Biology subjects

Mohammadjavadi, M.

Publications and source records attributed to Mohammadjavadi, M..

8 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

MR-ARFI and Beyond: Characterizing the Temporal Dynamics of Acoustic Radiation Force in Human Brain

Purpose: Magnetic Resonance Acoustic Radiation Force Imaging (MR-ARFI) encodes focused ultrasound (FUS)-induced tissue displacements to MR phase shifts. Because these phase shifts are small, optimizing displacement sensitivity and minimizing motion artifacts requires characterization of the temporal dynamics of acoustic radiation force (ARF). Beyond sequence design, such characterization enables MR-ARFI to serve as a probe of brain viscoelastic behavior and can inform the design of therapeutic ultrasound pulsing schemes by quantifying how rapidly tissue deforms and relaxes. Methods: We developed a dynamic model assuming a gamma-variate impulse response for ARF(t), with time constant ({tau}) to be estimated. A single-shot spin echo ARFI acquisition with a bipolar motion encoding gradient (MEG) was implemented, incorporating retrospective corrections for head motion and physiological noise. A 500 kHz FUS pulse was applied in on/off blocks while systematically varying the timing between the MEG and sonication. The resulting phase time series were fit to the model to estimate time constant in five human participants. To assess sensitivity to tissue stiffness, {tau} was additionally measured in two customized gelatin phantoms of differing stiffness, characterized independently by MR elastography (MRE). Results: The average measured time constant in human participants was {tau} 3.7 {+/-} 0.27 ms. Comparing the two phantoms, the stiffer phantom exhibited a shorter {tau} (3.0-3.5 ms) than the softer phantom (4.0-4.5 ms), which tracked the MRE-derived Kelvin-Voigt viscoelastic time constants. In addition, the peak ARFI displacement was lower in the stiffer phantom (0.17 vs 0.74 m for the less stiff phantom), and a broader displacement focal spot size (FWHM 22 mm vs 15 mm). Conclusion: This time series approach with motion and physiological noise corrections validates an MR-based technique capable of characterizing the brain's temporal response to sonication-induced mechanical forces, providing a foundation for optimizing the design of ultrasound pulsing schemes for ARFI, as well as for future studies of brain biomechanics.

bioengineering↗

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↗

bioRxiv2026

Noninvasive Diagnostic Ultrasound-Guided Focused Ultrasound Enables Selective, Reversible Inhibition of Peripheral Nociceptive Fibers and Prevents Acute Pain

BackgroundAcute postoperative pain remains a major clinical therapeutic challenge. Current peripheral nerve blockade (PNB) techniques are effective for some patients but are limited by invasiveness, short duration, reliance on highly trained providers, and off-target motor and sensory effects. Focused ultrasound (FUS) is a novel neuromodulatory technology with the potential to achieve noninvasive, selective, reversible, and prolonged inhibition of peripheral nociceptive fibers to prevent and treat acute pain. We hypothesized that noninvasive transcutaneous targeting of the rat sciatic nerve using co-aligned diagnostic ultrasound (dUS) and FUS transducers could produce selective and reversible inhibition of nociceptive pain behaviors while preserving motor and non-nociceptive sensory functions. MethodsIn an in vivo rat hindpaw incisional (HPI) pain model, using a novel, transcutaneous dUS-guided FUS system, the sciatic nerve was located with dUS, and FUS energy was applied to it just prior to hindpaw incision. FUS parameters were iteratively adjusted to achieve reversible, selective inhibition of nociceptive behaviors without changing motor and non-pain sensory behaviors. Animals were randomized into six groups: No Intervention (Control), HPI Only (Disease Control), Sham FUS, FUS Only, FUS+HPI (Intervention), and LA+HPI (Positive Control). Primary outcomes were changes in nociceptive sensory functions, assessed by thermal and mechanical sensitivity. Secondary outcomes were changes in non-nociceptive sensory and motor functions, assessed by hindpaw flexion and extension reflexes. ResultsCompared with the HPI Only group, the FUS+HPI group demonstrated (1) significant attenuation of hindpaw thermal hypersensitivity from day 0 - week 5.0 and week 8.0 - 16.0 (p < 0.05-0.001); (2) significant attenuation of mechanical hypersensitivity from day 0 until week 4.0 (p < 0.05-0.001); (3) no significant attenuation of flexion; and (4) no significant attenuation of extension. ConclusionsTranscutaneous dUS-guided FUS enables selective, reversible inhibition of A{delta} and C nociceptive fiber mediated behaviors while sparing A motor and A{beta} sensory behaviors. FUS-induced PNB prevented both acute and persistent pain behaviors. These findings support FUS as a promising noninvasive peripheral nerve blockade strategy for acute pain management.

neuroscience↗

bioRxiv2024

Optimization of MR-ARFI for Human Transcranial Focused Ultrasound

Magnetic resonance acoustic radiation force imaging (MR-ARFI) is an exceptionally promising technique to non-invasively confirm targeting accuracy and estimate exposure of low-intensity transcranial focused ultrasound stimulation. MR-ARFI uses magnetic field motion encoding gradients to visualize the MR phase changes generated by microscopic displacements at the ultrasound focus. Implementing MR-ARFI in the human central nervous system has been hindered by 1) phase distortion caused by subject motion, and 2) insufficient signal-to-noise ratio at low (<1.0 MPa) ultrasound pressures. The purpose of this study was to optimize human MR-ARFI to allow reduced ultrasound exposure while at the same time being robust to bulk and physiological motion. We demonstrate that a time series of single-shot spiral acquisitions, while triggering ultrasound on and off in blocks, provides ARFI maps that with correction are largely immune to bulk and pulsatile brain motion. Furthermore, the time series approach allows for a reduction in ultrasound exposure per slice while improving motion robustness with reduced scan time. The focused ultrasound beam can be visualized in an 80 second scan with our protocol, enabling iteration for image-guided targeting. We demonstrated robust ARFI signals at the expected target in 4 participants. Our results provide persuasive proof-of-principle that MR-ARFI can be used as a tool to guide ultrasound-based precision neural circuit therapeutics.

biophysics↗

bioRxiv2021

Transcranial Focused Ultrasound Neuromodulation of the Thalamic Visual Pathway in a Large Animal Model

BackgroundNeuromodulation of deep brain structures via transcranial ultrasound stimulation (TUS) is a promising, but still elusive approach to non-invasive treatment of brain disorders. ObjectiveThe purpose of this study was to determine whether MR-guided TUS of the lateral geniculate nucleus (LGN) can modulate visual evoked potentials (VEPs) and cortical brain oscillations in a large animal model. MethodsThe lateral geniculate nucleus (LGN) on one side was identified with T2-weighted MRI in sheep (all male, n=9). MR acoustic radiation force imaging (MR-ARFI) was used to confirm a tight sonication focus. Electroencephalographic (EEG) signals were recorded, and the visual evoked potential (VEP) peak-to-peak amplitude (N70 and P100) was calculated for each trial. Time-frequency spectral analysis was performed to elucidate the effect of TUS on cortical brain dynamics. ResultsThe VEP peak-to-peak amplitude was reversibly suppressed relative to baseline during TUS. Dynamic spectral analysis demonstrated a change in cortical oscillations when TUS is paired with visual sensory input, but not when TUS is applied by itself. ConclusionTUS non-invasively delivered to LGN can neuromodulate visual activity and oscillatory dynamics in large mammalian brains.

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↗