordings can elucidate brain function and pathophysiology. Broadly, white matter functional recordings acquired through implantable devices may provide a wealth of currently untapped knowledge about the neurobiology of disease.

neuroscience↗

bioRxiv2021

A Framework for Brain Atlases: Lessons from seizure Dynamics

Brain maps, or atlases, are essential tools for studying brain function and organization. The abundance of available atlases used across the neuroscience literature, however, creates an implicit challenge that may alter the hypotheses and predictions we make about neurological function and pathophysiology. Here, we demonstrate how parcellation scale, shape, anatomical coverage, and other atlas features may impact our prediction of the brains function from its underlying structure. We show how network topology, structure-function correlation (SFC), and the power to test specific hypotheses about epilepsy pathophysiology may change as a result of atlas choice and atlas features. Through the lens of our disease system, we propose a general framework and algorithm for atlas selection. This framework aims to maximize the descriptive, explanatory, and predictive validity of an atlas. Broadly, our framework strives to provide empirical guidance to neuroscience research utilizing the various atlases published over the last century.

neuroscience↗

bioRxiv2021

Direct tissue sensing reprograms TLR4+ Tfh-like cells inflammatory profile in the joints of rheumatoid arthritis patients

CD4+ T cells mediate rheumatoid arthritis (RA) pathogenesis through both antibody-dependent and independent mechanisms. It remains unclear how synovial microenvironment impinges on CD4+ T cells pathogenic functions. Here, we identified a TLR4+ follicular helper T (Tfh) cell-like population present in the blood and expanded in synovial fluid. Mechanistically, we unveiled that homotypic T-T cell interactions through non-cognate HLA-DR:TCR contacts regulate TLR4 expression on T cells. TLR4+ T cells possess a two-pronged pathogenic activity. Upon TCR and ICOS engagement, TLR4+ T cells produce IL-21, a cytokine known to sponsor antibody production. However, direct TLR4+ engagement on T cells, by endogenous ligands in the arthritic joint, reprograms them towards an IL-17 inflammatory profile compatible with tissue damage program. Blocking TLR4 signaling with a specific inhibitor impaired IL-17 production in response to synovial fluid recognition. Ex vivo, synovial fluid TLR4+ T cells produced IL-17, but not IL-21. TLR4+ T cells appear to uniquely reconcile an ability to promote systemic antibody production with a local synovial driven tissue damage program. TLR4+ T cells could constitute an attractive cellular target and predictive biomarker for erosive arthritis.

immunology↗

bioRxiv2018

Modulation of defence and iron homeostasis genes in rice roots by the diazotrophic endophyte Herbaspirillum seropedicae

Rice is staple food of nearly half the worlds population. Rice yields must therefore increase to feed ever larger populations. By colonising rice and other plants, Herbaspirillum spp. stimulate plant growth and productivity. However the molecular factors involved are largely unknown. To further explore this interaction, the transcription profiles of Nipponbare rice roots inoculated with Herbaspirillum seropedicae were determined by RNA-seq. Mapping the 104 million reads against the Oryza sativa cv. Nipponbare genome produced 65 million unique mapped reads that represented 13,840 transcripts each with at least two-times coverage. About 7.4 % (1,019) genes were differentially regulated and of these 256 changed expression levels more than two times. Several of the modulated genes encoded proteins related to plant defence (e.g. a putative probenazole inducible protein), plant disease resistance as well as enzymes involved in flavonoid and isoprenoid synthesis. Genes related to the synthesis and efflux of phytosiderophores (PS) and transport of PS-iron complexes were also induced by the bacteria. These data suggest that the bacterium represses the rice defence system while concomitantly activating iron uptake. Transcripts of H. seropedicae were also detected amongst which genes involved in nitrogen fixation, cell motility and cell wall synthesis were the most expressed.\n\nHighlightsRNASeq of H. seropedicae colonised rice roots showed remarkable regulation of defence, metal transport, stress and signalling genes. Fe-uptake genes were highly induced with implications in plant nutrition and immunity.

plant biology↗