bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.10.23.760846

A preclinical platform for focused ultrasound delivery from microplate to awake brain

Bell, M. S.·Williams, M. J.·Walton, C. M.·Hughes, B. W.·Roddey, T. S.·Oldham, B. B.·Bruno, C. E.·Peterson, K. D.·Kendrick, B. J.·Caiello, B. P.·Miller, B. A.·Rowland, N. C.·Sahin, O.·Strickland, B. A.
View original source ↗Export metadata ↓

Abstract

Background. Focused ultrasound (FUS) has broad therapeutic potential, but its mechanisms of action are poorly understood. Preclinical FUS research enables rigorous interrogation of understudied parameters, but fragmented, single-purpose benchtop devices prevent standardized acoustic exposure across models. Objective. To describe a unified preclinical FUS platform for cell culture, ex vivo tissue, and awake stereotaxic in vivo delivery in one lightweight system, validated using glioblastoma as a disease model. Methods. We performed single-well FUS delivery to 96-well microplates, single-well delivery to freshly resected human glioblastoma tissue, and stereotaxic transcranial delivery to awake, head-fixed mice ambulating freely on a floating cage. Output was independently calibrated in free field, with measured microplate insertion loss. Pulsed low-intensity focused ultrasound (pLIFU) was applied to GL261-bearing mice, resected human glioblastoma, and macrophage cell lines. Results. Awake stereotaxic pLIFU produced acute tumor signal attenuation in GL261-bearing mice (mean log2 fold-change -1.66 versus +5.20 controls, p = 0.016) with bioluminescence evidence consistent with focal targeting. Ex vivo pLIFU produced directionally consistent immunophenotypic shifts in human glioblastoma (increased iNOS+, decreased Arg1+ populations). In vitro, pLIFU reduced CD80 on immunosuppressive macrophages to 73% of baseline in RAW 264.7 cells (p = 0.0008, n = 5) and 64% in THP-1 cells (p = 0.0006, n = 2), with MHC II upregulation in RAW 264.7 (ratio 1.65, p = 0.004) and ARG1 reduction in THP-1 (ratio 0.52, p = 0.0025). Conclusions. A unified preclinical FUS platform validated across in vitro, ex vivo, and awake in vivo applications enables stereotaxically guided transcranial FUS in awake, head-fixed mice ambulating in an exploratory manner during sonication, and single-well microplate treatments.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Bell, M. S., Williams, M. J., Walton, C. M., Hughes, B. W., Roddey, T. S., Oldham, B. B., Bruno, C. E., Peterson, K. D., Kendrick, B. J., Caiello, B. P., Miller, B. A., Rowland, N. C., Sahin, O., Strickland, B. A.. 2026-10-29. A preclinical platform for focused ultrasound delivery from microplate to awake brain. https://doi.org/10.64898/2026.10.23.760846

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Rapid switching of in-phase and anti-phase interhemispheric rhythms within a single theta cycle: a mechanistic explanation

The granular retrosplenial cortex (RSG) supports memory consolidation and spatial navigation. In vivo recordings of local field potential (LFP) from RSG reveal coexisting gamma (30-80 Hz) and spline (100-160 Hz) oscillations, coupled to distinct phases of the background theta ([~]8 Hz) rhythm. Remarkably, bilateral recordings reveal that gamma and splines exhibit divergent interhemispheric phase relationships: gamma is in-phase across hemispheres, while splines are anti-phase. Here, using numerical bifurcation analysis of next-generation neural mass models, we show that RSG oscillations within a single hemisphere can be understood as alternation of PING (pyramidal-interneuron gamma) and ING (interneuron gamma) mechanisms in an excitatory-inhibitory network. Theta-frequency external drive to the inhibitory population switches the network between these two rhythms. Next, we build canonical interhemispheric circuits, composed of two such excitatory-inhibitory modules, delay-coupled across hemispheres. These circuits switch between in-phase gamma and anti-phase splines within a single theta cycle, reproducing the cross-spectral statistics of experimental RSG recordings. Finally, we present analytical results for threshold-linear neural mass models, showing cross-hemispheric phase patterning is governed by the ratio of cross-hemispheric delay to local inhibitory delay; we obtain explicit ranges of this ratio for which RSG-like patterning could be expected. Our work establishes that the unique oscillatory profile of RSG can be explained parsimoniously by minimal interhemispheric circuit configurations and provides a framework for experimental interrogation of interhemispheric rhythms.

neuroscience↗
bioRxiv2026

Brain representations of visual short-term memories during healthy human aging: occipital decline and frontoparietal compensation

Visual short-term memory declines steeply with age, but the link to neural representations of memory content remains unknown. We used fMRI decoding to relate remembered motion-direction representations in visual and frontoparietal cortex to age and performance, in 115 adults, aged 25-87, from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) cohort. Decoding was strongest in visual cortex, but also significant in frontoparietal regions, with different profiles. Visual representations weakened with memory load and age, and statistically mediated age-related performance decline, especially during recall. This coupling, however, weakened with age: some older adults retained stronger visual representations than performance implied, suggesting impaired access to a partially preserved memory trace. Frontoparietal representations, instead, were largely insensitive to load and strengthened with age during maintenance, partially offsetting performance decline. Therefore, interventions to boost VSTM in older adults might target compensatory frontoparietal representations during memory maintenance, and readout of untapped visual representations at recall.

neuroscience↗
bioRxiv2026

Lexical surprisal drives pupil dilation during continuous story listening

The pupil famously adjusts its dilation in response to light, but its role extends far beyond this basic sensory function. Its fluctuations index arousal and mental effort, beyond luminance-related dynamics, making it a sensitive marker of internal cognitive states. A growing body of work shows that these pupil-linked signals extend beyond the visual domain. However, which processes drive pupil responses in more naturalistic settings remains unclear as most evidence comes from tightly controlled paradigms that strip away the richness of real-world experience. Language offers a uniquely powerful window into this question, as it can allow us to create rich paradigms without having any visual, i.e. luminance, confounds. Moreover, language comprehension hinges on continuous prediction: listeners constantly generate expectations about upcoming input, and the discrepancy between expectation and actual input - contextual prediction error, or surprisal - carries measurable cognitive costs. Here, we tested the hypothesis that pupil-linked arousal indexes these linguistic surprisal signals during naturalistic listening. We recorded pupil responses while volunteers listened to naturalistic spoken stories in darkness, which were either intact or reversed. Reversed speech preserves the acoustics of the signal while destroying its intelligibility. Pupil dilation selectively tracked lexical surprisal within a late window of 1,700 to 2,350 milliseconds following word onset, in forward, but not control, backward speech. These findings indicate that pupil-linked arousal is tuned to global, context-dependent processing, tracking the cognitive cost of updating a predictive model during naturalistic listening.

neuroscience↗