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Changing Brain Networks Through Non-invasive Neuromodulation
Open accessAbstract
Background/Objective: Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this paper, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method: This paper addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that support this hypothesis from different perspectives. Main Results/Conclusion: Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex, have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks.
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“rTMS uses focused magnetic field pulses to modify neural activity at the stimulation site and can induce structural and functional connectivity changes in distributed brain networks, 14 including the cognitive control network.”
From Cognitive Outcomes After Transcranial Magnetic Stimulation for the Treatment of Late-Life Depression: Résultats cognitifs après la stimulation magnétique transcrânienne pour le traitement de la dépression chez les personnes âgées (2026) · cites this paper as [14]
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“from outside the skull) enhance internal information processing, like noninvasive neuromodulation (To et al. 2018).”
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“One such requirement is to gauge focality when multiple ROIs (or network of ROIs) need to be targeted (To et al., 2018).”
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“Non-invasive neuromodulators affect the brain network as a whole and do not singularly target the local stimulation site [15]; therefore, we can explore the effect of different electrical stimulation experiments by analyzing the connectivity and complexity of the brain network before and after stimulation.”
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Gorka, S. M., Jimmy, J., Koning, K. M., Phan, K. L., Rotstein, N. M., Dang, B. H., Halavi, S. E., Spivak, N. M., Monti, M. M., Reggente, N., et al. (2024) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2024.1486770 · Cited by 9
Intrinsic functional connectivity correlates of pro-environmentalism
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“Low-frequency rTMS (= 1 Hz) has been associated with inhibitory effects on neuroplasticity (To et al., 2018).”
Targeting network hubs with noninvasive brain stimulation in patients with fibromyalgia
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“However around 30% of this clinical group does not respond to either behavioral therapy or anti-depressive medication having led to the search for alternative therapies including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current Sstimulation (tDCS) and vagal nerve stimulation (VNS) [6,7].”
BackgroundNoninvasive Brain Stimulation: An Overview of Available Approaches for Research in Neuroaesthetics
Cattaneo, Z. (2018) · Empirical Studies of the Arts · doi:10.1177/0276237418818637 · Cited by 9
Multisite non-invasive brain stimulation in Parkinson’s disease: A scoping review
Machado, C. B. D. S., da Silva, L. M., Gonçalves, A. F., de Andrade, P. R., Mendes, C. K. T. T., de Assis, T. J. C. F., Júnior, C. D. O. G., & Andrade, S. M. (2021) · Neurorehabilitation · doi:10.3233/nre-210190 · Cited by 8
“Changes in cortical networks by NIBS have been reported in previous studies (Hess, 2013; To et al., 2018), however, the dynamic of these effects depends of methodological issues, such as time, electrode montage and stimulation parameters (Deng et al.”
MethodBenrimoh, D. A., Azeez, A., Batail, J.-M. V., Xiao, X., Buchanan, D. M., Bandeira, I. D., Geoly, A. D., Keynan, N. Y., Kratter, I. H., & Williams, N. (2024) · npj Mental Health Research · doi:10.1038/s44184-024-00099-2 · Cited by 8
“…other treatments (e.g. treatmentasusual)andmayhelptoidentifyif,inagiventimespan,theSNT processitself,regardlessofstimulation,leadstomoreimprovementinlas-situdethanothertreatments. rTMSdoesnotonlyproducelocalizedeffects;rather,bystimulating oneregionitcanhaveeffectsoninterconnectedbrainnetworks 34 .”
Gann, M. A., Paparella, I., Zich, C., Grigoras, I., Huertas‐Penen, S., Rieger, S. W., Thielscher, A., Sharott, A., Stagg, C. J., & Schwab, B. C. (2025) · Brain stimulation · doi:10.1016/j.brs.2025.08.011 · Cited by 7
Yuan, Y., Wu, Q., Wang, X., Liu, M., Yan, J., & Ji, H. (2023) · NeuroImage · doi:10.1016/j.neuroimage.2023.119979 · Cited by 8
Shao, H., Gu, G., Guo, X., Li, X., & Cui, D. Y. (2025) · Computer Methods and Programs in Biomedicine · doi:10.1016/j.cmpb.2025.108675 · Cited by 7
Buard, I., Lopez‐Esquibel, N., Schoeneberger, S., Berliner, J. M., & Kluger, B. M. (2020) · Cognitive and Behavioral Neurology · doi:10.1097/wnn.0000000000000224 · Cited by 7
Gupta, A. K., Kumar, A., & Chandrashekhar, N. (2021) · Industrial Psychiatry Journal · doi:10.4103/0972-6748.328795 · Cited by 7
“© 2021 Industrial Psychiatry Journal | Published by Wolters Kluwer - Medknow S93 session.[4-8] Many studies have suggested that rTMS could be efficacious in the treatment of major depression and other psychiatric indications.”
BackgroundLuckhardt, C., Schütz, M., Mühlherr, A. M., Boxhoorn, S., Ecker, C., Mössinger, H., Siemann, J., Schlechter, F., Castelo-Branco, M. S., Pereira, H. C., et al. (2025) · Autism Research · doi:10.1002/aur.70084 · Cited by 6
“It modulates cortical excitability, resulting in changes of resting state activity (Boonstra et al. 2016) and functional connectivity of brain networks (To et al. 2018).”
Zheng, Y., Tang, S., Zheng, H., Wang, X., Liu, L., Yang, Y., Zhen, Y., & Zheng, Z. (2023) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1010866 · Cited by 6
Konicar, L., Prillinger, K., Klöbl, M., Lanzenberger, R. R., Antal, A., & Plener, P. L. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.840836 · Cited by 7
“tDCS is also able to alter brain connectivity and thus likely modulate neural communication (32).”
BackgroundCochlear implant induced changes in cortical networks associated with tinnitus severity
Shoushtarian, M., Esmaelpoor, J., Bravo, M., & Fallon, J. B. (2024) · Journal of Neural Engineering · doi:10.1088/1741-2552/ad731d · Cited by 5
“To et al reported on evidence from studies on tinnitus and major depression showing effectiveness of neuromodulation techniques targeting the dorsolateral prefrontal cortex for both these conditions [31].”
Cortical waves and post‐stroke brain stimulation
Bessonov, N., Beuter, A. C., Trofimchuk, S. I., & Volpert, V. A. (2019) · Mathematical Methods in the Applied Sciences · doi:10.1002/mma.5620 · Cited by 5
Searchfield, G. D., Adhia, D. B., Barde, A., Ridder, D. D., Doborjeh, M., Doborjeh, Z., Goodey, R., Maslin, M. R. D., Sanders, P. J., Smith, P. F., et al. (2024) · Journal of the Royal Society of New Zealand · doi:10.1080/03036758.2024.2363424 · Cited by 5
“Further stimulation options include multisite electrical stimulation and bimodal stimulation (De Ridder and Vanneste 2014a; To et al. 2018; De Ridder, Adhia, et al. 2021).”
Bayat, F. K., Alp, M. İ., Bostan, S., Gülçür, H. Ö., Öztürk, G., & Güveniş, A. (2022) · European Biophysics Journal · doi:10.1007/s00249-022-01613-0 · Cited by 5
Ammanuel, S. G., Kondapavulur, S., Lu, A. Y., Breshears, J. D., Clark, J. P., Silva, A. B., & Chang, E. F. (2024) · Journal of neurosurgery · doi:10.3171/2023.10.jns231023 · Cited by 4
Beck, E. N., Narayanan, S. S., McDermott, R., & Witney, A. G. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/539510 · Cited by 5
“The DLPFC is a critical region for 109 cognitive and emotional processing, properties previously exploited with anodal tDCS to 110 modulate working memory (29,30), sustained attention (31), depression (32,33), and various 111 other processes in both healthy and patient populations (34).”
BackgroundGöke, K., McClintock, S. M., Mah, L., Rajji, T. K., Lee, H. H., Nestor, S. M., Downar, J., Noda, Y., Daskalakis, Z. J., Mulsant, B. H., et al. (2026) · The Canadian Journal of Psychiatry · doi:10.1177/07067437251315515 · Cited by 4
“…executive functions, such as response inhibition,set-shifting,andplanning. rTMSusesfocusedmag-netic fi eld pulses to modify neural activity at the stimulation site and can induce structural and functional connectivity changes in distributed brain networks, 14 including the cognitive control network.”
Li, L., Luo, X., Liu, Y., Jiang, Y., Chen, Y., Chen, Y., & Wang, J. (2025) · Neurology and Therapy · doi:10.1007/s40120-025-00759-1 · Cited by 4
“While M1-rTMS primarily modulated thalamocortical connectivity (Δ functional magnetic resonance imaging [fMRI] + 0.28; p < 0.001) [77, 78], pcTBS exhibited GABAergic plasticity enhancement (ΔGABA/ creatine ratio magnetic resonance spectroscopy [MRS] + 15%; p = 0.007) [79].”
InfluentialWickens, S., Gummersall, T., & Brown, T. (2025) · Brain and Cognition · doi:10.1016/j.bandc.2025.106307 · Cited by 4
Objective assessment of tinnitus laterality
Shoushtarian, M., Esmaelpoor, J., Bravo, M., & Fallon, J. B. (2025) · PLoS ONE · doi:10.1371/journal.pone.0325903 · Cited by 4
“As an example, in most neuromodulation studies for tinnitus where techniques such as transcranial magnetic stimulation are used, the left auditory cortex or dorsolateral prefrontal cortex (DLPFC) are targeted [2].”
Brazilian research on noninvasive brain stimulation applied to health conditions
Sá, K. N., Santos, G. V., de Souza, M. P., de Andrade, D. C., & Baptista, A. F. (2021) · Arquivos de Neuro-Psiquiatria · doi:10.1590/0004-282x-anp-2020-0480 · Cited by 4
Virtual neural network-guided optimization of non-invasive brain stimulation in Alzheimer’s disease
Luppi, J. J., Stam, C. J., Scheltens, P., & de Haan, W. (2024) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1011164 · Cited by 4
“Improvement of cognitive symptoms is presumably achieved by modulating pre-existing activity of specific parts of the brain, which in turn can exert influence on connected, unstimulated regions [20, 21].”
BackgroundCicero, N. G., Riley, E., Swallow, K. M., Rosa, E. D., & Anderson, A. K. (2025) · GeroScience · doi:10.1007/s11357-025-01582-0 · Cited by 4
“Neuromodulation techniques may be efficacious by targeting brain networks rather than just the focal region receiving stimulation [40–42].”
Bansal, K., Cattaneo, Z., Oldrati, V., Ferrari, C., Grossman, E. D., & Garcia, J. O. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.09.12.612716 · Cited by 4
“Neuromodulation has the potential to induce prolonged intervals of altered cortical dynamics between functionally connected circuits (Edwards et al., 2019; To et al., 2018).”
BackgroundMa, R., Wang, S., Yin, Z., Gan, Y., Zhao, Z., Yuan, T., Chen, Y., Du, T., Voon, V., Zhu, G., et al. (2026) · Journal of Psychiatry and Neuroscience · doi:10.1139/jpn-24-0163 · Cited by 3
Prabhu, N. M., Lehmann, N., Kaminski, E., Müller, N. G., & Taubert, M. (2024) · Scientific Reports · doi:10.1038/s41598-024-70857-x · Cited by 3
“The prefrontal networks that support the strategy building aspect of motor learning were the prime targets of c-tDCS in our study 24,46 .”
BackgroundMethodYadav, S., Sharma, S., Chatterjee, S., Sharma, A., & Thakur, S. (2025) · Lasers in Medical Science · doi:10.1007/s10103-025-04289-y · Cited by 3
“Additionally, LASER emission indirectly provides pain relief by stimu - lating the release of endogenous opioid peptides, acting as an analgesic by blocking pain signals carried by A-delta and C-fiber nerves [ 23, 45 –47 ].”
Antal, A., Ramasawmy, P., Rubal‐Otero, L., Chakalov, I., Rodríguez, M. Á., Hunold, A., Schellhorn, K., & Carrillo‐de‐la‐Peña, M. T. (2025) · BMC Cancer · doi:10.1186/s12885-025-15143-3 · Cited by 2
“Repeated anodal tDCS of M1 mediates analgesia both through local and network effects in the brain, employing long-lasting neuroplastic modifications that outlast the stimulation period [108–110].”
Jacob, R., Otto, A., Jarvers, I., Kandsperger, S., Ecker, A., Schleicher, D., Malloni, W. M., Neumann, I. D., & Brunner, R. M. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-07689-0 · Cited by 2
“Such findings could inform the refinement of neuromodulation techniques such as Transcranial Magnetic Stimulation or neurofeedback [21, 100], by targeting brain regions or connectivity profiles associated with impaired stress responses.”
Yadav, S., Sharma, S., Thakur, S. S., & Pattnaik, S. (2026) · Lasers in Medical Science · doi:10.1007/s10103-025-04778-0 · Cited by 2
“Additionally, LASER emission indirectly relieves pain by inducing the release of endogenous opioid peptides, which function as analgesics by blocking pain signals transmitted by A-delta and C-fibre nerves [ 2 , 20 –22].”
Bittencourt, A. M. L., FAVERO, B. P., Haas, C., Portolan, E. T., Gallardo, E., Rothmann, L. M., Grassi‐Oliveira, R., & Viola, T. W. (2026) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2026.113064 · Cited by 2
Contò, F., Agosta, S., Tadin, D., Pascual‐Leone, Á., & Battelli, L. (2026) · International Review of Psychiatry · doi:10.1080/09540261.2026.2677894 · Cited by 2
“These findings reinforce the view that noninvasive stimulation often exerts its influence through distributed networks rather than solely at the stimulation target (Cambiaghi, 2023; Contò et al., 2021; To et al., 2018).”
Quantifying test-retest reliability of repeated objective attentional measures in Lewy body dementia
Elder, G. J., Colloby, S. J., Firbank, M., & Taylor, J. (2022) · Journal of Neurology · doi:10.1007/s00415-022-10977-4 · Cited by 2
“Although attentional measures were not the primary outcome measure in the intervention group, tDCS may affect brain networks beyond the targeted localised region of interest [39].”
BackgroundCiricugno, A., Slaby, R. J., Benedek, M., & Cattaneo, Z. (2023) · Current clinical neurology · doi:10.1007/978-3-031-14724-1_7 · Cited by 3
Metadata
- Authors
- To, W. T., De Ridder, D., Hart Jr., J., & Vanneste, S.
- Affiliations
- The University of Texas at Dallas (US)
- Corresponding author
- To, Wing Ting
- Venue
- Frontiers in Human Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2018-04-13
- Volume
- 12
- Pages
- 128-128
- ISSN
- 1662-5161 (ISSN-L)
- PMC
- PMC5908883
- OpenAlex
- W2797266467
- Cited by
- 135
- References
- 237
- Citations by year
- 2026: 11 · 2025: 27 · 2024: 27 · 2023: 8 · 2022: 13 · 2021: 16 · 2020: 14 · 2019: 10 · 2018: 9
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Human Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
- Health Sciences › Medicine › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- non-invasive neuromodulation, repetitive transcranial magnetic stimulation, transcranial direct current stimulation, brain networks, tinnitus, major depressive disorder, dorsolateral prefrontal cortex, brain network connectivity, stimulation site selection
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