Biology subjects

Butts Pauly, K.

Publications and source records attributed to Butts Pauly, K..

6 recordsLinked to original sources

bioRxiv2026

Dose-dependent ultrasound neuromodulation of the human brain

Transcranial ultrasound stimulation (TUS) can noninvasively modulate deep brain structures, but the relationship between delivered dose and neuromodulatory response remains poorly characterized in humans. Here, we show that ultrasound-induced tissue displacement measured in vivo predicts local and downstream functional neuromodulation. In 24 healthy adults, we combined magnetic resonance acoustic radiation force imaging (MR-ARFI) with concurrent TUS-fMRI in a double-blind, counterbalanced, within-subject design. Relative to active control stimulation, targeting the lateral geniculate nucleus (LGN) increased visually evoked BOLD responses in the LGN and ipsilateral primary visual cortex, localized to the retinotopic projection zone of the stimulated LGN site. Displacement predicted effect magnitude in both regions across participants and covaried with voxelwise responses within participants. Simulated in situ intensity showed no significant association with displacement or neuromodulatory response. These findings link in vivo mechanical displacement to functional modulation of a human thalamocortical circuit, providing an empirical basis for individualized dosing in causal neuroscience and clinical intervention.

neuroscience↗

bioRxiv2026

Psychophysical validation of calibrated white-noise and tuned-noise auditory masks for transcranial focused ultrasound

Auditory confounds have proven to be a major hurdle in the elucidation of veridical neuromodulation effects with transcranial ultrasound stimulation (TUS). Auditory noise masks are an essential method to reduce the audibility of TUS and have shown promise in several studies. Here we describe a novel approach for design, calibration, and psychometric validation of auditory noise masks to reduce the perceptibility of TUS. White noise masks and spectrum-tuned masks matched to a TUS protocol that generates highly salient auditory costimulation (487.5 Hz pulse repetition frequency, 10% duty cycle, 68 W/cm2 pulse-peak average intensity, 500 kHz acoustic frequency) were generated, and dB(A) levels were calibrated with an artificial ear. The masker levels needed to reduce TUS detection performance in a two-interval forced choice task were determined with an adaptive QUEST+ staircase in 20 neurotypical participants. Detection performance of this highly salient TUS protocol was driven to near chance performance (<55%) in 17/20 participants with white-noise and 18/20 participants with spectrum-tuned noise. However, high masker levels approaching safety limits were needed to render TUS inaudible for the majority of participants, indicating the need for formal masker calibration for these TUS settings. Additionally, against expectation the spectrum-tuned masker did not significantly outperform the white-noise masker, suggesting that perceptibility of TUS auditory costimulation does not lawfully follow the sound expected from its pulse envelope and the known spectrum of human hearing.

neuroscience↗

bioRxiv2026

Effects of transcranial focused ultrasound stimulation to human lateral geniculate nucleus on visual perception and steady-state visual evoked potentials

Transcranial ultrasound stimulation (TUS) is an emerging tool to non-invasively modulate neural activity in deep brain areas. A key need in accelerating TUS into cognitive neuroscience and neuropsychiatry is to better understand how different sonication parameters relate to neuromodulatory effects. Here we assess the role of pulse repetition frequency (PRF), a key TUS parameter thought to determine the relative contribution of molecular displacement and acoustic radiation force effects on neural tissue using the human subcortical visual pathway as a testbed. We combined frequency-tagged steady-state visual evoked potential (SSVEP) measures of contrast-response with contrast increment detection psychophysics as neural and behavioral readouts of visual pathway function. We used structural MRIs and acoustic simulations to target the lateral geniculate nucleus (LGN). Concurrent with visual stimulus presentation, the left LGN or a more superficial control site were stimulated with a neuronavigated depth-steerable 4-element TUS transducer at a range of PRFs with 68 W/cm2 free-water ISPPA, and a 10% duty cycle. An effective white-noise auditory mask blinded participants to stimulation conditions. Recordings from 25 neurotypical participants failed to detect any impact of TUS on SSVEP response amplitude, SSVEP response latency, or perceptual behavior. Analysis of simulations generated from the measured transducer positions grant reasonably high confidence that the LGN was within the TUS focus in most participants, with no correlation between targeting accuracy and changes in activity during TUS. Our results provide a cautionary note about the effect size of neuronavigated TUS for online causal manipulations in cognitive and clinical neuroscience.

neuroscience↗

bioRxiv2025

Parameter optimisation for mitigating somatosensory confounds during transcranial ultrasonic stimulation

Transcranial ultrasonic stimulation (TUS) redefines what is possible with non-invasive neuromodulation by oaering unparalleled spatial precision and flexible targeting capabilities. However, peripheral confounds pose a significant challenge to reliably implementing this technology. While auditory confounds during TUS have been studied extensively, the somatosensory confound has been overlooked thus far. It will become increasingly vital to quantify and manage this confound as the field shifts towards higher doses, more compact stimulation devices, and more frequent stimulation through the temple where co-stimulation is more pronounced. Here, we provide a systematic characterisation of somatosensory co-stimulation during TUS. We also identify the conditions under which this confound can be mitigated most eaectively by mapping the confound-parameter space. Specifically, we investigate dose-response eaects, pulse shaping characteristics, and transducer-specific parameters. We demonstrate that somatosensory confounds can be mitigated by avoiding near-field intensity peaks in the scalp, spreading energy across a greater area of the scalp, ramping the pulse envelope, and delivering equivalent doses via longer, lower-intensity pulses rather than shorter, higher-intensity pulses. Additionally, higher pulse repetition frequencies and fundamental frequencies reduce somatosensory eaects. Through our systematic mapping of the parameter space, we also find preliminary evidence that particle displacement (strain) may be a primary biophysical driving force behind peripheral somatosensory co-stimulation. This study provides actionable strategies to minimise somatosensory confounds, which will support the thorough experimental control required to unlock the full potential of TUS for scientific research and clinical interventions. Highlights- Tactile, thermal, and even painful somatosensory confounds may occur during TUS. - Confounds can be mitigated via pulse shaping & transducer-specific parameters. - Valid and replicable TUS research requires control for peripheral confounds. - Particle displacement may be a primary driving force for somatosensory confounds.

neuroscience↗

bioRxiv2019

Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep

BackgroundNeuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI).\n\nObjectiveTo investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI.\n\nMethodsTwo rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS.\n\nResultsNo FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS.\n\nConclusionsThe absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.

bioengineering↗

bioRxiv2018

Elimination of peripheral auditory pathway activation does not affect motor responses from ultrasound neuromodulation

Recent studies in a variety of animal models including rodents, monkeys, and humans suggest that transcranial focused ultrasound (tFUS) has considerable promise for non-invasively modulating neural activity with the ability to target deep brain structures. However, concerns have been raised that motor responses evoked by tFUS may be due to indirect activation of the auditory pathway rather than direct activation of motor circuits. In this study, tFUS-induced electromyography (EMG) signals were recorded and analyzed in wild-type (WT) normal hearing mice and two strains of genetically deaf mice to examine the involvement of the peripheral auditory system in tFUS-stimulated motor responses. In addition, auditory brainstem responses (ABRs) were measured to elucidate the effect of the tFUS stimulus envelope on auditory and motor responses. We also varied the tFUS stimulation duration to measure its effect on motor response duration. We show, first, that the sharp edges in a tFUS rectangular envelope stimulus activate the peripheral afferent auditory pathway and, second, that smoothing these edges eliminates the auditory responses without affecting the motor responses in normal hearing WT mice. We further show that by eliminating peripheral auditory activity using two different strains of deaf knockout mice, motor responses are the same as in normal hearing WT mice. Finally, we demonstrate a high correlation between tFUS pulse duration and EMG response duration. These results support the concept that tFUS-evoked motor responses are not a result of stimulation of the peripheral auditory system.

neuroscience↗