Biology subjects

Frederick, B.

Publications and source records attributed to Frederick, B..

4 recordsLinked to original sources

bioRxiv2025

Physiological Arousal as a Predominant Source of Individual Differences in Functional Brain Networks

Individual differences in brain network function and organization are promising targets for fMRI-based biomarkers in precision psychiatry, yet the sources of individual variability remain poorly understood. We show that arousal, assessed by systemic low-frequency oscillation (sLFO) amplitude in the fMRI signal, accounts for a substantial portion of variance in brain network properties (e.g.: R= 0.70 for default mode network (DMN)-dorsal attention connectivity; R= -0.63 for DMN dynamics). These relationships replicated across sessions, across independent samples, and when assessed with traditional arousal indices. Critically, associations persisted after sLFO denoising, indicating a genuine brain-physiology relationship rather than hemodynamic artifact. Pharmacological manipulation showed that drug-induced sLFO-assessed arousal changes were accompanied by corresponding shifts in network connectivity and dynamics. This work identifies arousal as a prominent determinant of variability in functional brain networks, providing a new perspective on brain-based individual differences while offering an approach to measure arousal directly from fMRI data.

neuroscience↗

bioRxiv2023

A Unified Physiological Process Links Global Patterns of Functional MRI, Respiratory Activity, and Autonomic Signaling

The brain is closely attuned to visceral signals from the bodys internal environment, as evidenced by the numerous associations between neural, hemodynamic, and peripheral physiological signals. We show that these brain-body co-fluctuations can be captured by a single spatiotemporal pattern. Across several independent samples, as well as single-echo and multi-echo fMRI data acquisition sequences, we identify widespread co-fluctuations in the low-frequency range (0.01 - 0.1 Hz) between resting-state global fMRI signals, neural activity, and a host of autonomic signals spanning cardiovascular, pulmonary, exocrine and smooth muscle systems. The same brain-body co-fluctuations observed at rest are elicited by arousal induced by cued deep breathing and intermittent sensory stimuli, as well as spontaneous phasic EEG events during sleep. Further, we show that the spatial structure of global fMRI signals is maintained under experimental suppression of end-tidal carbon dioxide (PETCO2) variations, suggesting that respiratory-driven fluctuations in arterial CO2 accompanying arousal cannot explain the origin of these signals in the brain. These findings establish the global fMRI signal as a significant component of the arousal response governed by the autonomic nervous system.

neuroscience↗

bioRxiv2022

A high throughput screen with a clonogenic endpoint to identify radiation modulators of cancer

Gomes, N. P., Frederick, B., Jacobsen, J. R., Chapnick. D. and Su, T. T. A high throughput screen with a clonogenic endpoint to identify radiation modulators of cancer. Radiat. Res. Clonogenic assays evaluate the ability of single cells to proliferate and form colonies. This process approximates the regrowth and recurrence of tumors after treatment with radiation or chemotherapy, and thereby provides a drug discovery platform for compounds that block this process. However, because of their labor-intensive and cumbersome nature, adapting canonical clonogenic assays for high throughput screening (HTS) has been challenging. We overcame these barriers by developing an integrated system that automates cell- and liquid-handling, irradiation, dosimetry, drug administration, and incubation. Further, we developed a fluorescent live-cell based automated colony scoring methodology that identifies and counts colonies precisely based upon actual nuclei number rather than colony area, thereby eliminating errors in colony counts caused by radiation induced changes in colony morphology. We identified 13 cell lines from 7 cancer types, where radiation is a standard treatment module, that exhibit identical radiation and chemoradiation response regardless of well format and are amenable to miniaturization into small-well HTS formats. We performed pilot screens through a 1584 compound NCI Diversity Set library using two cell lines representing different cancer indications. Radiation modulators identified in the pilot screens were validated in traditional clonogenic assays, providing proof-of-concept for the screen. The integrated methodology, hereafter clonogenic HTS, exhibits excellent robustness (Z values >0.5) and shows high reproducibility (>95%). We propose that clonogenic HTS we developed can function as a drug discovery platform to identify compounds that inhibit tumor regrowth following radiation therapy, to identify new efficacious pair-wise combinations of known oncologic therapies, or to identify novel modulators of approved therapies.

cancer biology↗

bioRxiv2020

An MRI protocol for anatomical and functional evaluation of the California sea lion brain

We describe a research MRI protocol for in vivo evaluation of pinniped brains using standard human clinical MRI hardware and pulse sequences. Our intended application is to study development of California sea lions (Zalophus californianus) exposed in utero to domoic acid (DOM) produced by harmful algae blooms in the coastal Pacific Ocean. In cases where the fetus survives to birth, exposure to the toxin in utero could result in developmental abnormalities leading to neurological and behavioral deficits. Prior studies on sea lions naturally exposed to DOM as adults have demonstrated hippocampal atrophy and altered mesial temporal connectivity. This MRI protocol is therefore intended to depict the hippocampal formation as the primary region of interest, and to provide longitudinal measures of brain functional and structural connectivity as well as quantitative anatomical evaluations. Scan quality and utility are assessed by comparison with prior studies in live and post mortem sea lion brains. We include the first determination of cerebral blood flow mapping using MRI, and also the first fiber tractography using diffusion-weighted imaging from a live sea lion brain. The protocol also facilitates screening for common neurological pathologies, including tumors, trauma and hemorrhages. We believe the protocol would be suitable for any pinniped that can fit inside a human MRI scanner.

neuroscience↗