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James, O.

Publications and source records attributed to James, O..

4 recordsLinked to original sources

Gain-controlled reconfiguration of long-range coupling explains visibility-dependent spatiotemporal neural coding dynamics

Numerous studies demonstrate the widespread cortical engagement in conscious and unconscious processing1-5, yet the mechanistic principle that reorganizes spatiotemporal neural dynamics across different levels of conscious access remains unclear. We addressed this using a personalized, connectome-constrained large-scale biophysical model of whole-brain source-imaged electroencephalography (EEG) dynamics recorded from participants who reported the orientation of a backward-masked Gabor patch at four levels of visibility. The key control parameter in the model is the global input gain ({gamma}) to physiologically-grounded cell populations, defined operationally such that higher {gamma} denotes weaker effective global input, which reconfigures long-range couplings and thus modulates spatiotemporal neural dynamics. Fitted {gamma} maps showed higher gain in posterior regions and lower gain in frontal regions on visible trials, whereas the pattern was opposite on invisible trials - i.e., posterior regions received weaker and frontal regions stronger input under visibility, with the opposite under invisibility. This inversion of {gamma} map was observed in pyramidal, VIP, and PV populations, while supplementary pyramidal, SST, and PV time constant were invariant. The visibility-dependent reversal in gain topography mirrored the observed spatiotemporal neural coding dynamics - under visibility, early occipital-to-frontal dynamic coding switched to stable coding, whereas in invisible condition, frontal-dominant stable coding emerged early with attenuated dynamic coding. Simulations generated from the fitted parameters reproduced the observed spatiotemporal neural coding dynamics, supporting a gain-control axis - with pyramidal input efficacy as the principal readout and coordinated VIP/PV modulation - that selects between locally integrating and globally broadcasting regimes as visibility changes. Our results provide a bottom-up mechanistic account of differential perceptual processing depending on the degree of the stimulus awareness, offering insights into potentially resolving ongoing debates about theories of consciousness.

neuroscience↗

A proteomic map of B cell activation and its shaping by mTORC1, MYC and iron

Using high resolution quantitative mass spectrometry, we have explored how immune activation and the metabolic checkpoint kinase mTORC1 (mammalian target of rapamycin complex 1) regulate the proteome of B lymphocytes. B cell activation via the B cell receptor, CD40 and the IL4 receptor induced considerable re-modelling of the B cell protein landscape, with a 5-fold increase in total cellular protein mass within 24 hours of activation. Analysis of copy numbers per cell of >7,500 proteins revealed increases in the metabolic machinery that supports B cell activation and nutrient and amino acid transporters that fuel B cell biosynthetic capacity. Comparison of T cell-dependent versus T cell-independent B cell stimulation along with an analysis of the synergistic effects of stimuli, identified shared and unique impacts of stimuli and highlighted the drivers of B cell proteome remodelling. In addition, we reveal that mTORC1 controls activation-induced B cell growth and inhibiting mTORC1 impairs the expression of amino acid transporters that fuel B cell protein production. We also show that mTORC1 activity regulates the expression of the transcription factor MYC and the transferrin receptor CD71. Blocking MYC activity phenocopied mTORC1 inhibition in many ways including impaired CD71 expression, while limiting iron availability during B cell activation impaired B cell growth and protein synthesis. This work provides a detailed map of naive and immune activated B cell proteomes and a greater understanding of the cellular machinery that directs B cell phenotypes. This work also provides new insights into the role of mTORC1, MYC and iron in regulating activation-induced proteome remodelling and protein production in B cells.

immunology↗

Frontal engagement in perceptual integration under low subjective visibility

We investigated how spatiotemporal neural dynamics underlying perceptual integration changed with the degree of conscious access to a set of backward-masked pacman-shaped inducers that generated the percept of an illusory triangle. We kept the stimulus parameters at a fixed near-threshold level throughout the experiment and recorded electroencephalography from participants who reported the orientation and subjective visibility of the illusory triangle on each trial. Our multivariate pattern analysis revealed that posterior and central regions initially used dynamic neural code and later switched to stable neural code. The transition from dynamic to stable neural code in posterior region occurred increasingly later and eventually disappeared with decreasing conscious access. Anterior region primarily used stable neural code which waned with decreasing conscious access, but increased at below-median visibility and remained even when stimulus awareness was minimal. These results demonstrate differential spatiotemporal neural dynamics underlying perceptual integration depending on conscious access and emphasize a unique role of anterior region in processing integrated shape information especially under low subjective visibility.

neuroscience↗

RELATIONSHIP BETWEEN PARENTAL AGE AND SEVERITY OF OROFACIAL CLEFTS

OBJECTIVESThis study aims to investigate the relationship between paternal age, maternal age, and both on the severity of orofacial clefts. DESIGNThis was a retrospective study of cases which were subjects clinically diagnosed with non-syndromic cleft lip and/or palate (CL/P). Data was obtained from the AFRICRAN project database on Nigerian non-syndromic orofacial cleft cases. SETTINGThe samples for cases in this study were obtained at the Cleft clinic of Oral and Maxillofacial surgery at the Lagos University Teaching Hospital, Lagos. OUTCOMEPrimary outcome measure is severity of orofacial clefts and secondary outcome measure is to evaluate the effect of parental age in determining the incidence of left or right sided orofacial clefts. RESULTSThere is no statistical significant association between type of CL {+/-} P and parental age in young fathers (p=0.93). When old fathers are considered, percentage of complete (more severe) CL {+/-} P cases increases especially in old mothers and this was statistically significant (p=0.036). In old fathers, the risk of CL {+/-} P is increased (OR: 2.66, CI: 1.04-6.80) and also there is increased risk of developing right sided CL {+/-} P (OR: 1.61, CI: 1.0-2.59). There is reduced risk of isolated cleft palate in young fathers (OR: 0.36, CI: 0.07-1.71) but the risk increases when considering complete types (more severe) of isolated cleft palates (OR: 1.63, CI: 0.71-3.7) CONCLUSIONThe study shows a higher risk of CL {+/-} P is associated with increase fathers age.

genetics↗