Biology subjects

Nair, A. K.

Publications and source records attributed to Nair, A. K..

6 recordsLinked to original sources

bioRxiv2026

Divergent phenotypic and functional roles of human T follicular helper cells from infancy to adulthood

Antibody responses to T-dependent antigens are suboptimal in young children, yet the evolution of T follicular helper cell (Tfh) function across the human lifespan remains poorly defined. Using human tonsils, a physiologically relevant and abundant source of Tfh, we investigated age-associated differences in their repertoire and functional programs. Pediatric tonsils were enriched for cytokine-expressing Tfh subsets with increased clonal diversity and phenotypic plasticity. However, in response to influenza antigens, they exhibited reduced Th1 polarization, diminished IL-21 production, and limited B cell help. Across ages, high neutralizing flu antibody responses were associated with robust Tfh1 activation, which was ICOS dependent in adults but not in children. Interestingly, Tfh depletion strategies revealed enhanced Tfh differentiation from distinct precursors in pediatric donors, yet antibody responses during early life were less reliant on Tfh help. Together, these findings define developmentally programmed differences in Tfh differentiation and function with implications for pediatric vaccine design.

immunology↗

bioRxiv2026

A tonsil organoid model reveals Epstein-Barr virus infected germinal center B cell states during primary infection

Epstein-Barr virus (EBV) colonizes secondary lymphoid tissues to establish persistent infection and is strongly associated with malignancy and autoimmunity. Our understanding of EBV infection biology is hindered by a lack of models that capture infected B cell activity in the lymphoid tissue microenvironment. We therefore developed an EBV human tonsil organoid model to evaluate key B cell states and antiviral responses, including after primary infection. EBV promoted B cell differentiation into germinal center (GC)-like phenotypes and transcriptomic analyses highlighted numerous B cell transcriptional programs unique to EBV-infected cells. B cell receptor repertoire analysis revealed that most EBV-infected B cells underwent class switching but only rarely participated in somatic hypermutation. CD4 T cells, highly activated by organoid infection, limited EBV+ B cell outgrowth. Our findings demonstrate human tonsil organoids as a physiologically relevant model to investigate key aspects of EBV immunity and pathogenesis.

immunology↗

bioRxiv2025

EEG Phase Slips Reveal Detailed Brain Activity Patterns of Novice Vipassana Meditators During Decision Making Tasks

Our study adopted a novel approach, utilizing four biomarkers, namely EEG potentials, their first-order derivatives, and phase slip rates derived from each, to discern the differences between novice Vipassana (NVP) subjects and non-meditator controls (NMC). Phase slip rates are discontinuities in instantaneous phase that represent cortical phase transitions, indicating a significant change in the overall brain state. We employed 128-channel EEG data from eight NMC and eight NVP subjects, collected during a gamified protocol, to investigate object identification within a visual oddball paradigm. EEG was continuously acquired during the 50 trials for each subject. We retained 44 artifact-free trials per subject (the minimum common across all subjects) and computed within-subject averages. The EEGs were then averaged separately for NMC and NVP subjects. The EEG was filtered in the alpha band, and the phase was extracted using the Hilbert transform, unwrapped, and the phase slip rates were computed. A montage layout of electrodes was used to make the spatiotemporal plots of biomarkers. Our findings revealed that the spatiotemporal profiles of all four biomarkers differed significantly between the two groups of subjects. Furthermore, the NVP subjects demonstrated faster object recognition. These results not only provide a unique method to use phase slip rates to quantify cognitive differences between NMC and NVP subjects but also present a promising set of biomarkers for quantitative task-based EEG analyses.

neuroscience↗

bioRxiv2025

Similar States, Different Paths: Neurodynamics of diverse meditation techniques

Meditation encompasses diverse practices that train attention inward, in contrast to externally oriented task states. However, the neurodynamic features distinguishing meditative states from non-meditative states across traditions remain unclear. We analyzed high-density EEG data (N=170; 121 advanced meditators, 49 controls) across four traditions: Vipassana, Brahma Kumaris Raja Yoga, Heartfulness, and Isha Yoga. EEG features spanned oscillatory, aperiodic, nonlinear, and timescale components. Using random forest classifiers, we distinguished meditative from non-meditative states with robust classification performance (91%). Nonlinear features contributed the most, suggesting a core neurodynamic profile. Classification performance was higher in advanced meditators (92%) than in controls (85%), with distinct feature importance: nonlinear and aperiodic features dominated in meditators, and oscillatory and timescale features in controls. Each tradition showed distinct neurodynamic profiles, indicating technique-specific constellations. Our findings revealed shared yet distinct neurodynamic signatures across meditation techniques, suggesting that multiple neurodynamic pathways lead to meditative states.

neuroscience↗

bioRxiv2019

Simultaneous assessment of P50, MMN, ERN and P300 event-related potentials among patients with Schizophrenia - an exploratory study

PurposeP50 suppression (sensory gating or inhibition), MMN (mismatch negativity; bottom-up detection of change), ERN (error related negativity; conflict monitoring) and P300 (attention allocation and memory updating for salient events) are event related potentials (ERPs) widely reported to show abnormal cognitive functioning among patients with schizophrenia. In real-life scenarios the brain processing underlying these ERPs occur simultaneously, and yet prior ERP studies have evaluated them in isolation. The current study uses a novel paradigm that can examine these multiple ERPs simultaneously, and explore if the reported ERP deficits would hold true during a more realistic setting.\n\nMethodData from 21 patients with schizophrenia and 25 age- and gender-matched healthy controls were used, who underwent ERP recordings during the Assessing Neurocognition via Gamified Experimental Logic (ANGEL) paradigm. This is a gamified visual odd-ball paradigm that generates P300, the error responses generate ERN, and paired-tone audio distractors generate P50 and MMN. Peak-peak amplitude, mean amplitude and area-under-curve measures of ERP were measured at electrodes reflecting best morphology.\n\nResultsThough patients showed apparent ERP morphology differences relative to the controls, the standard ERP measures were comparable between groups, except for reduced ERN among patients. Interestingly, significant group differences were seen in N1-P2 complex suppression, despite comparable P50 suppression.\n\nContribution of the researchThe current study is the first to report multiple ERP component measures simultaneously evoked among patients with schizophrenia, and shows greater signs for impaired prediction mechanism. The findings of the study would provide a more ecologically valid evaluation of ERP-based cognitive functioning, and need to be replicated in a larger sample as well as other mental disorders.

neuroscience↗

bioRxiv2019

Schizophrenia patients show aberrant brain dynamics associated with gestalt-perception and corollary discharge: Reflections from ERP and fMRI findings

BackgroundSchizophrenia is a disorder of higher mental attributes, and is characterized by psychotic symptoms that are believed to involve a basic inability to make valid predictions about expected sensations and experiences. These have been reported separately while monitoring either externally generated environmental patterns (e.g. gestalt-perception) or self-generated sensory experiences (e.g. corollary-discharge). As the pathophysiology behind predictive dysfunction is better viewed as an aberration in brains functional synchrony, a whole brain assessment using electroencephalographic (EEG) event related potential (ERP) and functional magnetic resonance imaging (fMRI) techniques, would offer a wider perspective to brain network abnormalities in schizophrenia.\n\nMethodWe used our lab-developed game-based task which presents degraded two-tone images to assess gestalt-perception, and simultaneously alters the congruency between participants button-press response and its auditory feedback to assess corollary-discharge. In both patients with schizophrenia and age-matched healthy controls, we explored event-related changes in an EEG-ERP study (n=21 each) and whole brain functional connectivity changes in a fMRI study (patients,n=12; controls,n=16), using the same task.\n\nResultsPatients showed reduced event-related EEG dynamics during both the error-prediction conditions (gestalt-perception and corollary-discharge), which include reduction in average waveforms (around N170 and N1-P2 complex, respectively) and altered theta dynamics (power and phase). Source-level EEG measures were clustered around the cingulo-insular network. fMRI functional connectivity analysis also found the abnormality in these brain regions, forming significantly weak connections with right insular/opercular cortex.\n\nConclusionsThis is the first study to explore thalamo-cortical dysfunction hypothesis in schizophrenia by integrating prediction-error-coding during perception ( gestalt-perception) and action ( corollary-discharge) using two neuroimaging modalities (EEG-ERP and fMRI). Besides adding to the knowledgebase of schizophrenia research, our novel task design and findings on theta-oscillation could benefit in the development of effective neuromodulatory therapeutic tools for patients with schizophrenia such as neurofeedback and transcranial brain stimulation.

neuroscience↗