Biology subjects

Strom, A.

Publications and source records attributed to Strom, A..

5 recordsLinked to original sources

bioRxiv2026

Spontaneous Hemodynamic Oscillations during Sleep Coordinate Directional CSF Flow in the Subarachnoid Space and Ventricles

During sleep, cerebrospinal fluid (CSF) flow is enhanced and thought to facilitate clearance of metabolic waste from the brain. Human imaging has shown that sleep is associated with large waves of bulk CSF flow in the fourth ventricle; however, the CSF flow dynamics around brain tissue are unknown. Here, we investigated how CSF flow is organized across the subarachnoid space, a key site both for fluid exchange across cortical surface and for transport out of the cranium. We used an MRI technology at 7 Tesla that simultaneously measures cortical hemodynamics and slow subarachnoid CSF flow and applied this during sleep. We found that spontaneous infraslow hemodynamic oscillations were coupled to spatially structured, directional CSF flow throughout both ventricular and subarachnoid compartments. Hemodynamic oscillations and fourth-ventricle bulk flow were both associated with brain-wide CSF flow at different phases, indicating that they reflect a single coordinated CSF movement cycle. Compared to cardiac pulsations, a canonical driver of CSF movement, hemodynamic-driven CSF flow showed a distinct directional pattern and was smaller in instantaneous amplitude but produced substantially greater cumulative displacement and thus greater potential for transport within an oscillation period. Together, these findings show that hemodynamic oscillations during sleep are coupled to temporally coordinated and directional CSF flow throughout the ventricles and subarachnoid space, suggesting that sleep-dependent neuronal activity drives fluid movement across the human brain in a distinct spatial pattern.

neuroscience↗

bioRxiv2026

Quantification of cardiac-locked brainstem velocity at high resolution based on retrospectively-gated DENSE MRI at 7T

PurposeThe motion of the brain tissue within the skull is thought to be induced by cardiac pulsations and other hemodynamic processes and may influence CSF flow, but its precise drivers and downstream effects are unclear. Understanding these phenomena requires an accurate and precise method of tissue motion quantification that can be extended to investigate multiple potential drivers of tissue motion in vivo. MethodsHere, a version of the Displacement ENcoding with Stimulated Echoes (DENSE) pulse sequence was implemented to measure cardiac-locked velocity responses in the pons and midbrain in eight healthy volunteers. The method featured retrospective cardiac gating, a single mixing time, and measured multiple voxel sizes. ResultsA previously undescribed double-peak pattern of cardiac-locked longitudinally directed brainstem velocity was identified that appears to reflect both nonrigid and rigid motion components. This pattern was only visible when estimating the cardiac response using absolute time after systole instead of the percentage of the cardiac cycle. Measurements were performed in a custom-built slow-flow phantom, and repeat sessions were acquired in two volunteers to assess accuracy and precision. Despite potential increased influence of CSF motion with larger voxel sizes, no voxel-size-dependent bias was found in the velocity estimations. Lack of voxel size bias was attributed to the complexities of partial-volume effects between CSF and tissue in phase-valued data that were evaluated using numerical simulations. ConclusionIn sum, a method to measure brain tissue motion with high spatiotemporal precision is presented that can be extended to applications beyond measuring cardiac-locked motion.

neuroscience↗

bioRxiv2025

Quantifying brain-wide cerebrospinal fluid flow dynamics using slow-flow-sensitized phase-contrast MRI

Cerebrospinal fluid (CSF) flow is a key component of the brains waste clearance system. However, our understanding of CSF flow in the human brain, particularly within the brain-wide subarachnoid space (SAS), is limited due to a lack of non-invasive tools for measuring slow flow. Here, we propose a CSF flowmetry technique using phase-contrast MRI combined with a slow-flow-sensitized acquisition. It achieves high sensitivity in measuring slow CSF flow (e.g., 100 m/s), and enables quantitative measurement of the velocity and direction with whole-brain coverage, spanning from ventricles to SAS. Our proof-of-concept results demonstrate repeatable flow measurements and show that cardiac pulsation induces coherent CSF flow changes within the SAS. Our data also suggest that cardiac pulsation has a stronger driving effect on brain-wide CSF flow compared to respiration. This technique provides a valuable tool for investigating CSF dynamics and pathways to advance a holistic understanding of brain-wide CSF flow. TeaserA novel MR technique enables noninvasive, quantitative mapping of slow cerebrospinal fluid flow in the subarachnoid space across the human brain.

bioengineering↗

bioRxiv2024

Dimerization-dependent gel-like condensation with dsDNA underpins the activation of human cGAS

Cyclic G/AMP Synthase (cGAS) initiates inflammatory responses against pathogenic double-stranded (ds)DNA. Although it is well established that cGAS forms phase-separated condensates with dsDNA, their function remains poorly defined. We report here that the dimerization of cGAS on dsDNA creates a mesh-like network, leading to gel-like condensate formation. Although cGAS binds to and forms condensates with various nucleic acids, only dsDNA permits the dimerization necessary for activation and gelation. cGAS co-condenses dsDNA and other nucleic acids but retains a distinct dsDNA-mediated gel-like substate, which single-stranded RNA can dissolve and deactivate the enzyme. Moreover, gel-like, but not liquid-like, condensation not only protects bound dsDNA from exonucleases, but also limits the mobility of NTPs and the dinucleotide intermediate for efficient cGAMP synthesis. Together, our results show that enzymes can finetune surrounding microenvironments to regulate their signaling activities.

biochemistry↗

bioRxiv2022

Altered excitatory and inhibitory neuronal subpopulation parameters are distinctly associated with tau and amyloid in Alzheimer's disease

BackgroundNeuronal and circuit level abnormalities of excitation and inhibition are shown to be associated with tau and amyloid-beta (A{beta}) in preclinical models of Alzheimers disease (AD). These relationships remain poorly understood in patients with AD. MethodsUsing empirical spectra from magnetoencephalography (MEG) and computational modeling (neural mass model; NMM) we examined excitatory and inhibitory parameters of neuronal subpopulations and investigated their specific associations to regional tau and A{beta}, measured by positron emission tomography (PET), in patients with AD. ResultsPatients with AD showed abnormal excitatory and inhibitory time-constants and neural gains compared to age-matched controls. Increased excitatory time-constants distinctly correlated with higher tau depositions while increased inhibitory time-constants distinctly correlated with higher A{beta} depositions. ConclusionsOur results provide critical insights about potential mechanistic links between abnormal neural oscillations and cellular correlates of impaired excitatory and inhibitory synaptic functions associated with tau and A{beta} in patients with AD. FundingThis study was supported by the National Institutes of Health grants: K08AG058749 (KGR), F32AG050434-01A1 (KGR), K23 AG038357 (KAV), P50 AG023501, P01 AG19724 (BLM), P50-AG023501 (BLM & GDR), R01 AG045611 (GDR); AG034570, AG062542 (WJ); NS100440 (SSN), DC176960 (SSN), DC017091 (SSN), AG062196 (SSN); a grant from John Douglas French Alzheimers Foundation (KAV); grants from Larry L. Hillblom Foundation: 2015-A-034-FEL and (KGR); 2019-A-013-SUP (KGR); a grant from the Alzheimers Association: (PCTRB-13-288476) (KAV), and made possible by Part the CloudTM, (ETAC-09-133596); a grant from Tau Consortium (GDR & WJJ), and a gift from the S. D. Bechtel Jr. Foundation.

neuroscience↗