Biology subjects

Allen, J. W.

Publications and source records attributed to Allen, J. W..

3 recordsLinked to original sources

bioRxiv2026

Physiological Oscillations of Lateral Ventricular Volume Revealed by Fast fMRI: Effects of Aging and Vigilance

Abstract Background: Cyclic ventricular deformation may contribute to CSF displacement. However, the physiological mechanisms underlying ventricular motion remain poorly understood. This study characterized physiological oscillations of lateral ventricular volume (LVV) and examined their associations with aging and vigilance. Methods: We analyzed two fast resting-state fMRI scans from 99 adults aged 35-82 years. The first scan was acquired during eyes-open wakefulness, followed by 30 min of eyes-closed rest and a second scan during eyes-closed drowsiness. LVV was estimated for each image volume using automated ventricular segmentation, yielding time-resolved volume measurements. Temporal variability was quantified using the standard deviation and coefficient of variation, and spectral power was quantified for low-frequency, respiratory, and cardiac oscillations. Age-related associations were assessed using multiple linear regression adjusted for sex. Awake-drowsy differences were assessed using paired t-tests. False discovery rate correction was applied for multiple comparisons in all analyses. Results: After quality-control exclusions, 97 participants were analyzed. LVV exhibited distinct low-frequency, respiratory, and cardiac oscillatory components. Respiratory and cardiac oscillations accounted for 37.7% and 38.4% of total physiological spectral power, respectively, compared with 23.9% for low-frequency oscillations. Mean lateral ventricular volume increased with age (FDR-adjusted p = 0.010), while respiratory and cardiac power also showed positive associations with age, although neither survived FDR correction (both FDR-adjusted p = 0.067). The transition to eyes-closed drowsiness was associated with greater LVV fluctuation magnitude, reflected by increases in standard deviation (FDR-adjusted p < 0.001) and coefficient of variation (FDR-adjusted p = 0.028) and accompanied by increased low-frequency (FDR-adjusted p < 0.001) and respiratory power (FDR-adjusted p = 0.015). Mean LVV and cardiac power did not change significantly between conditions. Conclusions: LVV exhibits prominent respiratory and cardiac oscillations in addition to low-frequency fluctuations, suggesting that ventricular dynamics reflect multiple physiological influences rather than a single dominant physiological driver. Aging was primarily associated with ventricular enlargement, whereas reduced vigilance was accompanied by increased LVV fluctuation magnitude, primarily reflected in increased low-frequency and respiratory power, without a change in mean LVV. Time-resolved LVV provides a complementary approach for investigating the physiological regulation of ventricular dynamics in health and disease. Keywords: Cerebrospinal fluid; Lateral ventricular volume; Fast fMRI; Physiological oscillations; Cardiac pulsation; Respiration; Low-frequency oscillations; Aging; Vigilance

bioengineering↗

bioRxiv2026

Time-Varying Directed Interactions in Functional Brain Networks: Modeling and Validation

Brain function depends on time-resolved directional organization: influence is continuously redistributed across regions, shaping who drives whom, when, and for how long. Yet dynamic neuroimaging has largely emphasized undirected fluctuations in functional connectivity, limiting biological interpretation of asymmetric interactions. Here we show that directed influence can be resolved into two biologically distinct signatures: strength, reflecting the efficacy of influence, and duration, reflecting its temporal extent. To test this principle, we developed sliding-window prediction correlation (SWpC), a framework for estimating these signatures in fMRI and related signals. Across simultaneous rat local field potential (LFP)-fMRI and human motor-task fMRI, strength more closely tracks neural-BOLD coupling and task-evoked reconfiguration, whereas duration captures temporally extended BOLD patterns more susceptible to hemodynamic timing. In post-concussion vestibular dysfunction, altered strength-duration profiles define reproducible vestibular-multisensory states and improve patient-control discrimination. Together, these findings support a general principle of dynamic brain organization spanning neurophysiology, behavior, and disease.

bioengineering↗

bioRxiv2025

Perturbational single-cell profiling of patient tumors defines lineage- and context-specific programs of innate immune resistance

AbstractDespite promise in preclinical models, most immuno-oncology drug candidates fail in clinical trials. These failures reflect limitations in our ability to directly model the response of human tumor and immune cells to immunotherapies. To address this gap and test the effect of innate immune agonists, we developed PERCEPT, an approach that uses ex vivo perturbational single-cell RNA sequencing to compare the response of immunomodulatory treatments with unstimulated controls directly in patient samples. Using PERCEPT, we tested cytokines and innate immune agonists in melanoma and Merkel cell carcinoma (MCC) and identified the dsRNA mimetic, RIG-I agonist, Stem Loop RNA (SLR) 14 as a powerful inducer of anti-viral states and enhancer of T cell activation. We compared transcriptional responder and non-responder patient samples and identified midkine (MDK), a multifunctional cytokine, as a potent repressor of IFN signaling in both tumor and immune cells. MDK expression dampened MHC-I presentation in human tumor cells and reduced activation of antigen-presenting cells, disrupting tumor immunity at multiple levels. In contrast to prior studies, we identified MDK as specifically enriched in neuroendocrine cancers such as MCC and small cell lung cancer compared with melanoma, suggesting the importance of lineage- and context-specific targeting. Our results demonstrate the utility of high-dimensional controlled perturbation of patient samples to identify mechanisms of innate immune response and resistance and demonstrate an actionable path towards clinical development of MDK-inhibiting therapies including FDA-approved ALK inhibitors in neuroendocrine cancers.

cancer biology↗