Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Non-invasive brain stimulation: current and future applications in neurology

Nature Reviews Neurology volume 21, pages 669–686 (2025)Cite this article

Subjects

Abstract

Device-based non-invasive brain stimulation (NIBS) techniques show promise for the treatment of neurological and psychiatric disorders, although inconsistencies in protocol designs and study findings can make the field difficult to navigate. In this Review, we discuss applications of NIBS for enhancing cognitive and motor function in people with various neurological diseases that are characterized by disruption of large-scale brain networks, including neurodegenerative diseases and brain lesion disorders such as stroke and traumatic brain injury. In particular, we focus on repetitive transcranial magnetic stimulation and transcranial electrical stimulation, as these techniques have been widely used in clinical settings and randomized controlled trials. We summarize and synthesize current knowledge, and highlight gaps and shortcomings in the existing research that make it difficult to draw firm conclusions, including small sample sizes, heterogeneous patient populations and variations in stimulation protocols. We believe that a rapid evolution of NIBS techniques from state-dependent, network-informed, multifocal and subcortical paradigms to individualized electric field modelling and accelerated NIBS protocols will improve the management of neurological disorders. However, realizing this potential will require us to address crucial challenges and acquire deeper mechanistic insights, with the aim of developing adaptive, biomarker-driven protocols to optimize target engagement, dosing and timing for each patient.

Key points

  • Repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), are the most commonly used non-invasive brain stimulation (NIBS) techniques to enhance motor and cognitive functions, facilitate adaptation to deficits and promote recovery in people with neurological disorders. New technological developments are allowing non-invasive stimulation of deep brain structures.

  • In Alzheimer disease, rTMS and tES typically target either the dorsolateral prefrontal cortex or hubs of the default-mode network (for example, the precuneus). Accelerated rTMS protocols are feasible and well tolerated, producing clinically meaningful cognitive benefits.

  • In Parkinson disease, evidence is limited by the narrow range of stimulation targets, small sample sizes, heterogeneity of patient cohorts and effects of dopaminergic medication. Proof-of-concept work highlights the auditory feedback area as a target for home-based treatment for hypokinetic dysarthria.

  • In stroke, neuromodulation approaches such as TMS and tES target various cortical hubs of the motor network, including the primary and secondary motor cortices. The effects are heterogeneous, and targeting of multiple cortical or core deep structures of the motor circuitries might achieve larger, more homogeneous treatment effects.

  • In traumatic brain injury, the left dorsolateral prefrontal cortex is a key target for tDCS or rTMS to enhance cognitive function. However, evidence is limited by study heterogeneity and small sample sizes, and large-scale controlled trials are warranted to establish efficacy.

  • The rapid evolution of NIBS techniques from state-dependent, network-informed, multifocal and subcortical paradigms to individualized electric field modelling and accelerated NIBS protocols holds great promise to improve the management of neurological disorders.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Non-invasive brain stimulation methods.
Fig. 2: Overview of the most widely used non-invasive brain stimulation techniques.
Fig. 3: Brain stimulation targets in Alzheimer disease and stroke.

Similar content being viewed by others

References

  1. Boon, P. et al. A strategic neurological research agenda for Europe: towards clinically relevant and patient-centred neurological research priorities. Eur. J. Neurol. 31, e16171 (2024).

    Article  PubMed  Google Scholar 

  2. Seeley, W. W., Crawford, R. K., Zhou, J., Miller, B. L. & Greicius, M. D. Neurodegenerative diseases target large-scale human brain networks. Neuron 62, 42–52 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Stam, C. J. Hub overload and failure as a final common pathway in neurological brain network disorders. Netw. Neurosci. 8, 1–23 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Murphy, K. R. et al. A practical guide to transcranial ultrasonic stimulation from the IFCN-endorsed ITRUSST consortium. Clin. Neurophysiol. 171, 192–226 (2025).

    Article  PubMed  Google Scholar 

  5. Violante, I. R. et al. Non-invasive temporal interference electrical stimulation of the human hippocampus. Nat. Neurosci. 26, 1994–2004 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wessel, M. J. et al. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nat. Neurosci. 26, 2005–2016 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Vassiliadis, P. et al. Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills. Nat. Hum. Behav. 8, 1581–1598 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Beanato, E. et al. Noninvasive modulation of the hippocampal-entorhinal complex during spatial navigation in humans. Sci. Adv. 10, eado4103 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yang, C. et al. Transcranial temporal interference stimulation of the right globus pallidus in Parkinson’s disease. Mov. Disord. 40, 1061–1069 (2025).

    Article  PubMed  Google Scholar 

  10. Piao, Y. et al. Safety evaluation of employing temporal interference transcranial alternating current stimulation in human studies. Brain Sci. 12, 1194 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Vassiliadis, P. et al. Safety, tolerability and blinding efficiency of non-invasive deep transcranial temporal interference stimulation: first experience from more than 250 sessions. J. Neural Eng. 21, 024001 (2024).

    Article  Google Scholar 

  12. Bergmann, T. O., Karabanov, A., Hartwigsen, G., Thielscher, A. & Siebner, H. R. Combining non-invasive transcranial brain stimulation with neuroimaging and electrophysiology: current approaches and future perspectives. Neuroimage 140, 4–19 (2016).

    Article  PubMed  Google Scholar 

  13. Bradley, C., Nydam, A. S., Dux, P. E. & Mattingley, J. B. State-dependent effects of neural stimulation on brain function and cognition. Nat. Rev. Neurosci. 23, 459–475 (2022).

    Article  CAS  PubMed  Google Scholar 

  14. Hartz, S. M. et al. Assessing the clinical meaningfulness of slowing CDR-SB progression with disease-modifying therapies for Alzheimer’s disease. Alzheimers Dement. Transl. Res. Clin. Interv. 11, e70033 (2025).

    Article  Google Scholar 

  15. Wei, N. et al. Repetitive transcranial magnetic stimulation may be superior to drug therapy in the treatment of Alzheimer’s disease: a systematic review and Bayesian network meta-analysis. CNS Neurosci. Ther. 29, 2912–2924 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Koch, G. et al. The emerging field of non-invasive brain stimulation in Alzheimer’s disease. Brain 147, 4003–4016 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Terao, I. & Kodama, W. Comparative efficacy, tolerability and acceptability of donanemab, lecanemab, aducanumab and lithium on cognitive function in mild cognitive impairment and Alzheimer’s disease: a systematic review and network meta-analysis. Ageing Res. Rev. 94, 102203 (2024).

    Article  CAS  PubMed  Google Scholar 

  18. Šimko, P., Kent, J. A. & Rektorova, I. Is non-invasive brain stimulation effective for cognitive enhancement in Alzheimer’s disease? An updated meta-analysis. Clin. Neurophysiol. 144, 23–40 (2022).

    Article  PubMed  Google Scholar 

  19. Yang, T. et al. The cognitive effect of non-invasive brain stimulation combined with cognitive training in Alzheimer’s disease and mild cognitive impairment: a systematic review and meta-analysis. Alzheimers Res. Ther. 16, 140 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rektorová, I. Non-invasive stimulation for treating cognitive impairment in Alzheimer disease. Nat. Rev. Neurol. 20, 445–446 (2024).

    Article  PubMed  Google Scholar 

  21. Moussavi, Z. et al. Repetitive transcranial magnetic stimulation as a treatment for Alzheimer’s disease: a randomized placebo-controlled double-blind clinical trial. Neurotherapeutics 21, e00331 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Lin, H. et al. Effects of accelerated intermittent theta-burst stimulation in modulating brain of Alzheimer’s disease. Cereb. Cortex 34, bhae106 (2024).

    Article  PubMed  Google Scholar 

  23. Wu, X. et al. Accelerated intermittent theta-burst stimulation broadly ameliorates symptoms and cognition in Alzheimer’s disease: a randomized controlled trial. Brain Stimul. 15, 35–45 (2022).

    Article  PubMed  Google Scholar 

  24. Tang, N., Shu, W. & Wang, H.-N. Accelerated transcranial magnetic stimulation for major depressive disorder: a quick path to relief? Wiley Interdiscip. Rev. Cogn. Sci. 15, e1666 (2024).

    Article  PubMed  Google Scholar 

  25. Wu, X. et al. Effects of a periodic intermittent theta burst stimulation in Alzheimer’s disease. Gen. Psychiatr. 37, e101106 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  26. Jones, D. T. et al. Cascading network failure across the Alzheimer’s disease spectrum. Brain 139, 547–562 (2016).

    Article  PubMed  Google Scholar 

  27. Giorgio, J., Adams, J. N., Maass, A., Jagust, W. J. & Breakspear, M. Amyloid induced hyperexcitability in default mode network drives medial temporal hyperactivity and early tau accumulation. Neuron 112, 676–686.e4 (2024).

    Article  CAS  PubMed  Google Scholar 

  28. Krajcovicova, L., Marecek, R., Mikl, M. & Rektorova, I. Disruption of resting functional connectivity in Alzheimer’s patients and at-risk Subjects. Curr. Neurol. Neurosci. Rep. 14, 491 (2014).

    Article  PubMed  Google Scholar 

  29. Koch, G. et al. Transcranial magnetic stimulation of the precuneus enhances memory and neural activity in prodromal Alzheimer’s disease. Neuroimage 169, 302–311 (2018).

    Article  PubMed  Google Scholar 

  30. Koch, G. et al. Precuneus magnetic stimulation for Alzheimer’s disease: a randomized, sham-controlled trial. Brain 145, 3776–3786 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  31. Yao, Q. et al. Effect of cerebellum stimulation on cognitive recovery in patients with Alzheimer disease: a randomized clinical trial. Brain Stimul. 15, 910–920 (2022).

    Article  PubMed  Google Scholar 

  32. Chen, Y. et al. Integrated cerebellar radiomic-network model for predicting mild cognitive impairment in Alzheimer’s disease. Alzheimers Dement. 21, e14361 (2025).

    Article  CAS  PubMed  Google Scholar 

  33. Majdi, A., van Boekholdt, L., Sadigh-Eteghad, S. & Mc Laughlin, M. A systematic review and meta-analysis of transcranial direct-current stimulation effects on cognitive function in patients with Alzheimer’s disease. Mol. Psychiatry 27, 2000–2009 (2022).

    Article  CAS  PubMed  Google Scholar 

  34. Huo, L. et al. Effects of transcranial direct current stimulation on episodic memory in older adults: a meta-analysis. J. Gerontol. B 76, 692–702 (2021).

    Article  Google Scholar 

  35. Rezakhani, S., Amiri, M., Hassani, A., Esmaeilpour, K. & Sheibani, V. Anodal HD-tDCS on the dominant anterior temporal lobe and dorsolateral prefrontal cortex: clinical results in patients with mild cognitive impairment. Alzheimers Res. Ther. 16, 27 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Šimko, P. et al. Exploring the impact of intensified multiple session tDCS over the left DLPFC on brain function in MCI: a randomized control trial. Sci. Rep. 14, 1512 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  37. Im, J. J. et al. Effects of 6-month at-home transcranial direct current stimulation on cognition and cerebral glucose metabolism in Alzheimer’s disease. Brain Stimul. 12, 1222–1228 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Agboada, D., Mosayebi-Samani, M., Kuo, M. F. & Nitsche, M. A. Induction of long-term potentiation-like plasticity in the primary motor cortex with repeated anodal transcranial direct current stimulation — better effects with intensified protocols? Brain Stimul. 13, 987–997 (2020).

    Article  PubMed  Google Scholar 

  39. Nissim, N. R. et al. Efficacy of transcranial alternating current stimulation in the enhancement of working memory performance in healthy adults: a systematic meta-analysis. Neuromodulation 26, 728–737 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Manippa, V. et al. Cognitive and neuropathophysiological outcomes of gamma-tACS in dementia: a systematic review. Neuropsychol. Rev. 34, 338–361 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  41. Jafari, Z., Kolb, B. E. & Mohajerani, M. H. Neural oscillations and brain stimulation in Alzheimer’s disease. Prog. Neurobiol. 194, 101878 (2020).

    Article  CAS  PubMed  Google Scholar 

  42. Gillespie, A. K. et al. Apolipoprotein E4 causes age-dependent disruption of slow gamma oscillations during hippocampal sharp-wave ripples. Neuron 90, 740–751 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Babiloni, C. et al. Brain neural synchronization and functional coupling in Alzheimer’s disease as revealed by resting state EEG rhythms. Int. J. Psychophysiol. 103, 88–102 (2016).

    Article  PubMed  Google Scholar 

  44. Benussi, A. et al. Exposure to gamma tACS in Alzheimer’s disease: a randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimul. 14, 531–540 (2021).

    Article  PubMed  Google Scholar 

  45. Benussi, A. et al. Increasing brain gamma activity improves episodic memory and restores cholinergic dysfunction in Alzheimer’s disease. Ann. Neurol. 92, 322–334 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Chan, D. et al. Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: results of feasibility and pilot studies. PLoS ONE 17, e0278412 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Jung, Y. H. et al. Effectiveness of personalized hippocampal network–targeted stimulation in Alzheimer disease. JAMA Netw. Open 7, e249220 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Pupíková, M. et al. Physiology-inspired bifocal fronto-parietal tACS for working memory enhancement. Heliyon 10, e37427 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  49. Anderkova, L., Eliasova, I., Marecek, R., Janousova, E. & Rektorova, I. Distinct pattern of gray matter atrophy in mild Alzheimer’s disease impacts on cognitive outcomes of noninvasive brain stimulation. J. Alzheimers Dis. 48, 251–260 (2015).

    Article  PubMed  Google Scholar 

  50. Altomare, D. et al. Home-based transcranial alternating current stimulation (tACS) in Alzheimer’s disease: rationale and study design. Alzheimers Res. Ther. 15, 155 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  51. Benussi, A. et al. Alpha tACS improves cognition and modulates neurotransmission in dementia with Lewy bodies. Mov. Disord. 39, 1993–2003 (2024).

    Article  CAS  PubMed  Google Scholar 

  52. Grossman, M. et al. Frontotemporal lobar degeneration. Nat. Rev. Dis. Primers 9, 40 (2023).

    Article  PubMed  Google Scholar 

  53. Roheger, M. et al. Non-pharmacological interventions for improving language and communication in people with primary progressive aphasia. Cochrane Database Syst. Rev. 5, CD015067 (2024).

    PubMed  Google Scholar 

  54. Lamoš, M., Morávková, I., Ondráček, D., Bočková, M. & Rektorová, I. Altered spatiotemporal dynamics of the resting brain in mild cognitive impairment with Lewy bodies. Mov. Disord. 36, 2435–2440 (2021).

    Article  PubMed  Google Scholar 

  55. Bonakdarpour, B. et al. Perturbations of language network connectivity in primary progressive aphasia. Cortex 121, 468–480 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  56. Zhou, J. et al. Divergent network connectivity changes in behavioural variant frontotemporal dementia and Alzheimer’s disease. Brain 133, 1352–1367 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  57. Höglinger, G. U. et al. A biological classification of Parkinson’s disease: the SynNeurGe research diagnostic criteria. Lancet Neurol. 23, 191–204 (2024).

    Article  PubMed  Google Scholar 

  58. Simuni, T. et al. A biological definition of neuronal α-synuclein disease: towards an integrated staging system for research. Lancet Neurol. 23, 178–190 (2024).

    Article  CAS  PubMed  Google Scholar 

  59. Rektorova, I. Current treatment of behavioral and cognitive symptoms of Parkinson’s disease. Parkinsonism Relat. Disord. 59, 65–73 (2019).

    Article  PubMed  Google Scholar 

  60. Brabenec, L., Mekyska, J., Galaz, Z. & Rektorova, I. Speech disorders in Parkinson’s disease: early diagnostics and effects of medication and brain stimulation. J. Neural Transm. 124, 303–334 (2017).

    Article  CAS  PubMed  Google Scholar 

  61. Rektorova, I., Barrett, J., Mikl, M., Rektor, I. & Paus, T. Functional abnormalities in the primary orofacial sensorimotor cortex during speech in Parkinson’s disease. Mov. Disord. 22, 2043–2051 (2007).

    Article  PubMed  Google Scholar 

  62. Brabenec, L., Simko, P., Sejnoha Minsterova, A., Kostalova, M. & Rektorova, I. Repetitive transcranial magnetic stimulation for hypokinetic dysarthria in Parkinson’s disease enhances white matter integrity of the auditory–motor loop. Eur. J. Neurol. 30, 881–886 (2023).

    Article  PubMed  Google Scholar 

  63. Klobusiakova, P. et al. Articulatory network reorganization in Parkinson’s disease as assessed by multimodal MRI and acoustic measures. Parkinsonism Relat. Disord. 84, 122–128 (2021).

    Article  PubMed  Google Scholar 

  64. Brabenec, L. et al. Non-invasive stimulation of the auditory feedback area for improved articulation in Parkinson’s disease. Parkinsonism Relat. Disord. 61, 187–192 (2019).

    Article  PubMed  Google Scholar 

  65. Brabenec, L. et al. Non-invasive brain stimulation for speech in Parkinson’s disease: a randomized controlled trial. Brain Stimul. 14, 571–578 (2021).

    Article  PubMed  Google Scholar 

  66. Brabenec, L. et al. Short-term effects of transcranial direct current stimulation on motor speech in Parkinson’s disease: a pilot study. J. Neural Transm. 131, 791–797 (2024).

    Article  PubMed  Google Scholar 

  67. Aarsland, D., Brønnick, K., Larsen, J. P., Tysnes, O. B. & Alves, G. Cognitive impairment in incident, untreated Parkinson disease: the Norwegian ParkWest study. Neurology 72, 1121–1126 (2009).

    Article  CAS  PubMed  Google Scholar 

  68. Litvan, I. et al. Diagnostic criteria for mild cognitive impairment in Parkinson’s disease: movement disorder society task force guidelines. Mov. Disord. 27, 349–356 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Giustiniani, A., Maistrello, L., Mologni, V., Danesin, L. & Burgio, F. TMS and tDCS as potential tools for the treatment of cognitive deficits in Parkinson’s disease: a meta-analysis. Neurol. Sci. 46, 579–592 (2025).

    Article  PubMed  Google Scholar 

  70. Pupíková, M. & Rektorová, I. Non-pharmacological management of cognitive impairment in Parkinson’s disease. J. Neural Transm. 127, 799–820 (2020).

    Article  PubMed  Google Scholar 

  71. Lee, H., Choi, B. J. & Kang, N. Non-invasive brain stimulation enhances motor and cognitive performances during dual tasks in patients with Parkinson’s disease: a systematic review and meta-analysis. J. Neuroeng. Rehabil. 21, 205 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  72. Duan, Z. & Zhang, C. Transcranial direct current stimulation for Parkinson’s disease: systematic review and meta-analysis of motor and cognitive effects. npj Parkinsons Dis. 10, 214 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  73. He, W., Wang, J.-C. & Tsai, P.-Y. Theta burst magnetic stimulation improves Parkinson’s-related cognitive impairment: a randomised controlled study. Neurorehabil. Neural Repair 35, 986–995 (2021).

    Article  PubMed  Google Scholar 

  74. Buard, I. et al. Transcranial magnetic stimulation does not improve mild cognitive impairment in Parkinson’s disease. Mov. Disord. 33, 489–491 (2018).

    Article  PubMed  Google Scholar 

  75. Del Felice, A. et al. Personalized transcranial alternating current stimulation (tACS) and physical therapy to treat motor and cognitive symptoms in Parkinson’s disease: a randomized cross-over trial. Neuroimage Clin. 22, 101768 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Wei, W. et al. Acute improvement in the attention network with repetitive transcranial magnetic stimulation in Parkinson’s disease. Disabil. Rehabil. 44, 7958–7966 (2022).

    Article  PubMed  Google Scholar 

  77. Pal, E., Nagy, F., Aschermann, Z., Balazs, E. & Kovacs, N. The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson’s disease: a randomized, double-blind, placebo-controlled study. Mov. Disord. 25, 2311–2317 (2010).

    Article  PubMed  Google Scholar 

  78. Aksu, S. et al. Does transcranial direct current stimulation enhance cognitive performance in Parkinson’s disease mild cognitive impairment? An event-related potentials and neuropsychological assessment study. Neurol. Sci. 43, 4029–4044 (2022).

    Article  PubMed  Google Scholar 

  79. Chung, C. L., Mak, M. K. & Hallett, M. Transcranial magnetic stimulation promotes gait training in Parkinson disease. Ann. Neurol. 88, 933–945 (2020).

    Article  PubMed  Google Scholar 

  80. Wong, P.-L., Yang, Y.-R., Huang, S.-F. & Wang, R.-Y. Effects of DLPFC tDCS followed by treadmill training on dual-task gait and cortical excitability in Parkinson’s disease: a randomized controlled trial. Neurorehabil. Neural Repair 38, 680–692 (2024).

    Article  PubMed  Google Scholar 

  81. Rufener, K. S., Oechslin, M. S., Zaehle, T. & Meyer, M. Transcranial alternating current stimulation (tACS) differentially modulates speech perception in young and older adults. Brain Stimul. 9, 560–565 (2016).

    Article  PubMed  Google Scholar 

  82. Nemcova Elfmarkova, N., Gajdos, M., Rektorova, I., Marecek, R. & Rapcsak, S. Z. Neural evidence for defective top-down control of visual processing in Parkinson’s and Alzheimer’s disease. Neuropsychologia 106, 236–244 (2017).

    Article  PubMed  Google Scholar 

  83. Rucco, R. et al. Brain networks and cognitive impairment in Parkinson’s disease. Brain Connect. 12, 465–475 (2022).

    Article  PubMed  Google Scholar 

  84. Srovnalova, H., Marecek, R. & Rektorova, I. The role of the inferior frontal gyri in cognitive processing of patients with Parkinson’s disease: a pilot rTMS study. Mov. Disord. 26, 1545–1548 (2011).

    Article  PubMed  Google Scholar 

  85. Monastero, R. et al. Transcranial random noise stimulation over the primary motor cortex in PD-MCI patients: a crossover, randomized, sham-controlled study. J. Neural Transm. 127, 1589–1597 (2020).

    Article  PubMed  Google Scholar 

  86. Madrid, J. & Benninger, D. H. Non-invasive brain stimulation for Parkinson’s disease: clinical evidence, latest concepts and future goals: a systematic review. J. Neurosci. Methods 347, 108957 (2021).

    Article  PubMed  Google Scholar 

  87. Monte-Silva, K., Liebetanz, D., Grundey, J., Paulus, W. & Nitsche, M. A. Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity. J. Physiol. 588, 3415–3424 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Zhang, W. et al. Efficacy of repetitive transcranial magnetic stimulation in Parkinson’s disease: a systematic review and meta-analysis of randomised controlled trials. EClinicalMedicine 52, 101589 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Li, R. et al. Effects of repetitive transcranial magnetic stimulation on motor symptoms in Parkinson’s disease: a meta-analysis. Neurorehabil. Neural Repair 36, 395–404 (2022).

    Article  PubMed  Google Scholar 

  90. Goodwill, A. M. et al. Using non-invasive transcranial stimulation to improve motor and cognitive function in Parkinson’s disease: a systematic review and meta-analysis. Sci. Rep. 7, 14840 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  91. Pereira, J. B. et al. Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson’s disease. Brain Stimul. 6, 16–24 (2013).

    Article  PubMed  Google Scholar 

  92. Manenti, R. et al. Transcranial direct current stimulation combined with cognitive training for the treatment of Parkinson disease: a randomized, placebo-controlled study. Brain Stimul. 11, 1251–1262 (2018).

    Article  PubMed  Google Scholar 

  93. Cools, R. Dopaminergic modulation of cognitive function-implications for l-DOPA treatment in Parkinson’s disease. Neurosci. Biobehav. Rev. 30, 1–23 (2006).

    Article  CAS  PubMed  Google Scholar 

  94. GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet Psychiatry 9, 137–150 (2022).

    Article  PubMed Central  Google Scholar 

  95. Ponsford, J. L. et al. Longitudinal follow-up of patients with traumatic brain injury: outcome at two, five, and ten years post-injury. J. Neurotrauma 31, 64–77 (2014).

    Article  PubMed  Google Scholar 

  96. Feigin, V. L. et al. Pragmatic solutions to reduce the global burden of stroke: a World Stroke Organization–Lancet Neurology Commission. Lancet Neurol. 22, 1160–1206 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  97. Marshall, S. et al. Updated clinical practice guidelines for concussion/mild traumatic brain injury and persistent symptoms. Brain Inj. 29, 688–700 (2015).

    Article  PubMed  Google Scholar 

  98. Lefaucheur, J. P. et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): an update (2014–2018). Clin. Neurophysiol. 131, 474–528 (2020).

    Article  PubMed  Google Scholar 

  99. Antal, A. et al. Low intensity transcranial electric stimulation: safety, ethical, legal regulatory and application guidelines. Clin. Neurophysiol. 128, 1774–1809 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Murase, N., Duque, J., Mazzocchio, R. & Cohen, L. G. Influence of interhemispheric interactions on motor function in chronic stroke. Ann. Neurol. 55, 400–409 (2004).

    Article  PubMed  Google Scholar 

  101. Morishita, T. & Hummel, F. C. Non-invasive brain stimulation (NIBS) in motor recovery after stroke: concepts to increase efficacy. Curr. Behav. Neurosci. Rep. 4, 280–289 (2017).

    Article  Google Scholar 

  102. Coscia, M. et al. Neurotechnology-aided interventions for upper limb motor rehabilitation in severe chronic stroke. Brain 142, 2182–2197 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Safdar, A., Smith, M. C., Byblow, W. D. & Stinear, C. M. Applications of repetitive transcranial magnetic stimulation to improve upper limb motor performance after stroke: a systematic review. Neurorehabil. Neural Repair 37, 837–849 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  104. Savelon, E. C. J., Jordan, H. T., Stinear, C. M. & Byblow, W. D. Noninvasive brain stimulation to improve motor outcomes after stroke. Curr. Opin. Neurol. 37, 621–628 (2024).

    Article  PubMed  Google Scholar 

  105. Bornheim, S., Croisier, J. L., Maquet, P. & Kaux, J. F. Transcranial direct current stimulation associated with physical-therapy in acute stroke patients — a randomized, triple blind, sham-controlled study. Brain Stimul. 13, 329–336 (2020).

    Article  PubMed  Google Scholar 

  106. Garrido, M. M. et al. Early transcranial direct current stimulation with modified constraint-induced movement therapy for motor and functional upper limb recovery in hospitalized patients with stroke: a randomized, multicentre, double-blind, clinical trial. Brain Stimul. 16, 40–47 (2023).

    Article  Google Scholar 

  107. Cordes, D. et al. Efficacy and safety of transcranial direct current stimulation to the ipsilesional motor cortex in subacute stroke (NETS): a multicenter, randomized, double-blind, placebo-controlled trial. Lancet Reg. Health Eur. 38, 100825 (2024).

    Article  Google Scholar 

  108. Schlaug, G. et al. Safety and efficacy of transcranial direct current stimulation in addition to constraint-induced movement therapy for post-stroke motor recovery (TRANSPORT2): a phase 2, multicentre, randomised, sham-controlled triple-blind trial. Lancet Neurol. 24, 400–412 (2025).

    Article  PubMed  Google Scholar 

  109. Harvey, R. L. et al. Randomized sham-controlled trial of navigated repetitive transcranial magnetic stimulation for motor recovery in stroke the NICHE trial. Stroke 49, 2138–2146 (2018).

    Article  PubMed  Google Scholar 

  110. Luk, K. Y., Ouyang, H. X. & Pang, M. Y. C. Low-Frequency rTMS over contralesional M1 increases ipsilesional cortical excitability and motor function with decreased interhemispheric asymmetry in subacute stroke: a randomized controlled study. Neural Plast. 2022, 3815357 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  111. Ahmed, I., Yeldan, I. & Mustafaoglu, R. The adjunct of electric neurostimulation to rehabilitation approaches in upper limb stroke rehabilitation: a systematic review with network meta-analysis of randomized controlled trials. Neuromodulation 25, 1197–1214 (2022).

    Article  PubMed  Google Scholar 

  112. Hofmeijer, J., Ham, F. & Kwakkel, G. Evidence of rTMS for motor or cognitive stroke recovery: hype or hope? Stroke 54, 2500–2511 (2023).

    Article  PubMed  Google Scholar 

  113. Lu, J. et al. Effect of intermittent theta burst stimulation on upper limb function in stroke patients: a systematic review and meta-analysis. Front. Neurol. 15, 1450435 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Tang, Z. et al. Efficacy and safety of high-dose TBS on poststroke upper extremity motor impairment: a randomized controlled trial. Stroke 55, 2212–2220 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Bian, L. et al. Effects of priming intermittent theta burst stimulation with high-definition tDCS on upper limb function in hemiparetic patients with stroke: a randomized controlled study. Neurorehabil. Neural Repair 38, 268–278 (2024).

    Article  PubMed  Google Scholar 

  116. Vink, J. J. T. et al. Continuous theta-burst stimulation of the contralesional primary motor cortex for promotion of upper limb recovery after stroke: a randomized controlled trial. Stroke 54, 1962–1971 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  117. Barker-Collo, S. & Feigin, V. The impact of neuropsychological deficits on functional stroke outcomes. Neuropsychol. Rev. 16, 53–64 (2006).

    Article  PubMed  Google Scholar 

  118. Milosevich, E. T., Moore, M. J., Pendlebury, S. T. & Demeyere, N. Domain-specific cognitive impairment 6 months after stroke: the value of early cognitive screening. Int. J. Stroke 19, 331–341 (2024).

    Article  PubMed  Google Scholar 

  119. Draaisma, L. R., Wessel, M. J. & Hummel, F. C. Non-invasive brain stimulation to enhance cognitive rehabilitation after stroke. Neurosci. Lett. 719, 133678 (2020).

    Article  CAS  PubMed  Google Scholar 

  120. Stockbridge, M. D. et al. Transcranial direct-current stimulation in subacute aphasia: a randomized controlled trial. Stroke 54, 912–920 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Jung, I.-Y., Lim, J. Y., Kang, E. K., Sohn, H. M. & Paik, N.-J. The factors associated with good responses to speech therapy combined with transcranial direct current stimulation in post-stroke aphasic patients. Ann. Rehabil. Med. 35, 460 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Ren, J. et al. Personalized functional imaging-guided rTMS on the superior frontal gyrus for post-stroke aphasia: a randomized sham-controlled trial. Brain Stimul. 16, 1313–1321 (2023).

    Article  PubMed  Google Scholar 

  123. Biou, E. et al. Transcranial direct current stimulation in post-stroke aphasia rehabilitation: a systematic review. Ann. Phys. Rehabil. Med. 62, 104–121 (2019).

    Article  PubMed  Google Scholar 

  124. Chai, L. et al. Does SLT combined with NIBS enhance naming recovery in post-stroke aphasia? A meta-analysis and systematic review. NeuroRehabilitation 54, 543–561 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Elsner, B., Kugler, J., Pohl, M. & Mehrholz, J. Transcranial direct current stimulation (tDCS) for improving aphasia in adults with aphasia after stroke. Cochrane Database Syst. Rev. 5, CD009760 (2019).

    PubMed  Google Scholar 

  126. Raymer, A. M. & Johnson, R. K. Effectiveness of transcranial direct current stimulation as an adjuvant to aphasia treatment following stroke: evidence from systematic reviews and meta-analyses. Am. J. Speech Lang. Pathol. 33, 3431–3443 (2024).

    Article  PubMed  Google Scholar 

  127. You, Y. et al. Long-term effects of transcranial direct current stimulation (tDCS) combined with speech language therapy (SLT) on post-stroke aphasia patients: a systematic review and network meta-analysis of randomized controlled trials. NeuroRehabilitation 53, 285–296 (2023).

    Article  PubMed  Google Scholar 

  128. Longley, V. et al. Non-pharmacological interventions for spatial neglect or inattention following stroke and other non-progressive brain injury. Cochrane Database Syst. Rev. 7, CD003586 (2021).

    PubMed  Google Scholar 

  129. Nyffeler, T. et al. Theta burst stimulation in neglect after stroke: functional outcome and response variability origins. Brain 142, 992–1008 (2019).

    Article  PubMed  Google Scholar 

  130. Lin, R. et al. Does repetitive transcranial magnetic stimulation have a beneficial effect on improving unilateral spatial neglect caused by stroke? A meta-analysis. J. Neurol. 271, 6494–6507 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  131. Wang, Y., Xu, N., Wang, R. & Zai, W. Systematic review and network meta-analysis of effects of noninvasive brain stimulation on post-stroke cognitive impairment. Front. Neurosci. 16, 1082383 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  132. Gong, C. et al. Therapeutic effects of repetitive transcranial magnetic stimulation on cognitive impairment in stroke patients: a systematic review and meta-analysis. Front. Hum. Neurosci. 17, 1177594 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  133. Li, Y. et al. The efficacy and safety of post-stroke cognitive impairment therapies: an umbrella review. Front. Pharmacol. 14, 1207075 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Li, W. et al. Improvement of poststroke cognitive impairment by intermittent theta bursts: a double-blind randomized controlled trial. Brain Behav. 12, e2569 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Liu, Y. et al. High-frequency rTMS broadly ameliorates working memory and cognitive symptoms in stroke patients: a randomized controlled trial. Neurorehabil. Neural Repair 38, 729–741 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Liu, Y. W. et al. Explore combined use of transcranial direct current stimulation and cognitive training on executive function after stroke. J. Rehabil. Med. 53, 2766 (2021).

    PubMed  PubMed Central  Google Scholar 

  137. Guggisberg, A. G., Koch, P. J., Hummel, F. C. & Buetefisch, C. M. Brain networks and their relevance for stroke rehabilitation. Clin. Neurophysiol. 130, 1098–1124 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Koch, P. J. et al. The structural connectome and motor recovery after stroke: predicting natural recovery. Brain 144, 2107–2119 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  139. Micera, S., Caleo, M., Chisari, C., Hummel, F. C. & Pedrocchi, A. Advanced neurotechnologies for the restoration of motor function. Neuron 105, 604–620 (2020).

    Article  CAS  PubMed  Google Scholar 

  140. Hummel, F. C. et al. Controversy: noninvasive and invasive cortical stimulation show efficacy in treating stroke patients. Brain Stimul. 1, 370–382 (2008).

    Article  PubMed  Google Scholar 

  141. Di Pino, G. et al. Modulation of brain plasticity in stroke: a novel model for neurorehabilitation. Nat. Rev. Neurol. 10, 597–608 (2014).

    Article  PubMed  Google Scholar 

  142. Maceira-Elvira, P. et al. Dissecting motor skill acquisition: spatial coordinates take precedence. Sci. Adv. 8, 3505 (2022).

    Article  Google Scholar 

  143. Maceira-Elvira, P. et al. Native learning ability and not age determines the effects of brain stimulation. npj Sci. Learn. 9, 69 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  144. Jiang, L. et al. Optogenetic inhibition of striatal GABAergic neuronal activity improves outcomes after ischemic brain injury. Stroke 48, 3375–3383 (2017).

    Article  CAS  PubMed  Google Scholar 

  145. Song, M. et al. Optogenetic stimulation of glutamatergic neuronal activity in the striatum enhances neurogenesis in the subventricular zone of normal and stroke mice. Neurobiol. Dis. 98, 9–24 (2017).

    Article  CAS  PubMed  Google Scholar 

  146. Proulx, C. E. & Hummel, F. C. Beyond the surface: advancing neurorehabilitation with transcranial temporal interference stimulation — clinical applications and future prospects. Neural Regen. Res. https://doi.org/10.4103/NRR.NRR-D-24-01573 (2025).

  147. Wessel, M. J. et al. Multi-focal stimulation of the cortico-cerebellar loop during the acquisition of a novel hand motor skill in chronic stroke survivors. Cerebellum 23, 341–354 (2024).

    Article  CAS  PubMed  Google Scholar 

  148. Wessel, M. J. et al. Multifocal stimulation of the cerebro-cerebellar loop during the acquisition of a novel motor skill. Sci. Rep. 11, 1756 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Bevilacqua, M. et al. Pathway-dependent brain stimulation responses indicate motion processing integrity after stroke. Brain 139, 16–17 (2025).

    Google Scholar 

  150. Bevilacqua, M. et al. Single session cross-frequency bifocal tACS modulates visual motion network activity in young healthy population and stroke patients. Brain Stimul. 17, 660–667 (2024).

    Article  PubMed  Google Scholar 

  151. Raffin E. B. M. et al. Boosting hemianopia recovery: the power of interareal cross-frequency brain stimulation. Brain (in the press).

  152. Arheix-Parras, S. et al. A systematic review of repetitive transcranial magnetic stimulation in aphasia rehabilitation: leads for future studies. Neurosci. Biobehav. Rev. 127, 212–241 (2021).

    Article  PubMed  Google Scholar 

  153. Wang, Y. et al. Comparative efficacy of different noninvasive brain stimulation therapies for recovery of global cognitive function, attention, memory, and executive function after stroke: a network meta-analysis of randomized controlled trials. Ther. Adv. Chronic Dis. 14, 20406223231168754 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  154. Grover, S., Fayzullina, R., Bullard, B. M., Levina, V. & Reinhart, R. M. G. A meta-analysis suggests that tACS improves cognition in healthy, aging, and psychiatric populations. Sci. Transl. Med. 15, eabo2044 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  155. Schuhmann, T. et al. Transcranial alternating brain stimulation at alpha frequency reduces hemispatial neglect symptoms in stroke patients. Int. J. Clin. Health Psychol. 22, 100326 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  156. Chen, J. et al. Efficacy of rTMS combined with cognitive training in TBI with cognition disorder: a systematic review and meta-analysis. Neurol. Sci. 45, 3683–3697 (2024).

    Article  PubMed  Google Scholar 

  157. Tsai, P. Y., Chen, Y. C., Wang, J. Y., Chung, K. H. & Lai, C. H. Effect of repetitive transcranial magnetic stimulation on depression and cognition in individuals with traumatic brain injury: a systematic review and meta-analysis. Sci. Rep. 11, 16940 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  158. Franke, L. M. et al. Randomized trial of rTMS in traumatic brain injury: improved subjective neurobehavioral symptoms and increases in EEG delta activity. Brain Inj. 36, 683–692 (2022).

    Article  PubMed  Google Scholar 

  159. Neville, I. S. et al. Repetitive TMS does not improve cognition in patients with TBI: a randomized double-blind trial. Neurology 93, E190–E199 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  160. Verisezan Rosu, O. et al. Cerebrolysin and repetitive transcranial magnetic stimulation (rTMS) in patients with traumatic brain injury: a three-arm randomized trial. Front. Neurosci. 17, 1186751 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Afsharipoor, M. et al. Combined transcranial direct current stimulation with occupational therapy improves activities of daily living in traumatic brain injuries: a pilot randomized clinical trial. J. Mod. Rehabil. 18, 114–120 (2024).

    Google Scholar 

  162. Motes, M. A. et al. High-definition transcranial direct current stimulation to improve verbal retrieval deficits in chronic traumatic brain injury. J. Neurotrauma 37, 170–177 (2020).

    Article  PubMed  Google Scholar 

  163. Quinn, D. K. et al. Transcranial direct current stimulation modulates working memory and prefrontal-insula connectivity after mild-moderate traumatic brain injury. Front. Hum. Neurosci. 16, 1026639 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  164. Sacco, K. et al. Concomitant use of transcranial direct current stimulation and computer-assisted training for the rehabilitation of attention in traumatic brain injured patients: behavioral and neuroimaging results. Front. Behav. Neurosci. 10, 57 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  165. Li, L. M. et al. Traumatic axonal injury influences the cognitive effect of non-invasive brain stimulation. Brain 142, 3280–3293 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  166. Chiang, H. S., Motes, M., Kraut, M., Vanneste, S. & Hart, J. High-definition transcranial direct current stimulation modulates theta response during a Go-NoGo task in traumatic brain injury. Clin. Neurophysiol. 143, 36–47 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  167. Galimberti, A., Tik, M., Pellegrino, G. & Schuler, A. L. Effectiveness of rTMS and tDCS treatment for chronic TBI symptoms: a systematic review and meta-analysis. Prog. Neuropsychopharmacol. Biol. Psychiatry 128, 110863 (2024).

    Article  CAS  PubMed  Google Scholar 

  168. Yang, Z. et al. Behavioral effects of repetitive transcranial magnetic stimulation in disorders of consciousness: a systematic review and meta-analysis. Brain Sci. 13, 1362 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  169. Hoy, K. E. et al. A pilot investigation of repetitive transcranial magnetic stimulation for post-traumatic brain injury depression: safety, tolerability, and efficacy. J. Neurotrauma 36, 2092–2098 (2019).

    Article  PubMed  Google Scholar 

  170. Kim, W. S., Lee, K., Kim, S., Cho, S. & Paik, N. J. Transcranial direct current stimulation for the treatment of motor impairment following traumatic brain injury. J. Neuroeng. Rehabil. 16, 14 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Surendrakumar, S. et al. Neuromodulation therapies in pre-clinical models of traumatic brain injury: systematic review and translational applications. J. Neurotrauma 40, 435–448 (2023).

    Article  PubMed  Google Scholar 

  172. Middleton, A., Fritz, S. L., Liuzzo, D. M., Newman-Norlund, R. & Herter, T. M. Using clinical and robotic assessment tools to examine the feasibility of pairing tDCS with upper extremity physical therapy in patients with stroke and TBI: a consideration-of-concept pilot study. NeuroRehabilitation 35, 741–754 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Ryan, J. L., Beal, D. S., Levac, D. E., Fehlings, D. L. & Wright, F. V. Integrating transcranial direct current stimulation into an existing inpatient physiotherapy program to enhance motor learning in an adolescent with traumatic brain injury: a case report. Phys. Occup. Ther. Pediatr. 43, 463–481 (2023).

    Article  PubMed  Google Scholar 

  174. Lutkenhoff, E. S. et al. The subcortical basis of outcome and cognitive impairment in TBI: a longitudinal cohort study. Neurology 95, E2398–E2408 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  175. Sandry, J. & Dobryakova, E. Global hippocampal and selective thalamic nuclei atrophy differentiate chronic TBI from non-TBI. Cortex 145, 37–56 (2021).

    Article  PubMed  Google Scholar 

  176. Sharp, D. J., Scott, G. & Leech, R. Network dysfunction after traumatic brain injury. Nat. Rev. Neurol. 10, 156–166 (2014).

    Article  PubMed  Google Scholar 

  177. Siegel, J. S., Shulman, G. L. & Corbetta, M. Mapping correlated neurological deficits after stroke to distributed brain networks. Brain Struct. Funct. 227, 3173–3187 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  178. Talozzi, L. et al. Latent disconnectome prediction of long-term cognitive-behavioural symptoms in stroke. Brain 146, 1963–1978 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Fox, M. D. Mapping symptoms to brain networks with the human connectome. N. Engl. J. Med. 379, 2237–2245 (2018).

    Article  CAS  PubMed  Google Scholar 

  180. Baldassarre, A., Metcalf, N. V., Shulman, G. L. & Corbetta, M. Brain networks’ functional connectivity separates aphasic deficits in stroke. Neurology 92, E125–E135 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  181. Siddiqi, S. H., Kording, K. P., Parvizi, J. & Fox, M. D. Causal mapping of human brain function. Nat. Rev. Neurosci. 23, 361–375 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  182. Lai, M. H. et al. Effectiveness and brain mechanism of multi-target transcranial alternating current stimulation (tACS) on motor learning in stroke patients: study protocol for a randomized controlled trial. Trials 25, 97 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Tashiro, S., Takemi, M., Yamada, S. & Tsuji, T. Synchronized application of closed-loop NMES and precision tACS in post-stroke hand rehabilitation: a protocol of neurorehabilitation trial. Ther. Adv. Chronic Dis. 15, 20406223241297396 (2024).

    Article  Google Scholar 

  184. Sinisalo, H. et al. Multi-locus transcranial magnetic stimulation with pulse-width modulation. Brain Stimul. 18, 948–956 (2025).

    Article  PubMed  Google Scholar 

  185. Siddiqi, S. H. & Fox, M. D. Targeting symptom-specific networks with transcranial magnetic stimulation. Biol. Psychiatry 95, 502–509 (2024).

    Article  PubMed  Google Scholar 

  186. Alekseichuk, I., Turi, Z., Amador de Lara, G., Antal, A. & Paulus, W. Spatial working memory in humans depends on theta and high gamma synchronization in the prefrontal cortex. Curr. Biol. 26, 1513–1521 (2016).

    Article  CAS  PubMed  Google Scholar 

  187. Diedrich, L., Kolhoff, H. I., Bergmann, C., Bähr, M. & Antal, A. Boosting working memory in the elderly: driving prefrontal theta–gamma coupling via repeated neuromodulation. Geroscience 47, 1425–1440 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  188. Reinhart, R. M. G. & Nguyen, J. A. Working memory revived in older adults by synchronizing rhythmic brain circuits. Nat. Neurosci. 22, 820–827 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Grover, S., Wen, W., Viswanathan, V., Gill, C. T. & Reinhart, R. M. G. Long-lasting, dissociable improvements in working memory and long-term memory in older adults with repetitive neuromodulation. Nat. Neurosci. 25, 1237–1246 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Xie, X., Hu, P., Tian, Y., Wang, K. & Bai, T. Transcranial alternating current stimulation enhances speech comprehension in chronic post-stroke aphasia patients: a single-blind sham-controlled study. Brain Stimul. 15, 1538–1540 (2022).

    Article  PubMed  Google Scholar 

  191. Antal, A. & Paulus, W. Transcranial alternating current stimulation (tACS). Front. Hum. Neurosci. 7, 317 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  192. Yang, S., Yi, Y. G. & Chang, M. C. The effect of transcranial alternating current stimulation on functional recovery in patients with stroke: a narrative review. Front. Neurol. 14, 1327383 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  193. Gamage, N. N. et al. Theta-gamma transcranial alternating current stimulation enhances ballistic motor performance in healthy young and older adults. Neurobiol. Aging 152, 1–12 (2025).

    Article  PubMed  Google Scholar 

  194. Grigutsch, L. S. et al. Differential effects of theta-gamma tACS on motor skill acquisition in young individuals and stroke survivors: a double-blind, randomized, sham-controlled study. Brain Stimul. 17, 1076–1085 (2024).

    Article  CAS  PubMed  Google Scholar 

  195. Zrenner, C. & Ziemann, U. Closed-loop brain stimulation. Biol. Psychiatry 95, 545–552 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  196. Zrenner, B. et al. Brain oscillation-synchronized stimulation of the left dorsolateral prefrontal cortex in depression using real-time EEG-triggered TMS. Brain Stimul. 13, 197–205 (2020).

    Article  PubMed  Google Scholar 

  197. Lieb, A. et al. Brain-oscillation-synchronized stimulation to enhance motor recovery in early subacute stroke: a randomized controlled double-blind three- arm parallel-group exploratory trial comparing personalized, non-personalized and sham repetitive transcranial magnetic stimulation (acronym: BOSS-STROKE). BMC Neurol. 23, 204 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  198. Mahmoud, W. et al. Brain state-dependent repetitive transcranial magnetic stimulation for motor stroke rehabilitation: a proof of concept randomized controlled trial. Front. Neurol. 15, 1427198 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  199. Kahana, M. J. et al. Biomarker-guided neuromodulation aids memory in traumatic brain injury. Brain Stimul. 16, 1086–1093 (2023).

    Article  PubMed  Google Scholar 

  200. Nojima, I. et al. Gait-combined closed-loop brain stimulation can improve walking dynamics in Parkinsonian gait disturbances: a randomised-control trial. J. Neurol. Neurosurg. Psychiatry 94, 938–944 (2023).

    Article  PubMed  Google Scholar 

  201. Grossman, N. et al. Noninvasive deep brain stimulation via temporally interfering electric fields. Cell 169, 1029–1041.e16 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  202. Huang, Z. et al. Low intensity focused ultrasound stimulation in stroke: a phase I safety and feasibility trial. Brain Stimul. 18, 179–187 (2025).

    Article  PubMed  Google Scholar 

  203. Yuksel, M. M. et al. Low-intensity focused ultrasound neuromodulation for stroke recovery: a novel deep brain stimulation approach for neurorehabilitation? IEEE Open J. Eng. Med. Biol. 4, 300–318 (2023).

    Article  PubMed  Google Scholar 

  204. Cataldi, S., Stanley, A. T., Miniaci, M. C. & Sulzer, D. Interpreting the role of the striatum during multiple phases of motor learning. FEBS J. 289, 2263–2281 (2022).

    Article  CAS  PubMed  Google Scholar 

  205. Berron, D., van Westen, D., Ossenkoppele, R., Strandberg, O. & Hansson, O. Medial temporal lobe connectivity and its associations with cognition in early Alzheimer’s disease. Brain 143, 1233–1248 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  206. Dues, D. J., Nguyen, A. P. T., Becker, K., Ma, J. & Moore, D. J. Hippocampal subfield vulnerability to α-synuclein pathology precedes neurodegeneration and cognitive dysfunction. npj Parkinsons Dis. 9, 125 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Ye, R. et al. Differential vulnerability of hippocampal subfields to amyloid and tau deposition in the Lewy body diseases. Neurology 102, e209460 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Krajcovicova, L., Klobusiakova, P. & Rektorova, I. Gray matter changes in Parkinson’s and Alzheimer’s disease and relation to cognition. Curr. Neurol. Neurosci. Rep. 19, 85 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  209. Železníková, Ž et al. Early changes in the locus coeruleus in mild cognitive impairment with Lewy bodies. Mov. Disord. 40, 276–284 (2025).

    Article  PubMed  Google Scholar 

  210. Lamoš, M. et al. Non-invasive temporal interference stimulation of the subthalamic nucleus in Parkinson’s disease reduces beta activity. Mov. Disord. 40, 1051–1060 (2025).

    Article  PubMed  PubMed Central  Google Scholar 

  211. Yang, C. et al. Transcranial temporal interference subthalamic stimulation for treating motor symptoms in Parkinson’s disease: a pilot study. Brain Stimul. 17, 1250–1252 (2024).

    Article  PubMed  Google Scholar 

  212. Wang, Y. et al. The safety and efficacy of applying a high-current temporal interference electrical stimulation in humans. Front. Hum. Neurosci. 18, 1484593 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  213. Antonenko, D. et al. Cognitive training and brain stimulation in patients with cognitive impairment: a randomized controlled trial. Alzheimers Res. Ther. 16, 6 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  214. O’Flaherty, D. & Ali, K. Recommendations for upper limb motor recovery: an overview of the UK and European rehabilitation after stroke guidelines (2023). Healthcare 12, 1433 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  215. Lee, S. H. & Yoo, Y. J. A literature review on optimal stimulation parameters of transcranial direct current stimulation for motor recovery after stroke. Brain Neurorehabil. 17, e24 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  216. Cole, E., O’Sullivan, S. J., Tik, M. & Williams, N. R. Accelerated theta burst stimulation: safety, efficacy, and future advancements. Biol. Psychiatry 95, 523–535 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  217. Sonmez, A. I. et al. Accelerated TMS for depression: a systematic review and meta-analysis. Psychiatry Res. 273, 770–781 (2019).

    Article  PubMed  Google Scholar 

  218. Pastore-Wapp, M., Nyffeler, T., Nef, T., Bohlhalter, S. & Vanbellingen, T. Non-invasive brain stimulation in limb praxis and apraxia: a scoping review in healthy subjects and patients with stroke. Cortex 138, 152–164 (2021).

    Article  PubMed  Google Scholar 

  219. Pastore-Wapp, M. et al. Feasibility of a combined intermittent theta-burst stimulation and video game-based dexterity training in Parkinson’s disease. J. Neuroeng. Rehabil. 20, 2 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  220. Lefaucheur, J. P. et al. Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS). Clin. Neurophysiol. 125, 2150–2206 (2014).

    Article  PubMed  Google Scholar 

  221. Fox, M. D., Halko, M. A., Eldaief, M. C. & Pascual-Leone, A. Measuring and manipulating brain connectivity with resting state functional connectivity magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS). Neuroimage 62, 2232–2243 (2012).

    Article  PubMed  Google Scholar 

  222. Siebner, H. R. et al. Transcranial magnetic stimulation of the brain: What is stimulated? – a consensus and critical position paper. Clin. Neurophysiol. 140, 59–97 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  223. Liu, A. et al. Immediate neurophysiological effects of transcranial electrical stimulation. Nat. Commun. 9, 5092 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  224. Reato, D., Rahman, A., Bikson, M. & Parra, L. C. Low-intensity electrical stimulation affects network dynamics by modulating population rate and spike timing. J. Neurosci. 30, 15067–15079 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  225. Moret, B., Donato, R., Nucci, M., Cona, G. & Campana, G. Transcranial random noise stimulation (tRNS): a wide range of frequencies is needed for increasing cortical excitability. Sci. Rep. 9, 15150 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

F.C.H., I.R. and M.P. were supported by a grant of the Swiss National Science Foundation (SNSF) project 320030L_197899 in cooperation with the Czech Science Foundation (GAČR) GF21-13462L (Novel individualized brain stimulation network-based approaches to improve cognition in healthy seniors and patients with mild cognitive impairment). I.R., M.P. and L.B. were supported from the Czech Ministry of Health project no. NW25-04-00142 (Non-invasive stimulation of deep brain structures for modulation of working memory) and project no. LX22NPO5107 (MEYS), financed by the European Union – Next Generation EU. F.C.H. was supported by the Defitech Foundation (NIN-PARK, Morges, Switzerland), the Bertarelli Foundation—Catalyst programme (Deep-MCI-T, Gstaad, Switzerland), the Wyss Center for Bio and Neuroengineering (the Lighthouse Partnership for AI-guided Neuromodulation, Geneva, Switzerland) and the AKIVA Foundation (nDBS-TBI, Crans-Montana, Switzerland).

Author information

Authors and Affiliations

  1. Applied Neuroscience Research Group, Central European Institute of Technology, Masaryk University, Brno, Czech Republic

    Irena Rektorová, Monika Pupíková & Luboš Brabenec

  2. First Department of Neurology, Faculty of Medicine and St. Anne’s University Hospital, Masaryk University, Brno, Czech Republic

    Irena Rektorová

  3. Defitech Chair of Clinical Neuroengineering, Neuro-X Institute (INX), Ecole Polytechnique Fédérale de Lausanne (EPFL), Geneva, Switzerland

    Lisa Fleury & Friedhelm C. Hummel

  4. Defitech Chair of Clinical Neuroengineering, INX, EPFL Valais, Clinique Romande de Réadaptation (CRR), Sion, Switzerland

    Lisa Fleury & Friedhelm C. Hummel

  5. Clinical Neuroscience, University of Geneva Medical School, Geneva, Switzerland

    Friedhelm C. Hummel

Authors
  1. Irena Rektorová
    View author publications

    Search author on:PubMed Google Scholar

  2. Monika Pupíková
    View author publications

    Search author on:PubMed Google Scholar

  3. Lisa Fleury
    View author publications

    Search author on:PubMed Google Scholar

  4. Luboš Brabenec
    View author publications

    Search author on:PubMed Google Scholar

  5. Friedhelm C. Hummel
    View author publications

    Search author on:PubMed Google Scholar

Contributions

All authors researched data for the article, wrote the article and reviewed and/or edited the manuscript before submission. I.R. and F.C.H. contributed substantially to discussion of the content.

Corresponding author

Correspondence to Irena Rektorová.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information

Nature Reviews Neurology thanks L. Bréchet, S. Jaberzadeh and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Glossary

Acetylcholinesterase inhibitors

A class of drugs that increase levels of the neurotransmitter acetylcholine by inhibiting its breakdown. These drugs are commonly used to treat cognitive symptoms in Alzheimer disease.

Closed-loop NIBS

A non-invasive brain stimulation approach in which stimulation is adapted in real time on the basis of ongoing brain activity, thereby increasing personalization and, potentially, effectiveness of neuromodulation.

Deep brain stimulation (DBS)

A neurosurgical procedure involving the implantation of electrodes into specific brain regions to modulate abnormal activity, commonly used to treat Parkinson disease.

Default-mode network (DMN)

A brain network that is active during rest and is involved in self-referential thinking and mind wandering.

Dementia Rating Scale-2

A clinical tool used to assess the severity of cognitive dysfunction and progression of dementia.

Diffusion tensor imaging

An MRI technique that maps white matter tracts by measuring the diffusion of water molecules in tissue.

Dorsal anterior cingulate cortex

A brain region involved in cognitive control, conflict monitoring and emotion regulation, forming part of the brain’s salience network.

Dorsolateral prefrontal cortex

A region of the frontal lobe that is involved in executive functions such as working memory, decision-making and cognitive control.

Frontotemporal dementia (FTD)

A group of disorders caused by progressive damage to the frontal and/or temporal lobes, often resulting in personality changes and language deficits.

Functional MRI (fMRI)

A technique for measuring and mapping brain activity on the basis of changes in blood flow.

Gamma-frequency stimulation

Stimulation in the range of ~40 Hz, linked to memory and attention and used in transcranial alternating current stimulation studies to enhance cognitive function.

Hypokinetic dysarthria

A speech disorder in people with Parkinson disease, characterized by reduced voice volume, monotone speech and articulation problems.

Long-term depression

A long-lasting decrease in synaptic strength, important for forgetting and learning flexibility.

Long-term potentiation

A cellular mechanism comprising persistent strengthening of synapses that is considered to underlie learning and memory.

Mild cognitive impairment (MCI)

A subtle but noticeable cognitive decline that is greater than expected for age but not severe enough to interfere substantially with daily life.

Mini-Mental State Examination

A brief clinical test that is used to assess cognitive function and screen for dementia.

Montreal Cognitive Assessment

A widely used cognitive screening test that is designed to detect mild cognitive impairment.

Phase–amplitude coupling

A neural mechanism whereby the amplitude of high-frequency brain waves is modulated by the phase of lower-frequency rhythms.

Primary motor cortex (M1)

A brain region that is responsible for voluntary muscle movements and represents a frequent target in motor rehabilitation and brain stimulation.

Resting motor threshold

The minimum intensity of transcranial magnetic stimulation that is needed to produce a motor-evoked potential in a target muscle while the muscle is at rest. It is used to individualize stimulation parameters and ensure safety and efficacy in transcranial magnetic stimulation protocols.

Stochastic resonance

A phenomenon whereby random noise enhances the brain’s ability to detect weak signals, possibly explaining the effects of transcranial random noise stimulation.

Supplementary motor area

A region in the medial frontal cortex that is involved in the planning and initiation of voluntary movements.

Theta-burst stimulation (TBS)

Theta-burst stimulation is a rapid form of repetitive transcranial magnetic stimulation that delivers bursts of stimulation at theta frequency to modulate cortical excitability. The bursts can be delivered intermittently (iTBS) or in a continuous train (cTBS).

Transcranial temporal interference stimulation (tTIS)

A relatively new technique that uses intersecting high-frequency currents to target deep brain regions non-invasively.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rektorová, I., Pupíková, M., Fleury, L. et al. Non-invasive brain stimulation: current and future applications in neurology. Nat Rev Neurol 21, 669–686 (2025). https://doi.org/10.1038/s41582-025-01137-z

Download citation

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41582-025-01137-z

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing