Name: Localizing Function-specific Targets for Transcranial Magnetic Stimulation in the Absence of Navigation Equipment (Video) | JoVE Journal
Uploaded: 2025-05-23T13:10:00.000+00:00
Duration: 9 min 30 s
Description: Learn to localize function-specific TMS targets without navigation equipment using individual activation maps and cognitive performance. This method enables personalized brain stimulation for motor cognitive neuroscience research.

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This study was supported by the Sichuan Province Science and Technology Support Program (No. 2024ZYD0189). The authors would like to thank the PREcision medicine Consortium for Imaging-guided transcranial magnetic Stimulation thErapy (PRECISE) for their professional guidance.

<ol><li>Aşkın, A., Tosun, A., Demirdal, ÜS. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effects+of+low-frequency+repetitive+transcranial+magnetic+stimulation+on+upper+extremity+motor+recovery+and+functional+outcomes+in+chronic+stroke+patients%3A+A+randomized+controlled+trial%5BTitle%5D)+AND+%22Somatosens+Mot+Res%22%5BJournal%5D)">Effects of low-frequency repetitive transcranial magnetic stimulation on upper extremity motor recovery and functional outcomes in chronic stroke patients: A randomized controlled trial.</a> Somatosens Mot Res. 34 (2), 102-107 (2017).</li>
<li>Du, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effects+of+repetitive+transcranial+magnetic+stimulation+on+motor+recovery+and+motor+cortex+excitability+in+patients+with+stroke%3A+a+randomized+controlled+trial%5BTitle%5D)+AND+%22Eur+J+Neurol%22%5BJournal%5D)">Effects of repetitive transcranial magnetic stimulation on motor recovery and motor cortex excitability in patients with stroke: a randomized controlled trial.</a> Eur J Neurol. 23 (11), 1666-1672 (2016).</li>
<li>Tosun, A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effects+of+low-frequency+repetitive+transcranial+magnetic+stimulation+and+neuromuscular+electrical+stimulation+on+upper+extremity+motor+recovery+in+the+early+period+after+stroke%3A+a+preliminary+study%5BTitle%5D)+AND+%22Top+Stroke+Rehabil%22%5BJournal%5D)">Effects of low-frequency repetitive transcranial magnetic stimulation and neuromuscular electrical stimulation on upper extremity motor recovery in the early period after stroke: a preliminary study.</a> Top Stroke Rehabil. 24 (5), 361-367 (2017).</li>
<li>Wang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Function-Specific+localization+in+the+supplementary+motor+area%3A+A+potential+effective+target+for+Tourette+syndrome%5BTitle%5D)+AND+%22CNS+Neurosci+Ther%22%5BJournal%5D)">Function-Specific localization in the supplementary motor area: A potential effective target for Tourette syndrome.</a> CNS Neurosci Ther. 31 (2), e70280(2025).</li>
<li>Wang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Finger+tapping+task+activation+vs.+TMS+Hotspot%3A+Different+locations+and+networks%5BTitle%5D)+AND+%22Brain+Topogr%22%5BJournal%5D)">Finger tapping task activation vs. TMS Hotspot: Different locations and networks.</a> Brain Topogr. 33 (1), 123-134 (2020).</li>
<li>Wang, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Low-frequency+rTMS+targeting+individual+self-initiated+finger-tapping+task+activation+modulates+the+amplitude+of+local+neural+activity+in+the+putamen%5BTitle%5D)+AND+%22Hum+Brain+Mapp%22%5BJournal%5D)">Low-frequency rTMS targeting individual self-initiated finger-tapping task activation modulates the amplitude of local neural activity in the putamen.</a> Hum Brain Mapp. 44 (1), 203-217 (2023).</li>
<li>Hu, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Caliper-based+precise+positioning+of+the+target+%28CALIPPOT%29+for+transcranial+magnetic+stimulation+without+neuronavigation+system%5BTitle%5D)+AND+%22Gen+Psychiatr%22%5BJournal%5D)">Caliper-based precise positioning of the target (CALIPPOT) for transcranial magnetic stimulation without neuronavigation system.</a> Gen Psychiatr. 37 (2), e101262(2024).</li>
<li>Jiang, Y., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((A+scalp-measurement+based+parameter+space%3A+Towards+locating+TMS+coils+in+a+clinically-friendly+way%5BTitle%5D)+AND+%22Brain+Stimul%22%5BJournal%5D)">A scalp-measurement based parameter space: Towards locating TMS coils in a clinically-friendly way.</a> Brain Stimul. 15 (4), 924-926 (2022).</li>
<li>Weiduschat, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Localizing+Broca%27s+area+for+transcranial+magnetic+stimulation%3A+Comparison+of+surface+distance+measurements+and+stereotaxic+positioning%5BTitle%5D)+AND+%22Brain+Stimul%22%5BJournal%5D)">Localizing Broca's area for transcranial magnetic stimulation: Comparison of surface distance measurements and stereotaxic positioning.</a> Brain Stimul. 2 (2), 93-102 (2009).</li>
<li>Liu, F., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((MNI2CPC%3A+A+probabilistic+cortex-to-scalp+mapping+for+non-invasive+brain+stimulation+targeting%5BTitle%5D)+AND+%22Brain+Stimul%22%5BJournal%5D)">MNI2CPC: A probabilistic cortex-to-scalp mapping for non-invasive brain stimulation targeting.</a> Brain Stimul. 16 (6), 1733-1742 (2023).</li>
<li>A transcranial magnetic stimulation targeting ruler. China patent. , ZL202111010713.2 (2025).</li>
<li>The method for non-navigated, individualized rTMS function-specific target localization. China patent. , ZL202411874788.9 (2025).</li>
</ol>

The authors have no conflicts of interest to declare.

In this study, we propose the concept of function-specific targets, which are brain regions associated with specific functions identified through neuroimaging techniques. Inspired by previous studies8,9,10, we developed a new toolkit7,11,12 for locating scalp targets corresponding to function-specific cortical areas, enabling function-specific targeted rTMS without the need for navigation equipment. Compared to stimulation using navigation equipment, no significant differences in brain function effects were observed. This suggests that, in certain cases, our method can achieve individualized function-specific targeted rTMS without the need for expensive navigation equipment.
Essential steps in the experimental protocol 
To ensure the accuracy of non-navigated rTMS localization, the operator must align the scale on the targeting ruler with the left and right ear landmarks, the nasion, and the inion. The scale should be firmly pressed against the scalp surface to minimize measurement errors caused by hair thickness. This process is crucial for improving localization accuracy and ensuring precise targeting of the stimulation site.
Improvements to experimental method and potential technical issues 
Since this method is an advanced version of a previously developed technique11, no areas for improvement have been identified so far. Regarding potential technical issues, individual differences in skull shape may result in less prominent occipital protuberances in some participants, which could lead to localization errors. In such cases, the occipital protuberance can be omitted, and other landmarks (such as the left and right ear markers and the nasion) can be used for localization without compromising accuracy, as redundancy has already been factored into the development phase.
Limitations of the non-navigated rTMS method 
The main difference compared to navigated rTMS is the inability to monitor the coil&#39;s relative distance and direction to the stimulation target in real-time. However, even with navigated rTMS, real-time monitoring still requires experienced operators to make manual adjustments.
Significance of the experimental method in relation to existing methods 
Compared to navigation equipment, our method does not require lengthy positioning or equipment calibration. Instead, users simply input MRI data into the code script and then calculate the corresponding distances via code, after which positioning is quickly completed using a measuring tool. Based on our experience, this method saves at least 15 minutes compared to the complex procedures involved in navigation. Navigation equipment typically requires expensive hardware and specialized training, while our method only requires MRI images and standard calculations to achieve fast, convenient, and precise localization, significantly reducing both upfront costs and operational complexity.
In terms of cost, our measuring tool has been granted an invention patent (ZL202411874788.9)12., which helps protect the intellectual property but does not significantly increase production costs. 3D modeling is currently underway, and we will soon be able to 3D print the tool for our clinical collaborators. Cost considerations were integrated into the design phase from the outset. For non-collaborators wishing to purchase the tool, the price is only 500 CNY (approximately 70 USD), which remains affordable despite the patent protection.
Importance and potential applications of the method in specific research fields 
rTMS intervention and treatment have gained increasing popularity in both research and clinical fields in recent years. Like all therapeutic techniques, the development is moving toward precise, individualized treatments targeting specific functions. However, navigation systems and equipment are expensive, and most hospitals in China currently do not have access to such devices. This method addresses the issue of individualized, function-specific targeted rTMS without the need for navigation. It projects cortical target coordinates onto the scalp and uses a tool to mark the coordinates on the scalp surface. The fMRI-based cortical targeting method used in this approach is identical to the fMRI target coordinates employed by navigation systems and equipment internationally. Although it cannot monitor the real-time relative distance and direction between the coil and the stimulation target, it still offers advantages over current clinical &#34;blind targeting&#34; methods (such as using anatomical landmarks on the skin surface or selecting the hand motor hotspot). This method serves as a transitional approach between precise real-time navigation and &#34;blind targeting&#34;. For clinical institutions without navigation systems and equipment, it can solve practical clinical problems. This method will significantly promote fMRI-guided TMS precision treatment, leading to the discovery of more effective stimulation targets and improving the efficacy of treatments for various neurological and psychiatric disorders.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that can regulate brain activity and has been widely used in the treatment of neuropsychiatric disorders, such as in the rehabilitation of hand motor dysfunction in stroke patients. Some studies have shown that rTMS has therapeutic effects on post-stroke sequelae1,2,3, but its efficacy remains uncertain. One key reason for this uncertainty is the difficulty in identifying precise stimulation targets. TMS studies targeting motor function often rely on the International 10-20 Electroencephalogram system for localization, using C3/C4 as the stimulation targets, or they employ individualized targets, such as the hand motor hotspot. However, these methods cannot accurately determine the cortical areas affected by TMS. Functional magnetic resonance imaging (fMRI)-guided, targeted rTMS has been widely used in the treatment of depression.
Our previous research also explored its application in treating Tourette syndrome by stimulating supplementary motor area4, but it has not yet been applied to the primary motor area (M1). For rTMS, M1 is distinct from other brain regions because it contains the hand motor hotspot. The muscle contractions induced by TMS represent involuntary movements, reflecting top-down conduction through the corticospinal or pyramidal tracts. In contrast, the activation peak voxels defined by fMRI during finger tapping tasks are more functionally connected to brain regions involved in motor cognition, representing voluntary movements5. Therefore, when treating movement disorders, using the task-related &#34;activation&#34; defined by fMRI as function-specific targets may lead to improved therapeutic outcomes5,6. In our previous work, we compared brain activation patterns between the visual-guided task and the self-initiated task using fMRI and determined that the self-initiated task more closely aligns with the requirements of active rehabilitation training6. We confirmed this finding by reanalyzing a subset of data from the original study (Figure 1).
Accurately targeting specific brain function areas requires precise navigation tools. However, current systems are not only cumbersome to operate and limited in functionality, but the head-mounted calibrators often fail to remain stable during procedures, are prone to shifting, and are expensive -- sometimes costing up to one million Chinese Yuan (CNY), approximately 140,000 United States Dollar (USD). According to a survey on the usage patterns among member institutions of the Precision Medicine Consortium for Imaging-Guided Transcranial Magnetic Stimulation Therapy (PRECISE), these drawbacks have led to navigation technologies being used in less than 5% of TMS research and clinical practice in China, despite their potential benefits. More importantly, however, is that these systems only focus on &#34;locating&#34; stimulation sites without addressing the critical issue of &#34;defining&#34; the target, i.e. selecting the most appropriate area for stimulation. Given the high costs, operational complexity, and time demands, this is why these devices have yet to achieve widespread clinical adoption.
To address the challenge of using function-specific targets without navigational devices, we explored the method of non-navigated, targeted rTMS. Using fMRI, we identified function-specific targets in the motor cortex and projected them onto the scalp surface, allowing for target definition and localization without the need for navigation equipment7. While non-navigated rTMS does not provide real-time monitoring throughout the entire process, it addresses the issues of precision in target localization under clinical conditions where navigational devices are unavailable. This paper elaborates on the overall study rationale and outlines the complete experimental process, with a particular focus on comparing the effects of function-specific targets on brain function under both navigated and non-navigated conditions. To verify the feasibility of function-specific targeted rTMS, the current study only included healthy individuals.

<table><tbody><tr><td>Brainsight Neuronavigation system</td><td>Rogue Research Inc.</td><td>KITBSF0104</td><td></td></tr><tr><td>DPABI_V7.0 toolkit&amp;nbsp;</td><td>DeepBrain</td><td></td><td>for RS-fMRI and task-based fMRI data analysis</td></tr><tr><td>Magstim Rapid&lt;sup&gt;2&lt;/sup&gt;</td><td>The MAGSTIM Company Limited&amp;nbsp;</td><td>3012-00</td><td></td></tr><tr><td>SPM12 (7771)&amp;nbsp;</td><td>Wellcome Centre for Human Neuroimaging</td><td></td><td>for RS-fMRI and task-based fMRI data analysis</td></tr><tr><td>The Brainsight 2 channel electromyography acquisition device</td><td>Rogue Research Inc.</td><td>NTBX001001</td><td></td></tr></tbody></table>

localizing function-specific targets for transcranial magnetic stimulation in the absence of navigation equipment

Localizing Function-specific Targets for Transcranial Magnetic Stimulation in the Absence of Navigation Equipment

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that modulates neural activity in the brain. Studies have shown that rTMS can regulate neural plasticity, promote neural network reorganization, and has been widely applied to neuropsychiatric disorders such as stroke. Although some studies suggest that rTMS can aid in stroke rehabilitation, its efficacy remains uncertain, possibly because of limitations in the traditional localization of the hand motor hotspot.
The hand motor hotspot is determined by motor evoked potentials (MEPs), which reflect the conductivity of the corticospinal or pyramidal tract, representing non-voluntary movement. In contrast, functional magnetic resonance imaging (fMRI) activation points from a motor task define function-specific targets, which involve both perception and motor execution, representing voluntary movement. Based on this, we propose the concept of function-specific targets -- targets identified through brain imaging techniques aimed at specific functions. Function-specific targets exhibit stronger and more extensive functional connectivity with brain regions related to motor cognition, potentially offering more effective regulatory effects than the hotspots.
We explored and validated the modulatory effects of function-specific targets in previous study. However, institutions without navigation equipment are unable to utilize these function-specific targets. Therefore, we have developed a non-navigated localization method for function-specific targets, specifically designed to define and localize rTMS targets in the post-stroke ipsilateral hemisphere, addressing the challenges faced by institutions lacking navigation equipment when applying function-specific targeted rTMS.

The paired t-test and two-way ANOVA results indicated that there were no significant differences in the changes in ALFF or FC before and after rTMS under both navigated and non-navigated conditions (GRF correction, voxel p &lt; 0.001, cluster p &lt; 0.05). No significant differences were observed between the navigation and non-navigation conditions. This result aligns with our expectations, indicating that our non-navigation method does not have a significant disadvantage compared to the navigation method. To avoid making unsupported claims of no significant differences, we present the one-sample t-test maps for both rTMS conditions here (uncorrected, voxel p &lt; 0.05) (Figure 5). These results do not survive any type of multiple comparison adjustment, such as FDR or GRF correction. To assess the equivalence of brain function changes induced by the non-navigated and navigated methods, a power analysis was conducted using Cohen's d. The results indicated that the Cohen's d value for ALFF was 0.22, while the Cohen's d value for FC was 0.56.
<img alt="Functional connectivity diagrams; fMRI activation; self-initiated vs visual-guided tasks; T value map." class="xfigimg" src="/files/ftp_upload/67888/67888fig01.jpg" data-altupdatedat="1788304762000" data-alt="Figure 1"> 
Figure 1: Results for paired t-tests. (A) The differences between activation-based and APB hotspot-based functional connectivity (GRF correction, single voxel p &lt; 0.001, cluster level p &lt; 0.05). (B) The differences in brain activation between self-initiated and visual-guided finger tapping tasks in 25 participants (FDR correction, q &lt; 0.05). (C) The differences between self-initiated and visual-guided state activation-based functional connectivity in 35 participants (GRF correction, single voxel p &lt; 0.001, cluster p &lt; 0.05). Figure 1A was adapted from Wang et al. (2020)5; Figure 1B,C were prepared by extracting a different subset of data from Wang et al. (2023)6. Abbreviations: APB = Abductor Pollicis Brevis; GRF = Gaussian Random Field; FDR = False Discovery Rate. <a href="https://www.jove.com/files/ftp_upload/67888/67888fig01large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Neuroscience study process diagram showing MRI, EMG, rTMS, and fMRI data analysis steps." class="xfigimg" src="/files/ftp_upload/67888/67888fig02.jpg" data-altupdatedat="1788304762000" data-alt="Figure 2"> 
Figure 2: Experimental design flowchart. <a href="https://www.jove.com/files/ftp_upload/67888/67888fig02large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Geometric diagrams illustrating angles, circles, protractor, and ruler for math measurement concepts." class="xfigimg" src="/files/ftp_upload/67888/67888fig03.jpg" data-altupdatedat="1788304762000" data-alt="Figure 3"> 
Figure 3: Schematic diagram of the targeting ruler. (A) Front view of the targeting ruler. 1. Handle; 2. Scalp anchor point (i.e., the scalp origin in the XY plane); 3. Rigid measuring ruler (acrylic material); 4. Rotatable and flexible measuring ruler (silicone material). (B) Magnified view of the scalp anchor point (i.e., an enlarged view of 2 in A). (C) Magnified view of the flexible measuring ruler (i.e., enlarged views of 3 and 4 in A). <a href="https://www.jove.com/files/ftp_upload/67888/67888fig03large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Brain mapping process; Euclidean distance in activation peak voxel diagram; neuroscience setup." class="xfigimg" src="/files/ftp_upload/67888/67888fig04.jpg" data-altupdatedat="1788304762000" data-alt="Figure 4"> 
Figure 4: Conversion of the function-specific cortical target to the function-specific scalp target. The red dot represents the function-specific cortical target, the green dot represents the function-specific scalp target, and the blue dot indicates the origin of the 2D coordinate system on the scalp. <a href="https://www.jove.com/files/ftp_upload/67888/67888fig04large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="fMRI brain t-test maps, rTMS conditions, FC and ALFF analysis, non-navigated vs. navigated results." class="xfigimg" src="/files/ftp_upload/67888/67888fig05.jpg" data-altupdatedat="1788304762000" data-alt="Figure 5"> 
Figure 5: Results for one-sample t-tests. (A) Non-navigated rTMS modulatory effects on brain function (p &lt; 0.05, uncorrected). (B) Navigated rTMS modulatory effects on brain function (p &lt; 0.05, uncorrected). Abbreviations: FC = functional connectivity; ALFF = amplitude of low-frequency fluctuation; rTMS = repetitive transcranial magnetic stimulation. <a href="https://www.jove.com/files/ftp_upload/67888/67888fig05large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
Supplemental File 1: Parameters used in the DPARSF Advanced Edition, as mentioned in protocol section 4.1.1. <a href="https://www.jove.com/files/ftp_upload/67888/JoVE67888R2_screenfile1.zip" target="_blank">Please click here to download this File.</a>
Supplemental File 2: The zip folder containing the MATLAB code used in this study. <a href="https://www.jove.com/files/ftp_upload/67888/Get_ScalpTarget.zip" target="_blank">Please click here to download this File.</a>
Supplemental Figure S1: Self-initiated finger tapping task. The task consisted of eight blocks, each duration lasting 30 s, resulting in a total length of 4 min. <a href="https://www.jove.com/files/ftp_upload/67888/Fig%20S1.tiff" target="_blank">Please click here to download this File.</a>

This paper describes how to localize function-specific targets for repetitive transcranial magnetic stimulation interventions or treatments when navigation equipment is unavailable.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that modulates neural activity in the brain. Studies have shown that rTMS ...

localizing-function-specific-targets-for-transcranial-magnetic

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Learn to localize function-specific TMS targets without navigation equipment using individual activation maps and cognitive performance. This method enables personalized brain stimulation for motor cognitive neuroscience research.

Localizing Function-specific Targets for Transcranial Magnetic Stimulation in the Absence of Navigation Equipment

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