Biology subjects

Edlow, B.

Publications and source records attributed to Edlow, B..

5 recordsLinked to original sources

bioRxiv2026

The Infant Brainstem - A Multimodal Multiscale Postmortem Imaging Pipeline

Brainstem disorders in human infants - including sudden infant death syndrome (SIDS), the leading cause of postnatal infant mortality in the United States - are characterized by cellular and molecular abnormalities that conventional neuroimaging cannot detect. A substantial challenge arises from the fact that the immature myelination of the infant brain severely degrades MRI contrast, leaving the discrete nuclei and white matter tracts of the brainstem poorly resolved at the scale where pathology occurs. We introduce a postmortem imaging pipeline that bridges this gap by integrating four spatially registered modalities: whole-brain magnetic resonance imaging (MRI) (550 m), brainstem-specific MRI (150 m), polarization-sensitive optical coherence tomography (PSOCT, 10 m), and histology with immunohistochemistry (1.88 m). Our central finding is that PSOCT provides excellent tissue contrast independent of myelination state - directly overcoming the principal limitation of MRI in the infant brain -while enabling three-dimensional visualization of nuclei and tracts at resolutions 15 to 55 times finer than MRI alone. Histology provides cellular-level ground truth and validates the optical contrasts. Applied here to a normative 34-day-old infant brainstem, this pipeline establishes a generalizable framework for studying infant brainstem neuroanatomy in three dimensions, with particular relevance to disorders such as SIDS where gross anatomy is intact but cellular abnormalities remain the target of investigation.

neuroscience↗

bioRxiv2026

A hypothalamic-brainstem activity sequence underlies arousal fluctuations during daytime drowsiness

During monotonous tasks, struggling with drowsiness leads to dynamic fluctuations in vigilance and task performance. Whether these moment-to-moment fluctuations are regulated by sleep-wake control circuitry remains unknown. Here, we used high-resolution 7T fMRI optimized for subcortical imaging to resolve activity across the human arousal regulatory system, including the hypothalamus, brainstem nuclei, basal forebrain, and thalamus, during a sustained attention task as subjects spontaneously experienced drowsiness. We identified a coordinated activity pattern locked to behavioral failures: widespread transient suppression during arousal drops and reactivation during recovery across all arousal-promoting regions, with opposite responses in the sleep-promoting hypothalamic preoptic area. These changes unfolded over [~]10-15 s in a 30 consistent sequence, led by the hypothalamic nuclei. Furthermore, suppression of brainstem nuclei preceded cortical infraslow (<0.05 Hz) oscillations, implicating a role in global neurovascular dynamics. These findings provide a temporally resolved, network-level portrait of human subcortical dynamics during drowsiness and identify a hypothalamic-led, brainstem-mediated activity sequence underlying behavioral arousal fluctuations and global cortical hemodynamics.

neuroscience↗

bioRxiv2025

Visualizing Effective Connectivity in the Human Brain

To enhance mechanistic understanding of effective connectivity in the human brain, we created a tool that links high-temporal resolution transcranial magnetic stimulation electroencephalography (TMS-EEG) with high-spatial resolution diffusion MRI. This tool, Surface to Tractography Real-time EEG Activation Mapping in 4 Dimensions (STREAM-4D), integrates electrophysiologic source estimation models from TMS-evoked potentials (TEPs) with structural connectivity models from diffusion MRI tractography. In a proof-of-principle application, we used STREAM-4D to analyze TMS-EEG and diffusion MRI tractography data in a neurotypical subject across three stimulation sites: premotor, parietal, and occipital cortex. STREAM-4D revealed extensive structural connections associated with the TMS-evoked source models, involving thalamocortical, ipsilateral cortico-cortical, and transcallosal cortico-cortical connections. Activity-weighted structural connectivity differed for the three stimulation sites but shared two extensively connected nodes: the ipsilateral thalamus and putamen. STREAM-4D provides opportunities to elucidate how electrical activity evoked by a TMS pulse is related to underlying white matter architecture.

neuroscience↗

bioRxiv2024

Shared subcortical arousal systems across sensory modalities during transient modulation of attention

Subcortical arousal systems are known to play a key role in controlling sustained changes in attention and conscious awareness. Recent studies indicate that these systems have a major influence on short-term dynamic modulation of visual attention, but their role across sensory modalities is not fully understood. In this study, we investigated shared subcortical arousal systems across sensory modalities during transient changes in attention using block and event-related fMRI paradigms. We analyzed massive publicly available fMRI datasets collected while 1,561 participants performed visual, auditory, tactile, and taste perception tasks. Our analyses revealed a shared circuit of subcortical arousal systems exhibiting early transient increases in activity in midbrain reticular formation and central thalamus across perceptual modalities, as well as less consistent increases in pons, hypothalamus, basal forebrain, and basal ganglia. Identifying these networks is critical for understanding mechanisms of normal attention and consciousness and may help facilitate subcortical targeting for therapeutic neuromodulation.

neuroscience↗

bioRxiv2023

Eddy current-induced artifacts correction in high gradient strength diffusion MRI with dynamic field monitoring: demonstration in ex vivo human brain imaging

PurposeTo demonstrate the advantages of spatiotemporal magnetic field monitoring to correct eddy current-induced artifacts (ghosting and geometric distortions) in high gradient strength diffusion MRI (dMRI). MethodsA dynamic field camera with 16 NMR field probes was used to characterize eddy current fields induced from diffusion gradients for different gradients strengths (up to 300 mT/m), diffusion directions, and shots in a 3D multi-shot EPI sequence on a 3T Connectom scanner. The efficacy of dynamic field monitoring-based image reconstruction was demonstrated on high-resolution whole brain ex vivo dMRI. A 3D multi-shot image reconstruction framework was informed with the actual nonlinear phase evolution measured with the dynamic field camera, thereby accounting for high-order eddy currents fields on top of the image encoding gradients in the image formation model. ResultsEddy current fields from diffusion gradients at high gradient strength in a 3T Connectom scanner are highly nonlinear in space and time, inducing high-order spatial phase modulations between odd/even echoes and shots that are not static during the readout. Superior reduction of ghosting and geometric distortion was achieved with dynamic field monitoring compared to ghosting approaches such as navigator- and structured low-rank-based methods or MUSE, followed by image-based distortion correction with eddy. Improved dMRI analysis is demonstrated with diffusion tensor imaging and high-angular resolution diffusion imaging. ConclusionStrong eddy current artifacts characteristic of high gradient strength dMRI can be well corrected with dynamic field monitoring-based image reconstruction, unlike the two-step approach consisting of ghosting correction followed by geometric distortion reduction with eddy.

bioengineering↗