Name: A Methodological Protocol and Considerations for Transcranial Ultrasonic Stimulation in Exploratory Clinical Human Studies (Video) | JoVE Journal
Uploaded: 2025-12-12T13:40:00.000+00:00
Duration: 9 min 47 s
Description: Learn transcranial ultrasonic stimulation for non-invasive neuromodulation in stroke recovery. This protocol establishes safety measures and standardized procedures for enhancing motor cortex excitability in patients.

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This project was supported by the American Heart Association Innovative Project Award and Collaborative Science Award (W.F. 20IPA353600039 and 25CSA1417550) and the Duke Gilhuly award (S.S.).&#160;The video component was made possible by the altruistic help from Ms. Yu Chu and Mr. Jingting Li.

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<li>Aubry, J. F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((ITRUSST+consensus+on+biophysical+safety+for+transcranial+ultrasonic+stimulation%5BTitle%5D)+AND+%22arXiv%22%5BJournal%5D)">ITRUSST consensus on biophysical safety for transcranial ultrasonic stimulation.</a> arXiv. , https://ui.adsabs.harvard.edu/abs/2023arXiv231105359A (2023).</li>
<li>Osada, T., Konishi, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Noninvasive+intervention+by+transcranial+ultrasound+stimulation%3A+modulation+of+neural+circuits+and+its+clinical+perspectives%5BTitle%5D)+AND+%22Psychiatry+Clin+Neurosci%22%5BJournal%5D)">Noninvasive intervention by transcranial ultrasound stimulation: modulation of neural circuits and its clinical perspectives.</a> Psychiatry Clin Neurosci. 78 (5), 273-281 (2024).</li>
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</ol>

Wuwei Feng &#38; Xiaoning Jiang have an ultrasound stimulation-related patent filed with the United States Patent and Trademark Office (PCT/US2025/041316).

There has been significant research enthusiasm for the application of TUS in neurological conditions; however, a need exists for increased scientific rigor and replication of results. A successful TUS on the intended target tissue relies on several critical steps. First, the transmitting sensitivity of the transducer needs to be correctly characterized. Options include following Step 2 of this protocol, outsourcing to a collaborator, and utilizing vendor's service. The second critical step is targeting, i.e., determining...

A unique and desirable combination, the deep, focal, and non-invasive nature of transcranial ultrasonic stimulation1 (TUS) has spurred growing interests in exploring its therapeutic potentials for neurological and neuropsychiatric diseases (e.g., stroke2, Parkinson's disease3, depression4, Alzheimer's disease5, etc.). Expert consensus and guidelines have sought to improve the reproducibility and interpretability of TUS research6,7. However, these primarily address the broader basic research applications of TUS and offer less guidance on exploring therapeutic relevance in humans. For example, when comparing basic and clinical TUS research, the total stimulation duration (TSD) differs substantially - often up to around 80 s in basic research8,9 versus over 10 min in exploratory protocols designed to approximate clinical use2. Such distinctions underscore the need for tailored guidance when exploratorily applying TUS to a neurologically diseased cohort. While this protocol focuses on TUS in stroke, its framework is broadly applicable to other patient populations, as well as neurotypical adults.
TUS delivers pressure waves to the target brain tissue for modulation7. Essential TUS hardware components include function generator(s), an amplifier, a transducer, and, especially for extended TSDs, an on-head transducer mount6. The function generator produces the electrical waveform that defines the exiting pressure pattern emitted by the transducer. While some function generators can generate the peak voltages required for TUS transducers, most require an amplifier to boost the signal between the function generator(s) and the transducer. The amplifier increases the amplitude of the electrical waveform to the level needed for effective ultrasound generation. Commercially available TUS systems often integrate the function generator and amplifier into a single turnkey unit, allowing direct connection to the transducer. The transducer, typically made of piezoelectric materials, converts the electrical signals into mechanical vibrations to produce ultrasound waves. Although manual transducer holding is possible, this approach is labor-intensive and susceptible to displacement errors, while a minor displacement can cause complete mistargeting of the intended tissue7. Mechanical arm with chin rest is also used and works well for basic research with relatively shorter TSDs. A feasible alternative for exploratory clinical TUS with TSDs over 10 min is 3D printing a transducer mount equipped with flanges for secure strap fixation (Figure 1), which can balance positional stability with ease of use in exploratory clinical settings and participant comfort.
<img alt="Head-mounted motion capture setup on mannequin, used for tracking head movements in research." class="xfigimg" src="/files/ftp_upload/69236/69236fig1.jpg" data-altupdatedat="1783396841000" data-alt="Figure 1"> 
Figure 1: 3D-printed mount for TUS transducer. Single-element transcranial ultrasonic stimulation (TUS) transducer (center piece pointed by the red arrow) housed in a 3D printed transducer mount (pointed by blue the arrow) with top openings (pointed by the green arrow) for neuronavigation's tool tracker, side openings (pointed by the brown arrow) to secure TUS transducer and tool tracker(s) using screws, and flanges for a strap-based on-head fixation. <a href="https://www.jove.com/files/ftp_upload/69236/69236fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Optional hardware components include an electrical impedance matching circuit, a power meter, an oscilloscope, a neuronavigation system, and a thermocouple. These devices respectively aid in reducing electrical reflections to optimize power transfer, indirectly verifying acoustic outputs (power meter and oscilloscope), ensuring spatial accuracy, and monitoring safety. Their implementation details and methodological considerations are elaborated in the Discussion and the Protocol sections.
Optimizing the parameters of transcranial ultrasound stimulation is an active and evolving area of research, which pertains to the design of the electrical drive waveform. The vertical axis of a drive waveform determines the amplitude of transducer's pressure output. The horizontal axis of a drive waveform determines the timing of the transducer's pressure output, which can be broken down into a few duration and repetition types. Using the nomenclature outlined in the reporting guidelines by the International Transcranial Ultrasonic Stimulation Safety and Standards Consortium (ITRUSST)10, TUS timing parameters are organized from the shortest to the longest durations as follows: ramp duration (RD) is the time during which the pressure output ramps up from zero to the prescribed maximum; pulse duration (PD) is the duration for a single, active, and continuous pressure output; pulse repeat interval (PRI) is the duration between the beginning of two adjacent PDs, consisting of one PD and one "off time" during which the transducer output is zero, and the reciprocal of PRI is the pulse repetition frequency (PRF); pulse train duration (PTD) is the duration for which the PRI is repeated; pulse train interval (PTI) is the duration between the beginning of two adjacent PTDs, consisting of one PTD and one inter-PTD interval during which the transducer output is zero; pulse train repeat duration (PTRD) is the duration for which the PTI is repeated.
<img alt="Ultrasound pulse diagram showing intervals: PTRD, PTI, PTD; waveform display; timing analysis." class="xfigimg" src="/files/ftp_upload/69236/69236fig2.jpg" data-altupdatedat="1783396841000" data-alt="Figure 2"> 
Figure 2: TUS waveform illustration. Typical transcranial ultrasonic stimulation waveforms for potential clinical efficacies. The nomenclature adheres to the ITRUSST reporting guidelines10. RD, ramp duration; PD, pulse duration; PRI, pulse repeat interval; PRF, pulse repetition frequency; PTD, pulse train duration; PTI, pulse train interval; PTRD, pulse train repeat duration. <a href="https://www.jove.com/files/ftp_upload/69236/69236fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Figure 2 illustrates these timing parameters. Table 1.1 reports the timing parameters in Huang et al., 20252, from which this protocol is derived, in accordance with the tabular form recommended by the ITRUSST reporting guidelines10 while Table 1.2 reports additional parameters. Auditory effects are widely recognized as a major confound in TUS experiments6,11. Ramping the drive waveform is the most used method to mitigate auditory effects and thus will be considered the primary mitigation method in this protocol. Theoretically, distinct ramping profiles can be applied at the start and end of each active pressure output (i.e., PD, PTD, PTRD), but most studies employ a same symmetrical PD repeated throughout the entire stimulation session, resulting a single RD in the drive signal. Ramping is implemented using window functions, which define the "shape" and "speed" of the signal going from zero to the prescribed maximum, with the Tukey window being the most commonly used in the literature10. After controlling for auditory confounds, selecting parameters to elicit excitatory versus inhibitory effect remains an area of active research and depends on the specific experimental question. Parameter choices in Huang et al., 20252, from which this protocol is derived, were informed by existing literature12, with a PD decreased from 0.36 ms to 0.2 ms for additional safety margins. Methodological aspects were adapted from Legon et al., 201813. These selections are one detailed example rather than a prescriptive standard, reflecting the still-exploratory stage of clinical TUS. Consult the relevant literature for guidance tailored to study-specific hypothesis and objectives.
Transducer calibration is a critical consideration of TUS, and water tank scanning represents the most comprehensive method currently available. For non-turnkey TUS systems, an initial water tank scanning is strongly recommended to establish the transmitting sensitivity of the transducer, i.e., the relationship between the electrical drive voltage in Volts and the resulting pressure output in Pascals. Turnkey systems often come with vendor-preconfigured settings that may reduce the need for an initial calibration, but verifying the transducer output ensures accurate and high-quality TUS delivery. Similarly, although subsequent calibrations can be minimized if necessary, regular checks are advisable to enhance study rigor.
Performing water tank scanning generally requires specialist equipment and training. This protocol provides a brief overview in Step 2 (based on Chen et al., 202314). Alternatively, the procedure can be outsourced to a collaborative laboratory with the appropriate expertise with confirmation that all required parameters are collected (Step 2.7). Power meter measurements provide a simple, indirect method for measuring transducer output. After calibration or vendor characterization, power meter readings can serve as a benchmark for pre-administration output. Variation in power output implies corresponding changes in pressure outputs, indicating a need for either re-calibration or adjustment of the drive signal to maintain consistent stimulation.
TUS targeting involves determining the optimal transducer placement, both location and orientation, to effectively stimulate the tissue of interest. The current state-of-the-art approach employs numerical simulations to identify the optimal transducer placement (Step 3 of the protocol), though this represents one example rather than a definitive standard. Alternatively, an empirically based method previously reported locates the scalp location where transcranial magnetic stimulation (TMS) most effectively elicits contralateral motor responses, and positions the transducer at that location with its surface normal to the scalp2,3 (Step 4). In principle, this TMS-guided approach can be extended to other brain areas that have an identifiable output, such as the sight of phosphenes for the visual cortex. However, more data/publications are needed to validate the broader applicability of such approach.
Outcome measures for clinical TUS include both safety and efficacy-based assessments. Given the exploratory stage of clinical translation, pronounced efficacy may not yet be detectable using standard clinical measures. Therefore, surrogate response indicators are often used in place of efficacy measures to detect effects below clinical efficacy. Safety monitoring can incorporate both online and offline assessments. Online safety can be tracked using thermocouple(s) placed on the scalp during stimulation, offering a practical approach in the clinical setting (Step 6.5). For offline safety, this protocol provides instructions in apparent diffusion coefficient (ADC) quantification (Step 8), as ADC is commonly used to evaluate tissue integrity15. Surrogate response indicators vary depending on the targeted disease or domain of interest. For studies of post-stroke motor recovery, contralateral corticospinal excitability (CSE) and motor sequence learning (MSL) measures will be described (Steps 9-11) as they provide reliable neurophysiological and functional markers for the exploratory clinical efficacy of TUS.
Taken together, this protocol provides a detailed, modular, and adaptable example for administering TUS in both neurological and neurotypical adults, emphasizing ease of use and extended stimulation duration. The protocol is derived from Huang et al., 20252, which employs a non-turnkey drive system that allows customization of pulse shaping and single-element transducer. In a step-by-step manner, the system-agnostic general principle is presented first, and, where appropriate, system-specific example implementation is given.

<table><tbody><tr><td>3D printer</td><td>UltiMaker</td><td>S3</td><td>To be used to manufacture the transducer mount.</td></tr><tr><td>3T MRI scanner</td><td>General Electric</td><td>Signa UHP</td><td></td></tr><tr><td>BabelBrain</td><td>Samuel Pichardo (University of Calgary)</td><td>Version 0.4.3</td><td>Referred in main text as the &quot;TUS targeting software.&quot; Accessible at https://proteusmrighifu.github.io/BabelBrain/</td></tr><tr><td>Brainsight</td><td>Rogue Research</td><td></td><td>Referred in main text as the &quot;neuronavigation software/system.&quot; To be used for TUS/TMS targeting, comes with a Mac computer, an infrared camera, and fiducials.</td></tr><tr><td>EMG amplifier and analog-to-digital converter&amp;nbsp;</td><td>Cambridge Electronic Design Ltd</td><td>CED 1902,&amp;nbsp; MICRO4</td><td>To be used to acquire, amplify, and digitize EMG signals.</td></tr><tr><td>dcm2niix</td><td>Christopher Rorden</td><td>V1.0.20250506</td><td>To convert neuroimages from DICOM to NIFTI. Accessible at https://pypi.org/project/dcm2niix/</td></tr><tr><td>E-prime</td><td>Psychology Software Tools</td><td>E-prime 3.0</td><td>Referred in main text as an example software for MSL. To be used to create the discrete sequence production task.</td></tr><tr><td>Fiducials and headband</td><td>Rogue Research</td><td>ST-1275 (subject tracker), LCT-494 (large coil tracker), P-1528 (pointer)</td><td>To be used in conjunction with Brainsight for neuronavigation.</td></tr><tr><td>FSL</td><td>University of Oxford</td><td></td><td>Referred in main text as the &quot;DTI processing software.&quot; To be used in the optional but recommended Step 8 for diffusion image processing.</td></tr><tr><td>Function generator</td><td>Keysight Technologies</td><td>33210A</td><td>To generate the drive signal for the TUS transducer.</td></tr><tr><td>Hydrophone</td><td>Onda Corporation</td><td>HNA-0400</td><td>To measure pressure output from the transducer.</td></tr><tr><td>ITK-SNAP</td><td>Penn Image Computing and Science Laboratory</td><td>ITK-SNAP 4.0</td><td>Referred in main text as an &quot;MRI viewer.&quot; Accessible at https://www.itksnap.org/pmwiki/pmwiki.php?n=Downloads.SNAP4</td></tr><tr><td>k-Wave</td><td>Bradley Treeby, Ben Cox, and Jiri Jaros</td><td>k-Wave Version 1.4</td><td>Referred in main text as the &quot;open-source acoustic simulation software.&quot; Accessible at http://www.k-wave.org/</td></tr><tr><td>MATLAB</td><td>MathWorks Inc.</td><td>R2024b</td><td>Referred in main text as the &quot;programming platform.&quot; Accessible at https://www.mathworks.com/products/matlab.html</td></tr><tr><td>MRIcroGL</td><td>NeuroImaging Tools &amp;amp; Resources Collaboratory</td><td>v1.2.20220720</td><td>To convert neuroimages from DICOM to NIFTI. Accessible at https://www.nitrc.org/projects/mricrogl/</td></tr><tr><td>MRIcron</td><td>NeuroImaging Tools &amp;amp; Resources Collaboratory</td><td>v1.0.20190902</td><td>Referred in main text as an &quot;MRI viewer.&quot; Accessible at https://www.nitrc.org/projects/mricron</td></tr><tr><td>Oscilloscope</td><td>SIGLENT Technologies</td><td>SDS 1202X-E</td><td>To be used to measure the input of TUS transducer and to record hydrophone measurements.</td></tr><tr><td>Python</td><td>Python Software Foundation</td><td>Python 3.13</td><td>Referred in main text as an example language for MSL. To be used to create the discrete sequence production task.</td></tr><tr><td>RF power amplifier</td><td>AR RF/Microwave Instrumentation</td><td>50A250</td><td>To be used to amplifier the output of function generators to the amplitude required by the TUS transducer.</td></tr><tr><td>Signal</td><td>Cambridge Electronic Design Ltd</td><td>Signal 7.05a (x86)</td><td>Referred in main text as the &quot;EMG acquisition software.&quot; To be used to acquire EMG signals from the analog-to-digital converter to a computer.</td></tr><tr><td>SimNIBS</td><td>Axel Thielscher (Technical University of Denmark)</td><td>Version 4.5</td><td>Referred in main text as the &quot;e-field software.&quot; Accessible at https://simnibs.github.io/simnibs/build/html/index.html</td></tr><tr><td>SPM12</td><td>Functional Imaging Laboratory (University College London)</td><td></td><td>Referred in main text as the &quot;MRI processing software.&quot; To be used in the optional but recommended Step 8 for MRI image processing.</td></tr><tr><td>TMS stimulator and coil</td><td>Magstim Inc.</td><td>BiStim&lt;sup&gt;2&lt;/sup&gt;, 70 mm figure-of-eight</td><td>To be used to apply TMS pulses.</td></tr><tr><td>Transducer</td><td>Blatek Industries</td><td>AT32080</td><td></td></tr><tr><td>Transducer mount</td><td>Duke University team</td><td></td><td>3D printed tranducer mount in polyactic acid (PLA) and added with fabric straps.</td></tr><tr><td>Ultrasound gel</td><td>Parker Laboratories</td><td>Aquasonic 100</td><td>To be applied between the TUS transducer and participant scalp.</td></tr><tr><td>Water tank and 3-axis positioning system</td><td>Onda Corporation</td><td>AIMS III Hydrophone Scanning System</td><td>Customized with the company.</td></tr></tbody></table>

a methodological protocol and considerations for transcranial ultrasonic stimulation in exploratory clinical human studies

A Methodological Protocol and Considerations for Transcranial Ultrasonic Stimulation in Exploratory Clinical Human Studies

Transcranial ultrasonic stimulation (TUS) is emerging as a non-invasive neuromodulatory technique capable of delivering millimeter-precision stimulation at whole-brain depths. Research efforts have increasingly focused on its translational potential. Promising data have been reported across several disease populations, including Parkinson's disease and stroke, paving the way for clinical applications of TUS. Clinical studies to date, however, show substantial variability in transducer fixation, targeting approaches, and acoustic parameters. This limits the interpretability and comparability of results. Existing methodological guides address human TUS in general but do not focus on applications in neurological populations. This experimental protocol presents a standardized yet adaptable framework for applying TUS to neurological cohorts such as stroke. It offers detailed guidance on: (1) essential and optional hardware components in the context of therapy-oriented TUS; (2) hardware settings and parameter selection, including strategies to minimize auditory confounds; (3) calibration and quality assurance procedures to ensure the transducer delivers waveforms as specified; (4) targeting approaches based on simulation or non-simulation methods for accurate localization of TUS focus/foci to the intended anatomical region(s); (5) methodology adaption for clinical populations; and (6) outcome measures for clinical TUS, encompassing safety assessments and surrogate outcome measures such as corticospinal excitability and motor sequence learning. This protocol is designed as a replicable, modular resource. It accommodates both novice users (seeking a practical entry point into patient-based TUS) and experienced researchers (aiming to align with emerging scientific and methodological standards). The goal is to support the growing clinical interest in TUS and to facilitate clinically translatable, reproducible, and comparable results across research groups and patient populations.

Simulation-based TUS targeting first defines an initial transducer placement manually based on proximity to the intracranial target and perpendicularity to the skull and uses this initial placement and transducer specifications to solve for the intracranial acoustic field. Next, it computes the discrepancy between the intended stimulation target and the acoustic field focus, updates the transducer placement in the reverse direction of this discrepancy, solves for the acoustic field using this new transducer placement, an...

Transcranial ultrasonic stimulation (TUS) is a promising non-invasive technique capable of stimulating the human brain at any depth, offering new therapeutic possibilities to treat various neurological conditions. This protocol provides a standardized yet adaptable empirical framework for applying TUS in neurotypical adults and patients with neurological diseases such as stroke.

Transcranial ultrasonic stimulation (TUS) is emerging as a non-invasive neuromodulatory technique capable of delivering millimeter-precision stimulation ...

Our neuromodulation and the Stroke Recovery Lab focus on using various neuromodulation tools to enhance post-stroke recovery, including motor recovery. This particular project involves using low-intensity transcranial ultrasound stimulation, a new non-invasive brain stimulation tool to modulate the motor cortex excitability and promote motor learning in stroke patients. To begin, prepare a water tank with degassed deionized water to prevent potential damage to the hydrophone.Fixate the ultrasound transducer onto the fixture on the water tank, and mount the hydrophone onto the three-axis positioning system. Connect the hydrophone to an oscilloscope and then connect the needle tip along with the cable. Switch on the hydrophone power only after it is fully immersed in water.Drive the ultrasound transducer using a function generator. Then position the hydrophone tip at the approximate focal region of the ultrasound transducer using the three-axis positioning system. Record the oscilloscope readings at each location to obtain the acoustic pressure distribution and document the hydrophone location corresponding to the focal region.Assess the transmitting sensitivity of the ultrasound transducer at the focal point by applying different input voltages. Connect the transcranial ultrasound stimulation hardware and start oscilloscope recording. Turn on the oscilloscope.Set it to run and adjust both vertical and horizontal axes to the scale of interest. Flip the main power switch of the amplifier to the On position. Dial the power output of the amplifier to zero.Configure both function generators to the desired waveform, ensuring ramping is added to each pulse duration. Now press Output on the function generator. Dial the amplifier output to 100%using the adjust wheel and monitor the gain display.Press the amplifier power button to start its output. Confirm the drive signal waveform on the oscilloscope, and allow the drive system to run for 15 minutes to stabilize the output. Check for ramping at the beginning and end of each pulse duration on the drive signal waveform.Dial the amplifier output to zero. Fully immerse the transducer in water, positioning the exit plane approximately one inch below the surface facing upward. Then dial the amplifier output back to 100%and observe whether the ramping is successful.Now mount a neuro navigation tool tracker onto the transducer holder. In the software, navigate to Window and Tool Calibrations. Click New Calibration.Enter a name and select the correct tool tracker. Hold the transducer with the tracker against the calibration block, such that the reference indicator pin touches and is perpendicular to the center of the transducer's exit plane. Click Begin Calibration Countdown.Hold steady for five seconds and repeat if necessary until success appears. Then close both Edit Calibration and Tool Calibrations windows. Press the amplifier power button to turn off its output when the participant is ready for transcranial ultrasound stimulation.Disconnect the oscilloscope from the amplifier and connect the transducer to the amplifier output. If using the simulation-based target, load the target into the neuro navigation software. In the Sessions tab, open the new dropdown and select Online Session.Under the Targets tab, click on the Trajectory-x-mod target and press Add to add it for the session. Bring up the bullseye tool centric or bullseye target centric view in the Perform window. Set the driver to the correct TUS transducer and select the correct target in the Targets to sample list on the upper left.Comb the participant's hair to expose the scalp at the TUS transducer site and create an anterior/posterior parting line. Apply the gassed ultrasound gel along it. Create one to three additional parting lines approximately 1.5 centimeters away on each side, and repeat the same process.Finally, return to the initial parting line and repeat the process four times. Now, strap the TUS transducer onto the participant's head and align it with the target using the bullseye view. Adjust the transducer to minimize distance, tilting, and rotational deviations to within operational limits.If safety monitoring is required, insert a thermocouple wire into the ultrasound gel close to the scalp. Tape the thermocouple wire on the head using paper tape to prevent movement. Press the amplifier's power button to start output and begin TUS.Simultaneously press Sample Now on the neuro navigation software to record initial transducer placement. Continuously monitor the three alignment metrics in the bullseye view. Monitor the scalp temperature using the thermocouple wire if installed.To finish TUS, press the amplifier power button to stop the output. Remove the transducer and all head-mounted equipment from the participant. Inspect the scalp for any signs of redness, and ask the participant about any discomfort or adverse effects.If no issues are reported or after addressing concerns, gently wipe off the ultrasound gel from the scalp. Click Finish on the neuro navigation window and save the project by selecting File and pressing Save Project. From the sessions list, select the current session and click Review.In the Sessions Review window, choose brain site text file from the Export dropdown menu. Ensure Orientation is selected and set Snap to to Nothing. Configure other export settings as needed, then click Save to export the stimulation data.A satisfactory simulation based targeting result was achieved where the acoustic focus reached the intended cortical stimulation region. A scenario in simulation-based targeting that requires additional iterations due to misalignment between the acoustic focus and the intended stimulation target. Adjusting the Distance TX out plane to skin parameter to a more realistic value to correct the visualization scaling issue in the simulation interface.A clean motor evoked potential was recorded, indicating good transcranial magnetic stimulation, coil placement, and orientation. A waveform was observed that might not represent a motor evoked potential. A successful MT one millivolt determination was made at 52%maximum stimulator output, with five positive and five negative responses at that level.A potentially inconclusive MT one millivolt determination was recorded at 87%maximum stimulator output due to consecutive, rather than alternating positive and negative responses. A steady, even oscilloscope reading of the transducer driving signal was obtained, indicating proper equipment function. Good alignment was achieved between the physical transducer placement and the predefined target using neuro navigation.A misaligned transducer placement was observed, indicating the need for adjustment to match the target. We established TUS safety and effective intensity in stroke patients showing motor cortex TUS can enhance motor learning and cortical excitation. There's no methodological article focusing on the use of TUS in neurologically disease adults.This protocol addresses this gap. We hope this protocol can reduce the methodological variability and improve the reliability and reproducibility of future human ultrasound studies.

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Research

JoVE Journal

Medicine

Transcranial magnetic stimulation (TMS) is a technique for non-invasively disrupting neural information processing and measuring its effect on behavior. When TMS interferes with a task, it indicates that the stimulated brain region is necessary for normal task performance, allowing one to systematically relate brain regions to cognitive functions.

Transcranial Magnetic Stimulation for Investigating Causal Brain-behavioral Relationships and their Time Course

The development of new ultrasound (US) probes based on Capacitive Micromachined Ultrasonic Transducer (CMUT) technology requires an early realistic assessment of imaging capabilities. We describe a repeatable experimental protocol for US image acquisition and comparison with magnetic resonance images, using an ex vivo bovine brain as an imaging target.

An Experimental Protocol for Assessing the Performance of New Ultrasound Probes Based on CMUT Technology in Application to Brain Imaging

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Remotely Supervised Transcranial Direct Current Stimulation: An Update on Safety and Tolerability

This protocol describes a surgical set-up for a permanent epicranial electrode socket and an implanted chest electrode in rodents. By placing a second electrode into the socket, different types of transcranial electrical brain stimulation can be delivered to the motor system in alert animals through the intact skull.

Transcranial Electrical Brain Stimulation in Alert Rodents

This detailed protocol describes transcranial stimulation electrode placement on the temporal bone in order to investigate the short- and long-term effects of transcranial electrical stimulation in freely moving rats.

Chronic Transcranial Electrical Stimulation and Intracortical Recording in Rats

The combined use of transcranial direct current stimulation and robotic therapy as an add-on for conventional rehabilitation therapy may result in improved therapeutic outcomes due to modulation of brain plasticity. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.

The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb

This article describes new approaches to measure and strengthen functionally specific neural pathways with transcranial magnetic stimulation. These advanced noninvasive brain stimulation methodologies can provide new opportunities for the understanding of brain-behavior relations and development of new therapies to treat brain disorders.

Measuring and Manipulating Functionally Specific Neural Pathways in the Human Motor System with Transcranial Magnetic Stimulation

Transcranial ultrasound stimulation (TUS) is an emerging non-invasive neuromodulation technique that requires careful planning of acoustic and thermal simulations. The methodology describes an image processing and ultrasound simulation pipeline for efficient, user-friendly, streamlined planning for human TUS experimentation.

Pipeline for Planning and Execution of Transcranial Ultrasound Neuromodulation Experiments in Humans

This protocol describes the method of neuronavigated electrode placement for focal, transcranial direct current stimulation (tDCS) administered during functional magnetic resonance imaging (fMRI).

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This protocol establishes a practical approach for combining HD-tACS with EEG to examine stimulation effects on neural oscillations during cognitive tasks, using theta-frequency stimulation in working memory as an exemplar.

The Combination of Transcranial Alternating Current Stimulation and Electroencephalogram

Learn transcranial ultrasonic stimulation for non-invasive neuromodulation in stroke recovery. This protocol establishes safety measures and standardized procedures for enhancing motor cortex excitability in patients.

A Methodological Protocol and Considerations for Transcranial Ultrasonic Stimulation in Exploratory Clinical Human Studies

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