1. Introduction

Stroke is the second-leading cause of death and the third-leading cause of disability in the world, and patients with stroke often suffer from functional impairments and deficits [1]. Motor weakness, sensory dysfunction, speech disturbances, dysphagia, unilateral neglect, cognitive dysfunction, and emotional impairment in post-stroke patients will need long-term rehabilitation ^[2][3][4][2-4]. The pathology of stroke involves both the focal neurologic deficits and the impairment of the neural circuit or brain networks ^[5][6][5,6]. As a means of physical factor therapy, noninvasive brain stimulation (NIBS) is a physical therapy that can regulate specific regions in brain by electrical, magnetic, or ultrasound stimulation in vivo, thereby modulating the excitability of neurons and multiple brain functions[7] ^{[7][8][9][10]}[8-10].

The effects of NIBS on physical functions in post-stroke patients have been reported by extensive clinical research ^[11][12][11,12]. However, due to the small sample size (less than 30 individuals) and unstandardized stimulation parameters of clinical studies ^[13][14][15][13-15], NIBS has not yet been included in the standardized treatment protocols for post-stroke rehabilitation.

2. Overview of Neuromodulation and NIBS

Neuromodulation technology refers to the use of implantable or non-implantable techniques (e.g., electrical, magnetic, or ultrasonic methods) to obtain therapeutic effects by changing the function or state of the nervous system. Through this approach, neurons or nerve signal transduction in adjacent or distant parts of the stimulation site are excited, inhibited, or regulated, thereby changing nerve function and improving the quality of life of patients ^[10][11][12][10-12]. Noninvasive neuromodulation techniques mainly include transcranial magnetic stimulation (TMS), transcranial electrical stimulation (tES), transcranial focused ultrasound stimulation (tFUS), transcranial unfocused ultrasound stimulation (tUUS), and transcutaneous vagus nerve stimulation (tVNS), among which repetitive transcranial magnetic stimulation (rTMS) and tDCS have proven effective in treating depression and pain ^[16][17][18][16-18]. Due to the specific advantages of being noninvasive, painless, safe, and cheap, in addition to having different parameters and treatment modes, NIBS shows broad prospects for development.

3. Technology and Research Situation of NIBS

3.1 TMS

TMS induces electrical currents in the brain through electromagnetic induction caused by an energized coil placed on the scalp that is a highly effective, painless, and noninvasive brain stimulation procedure, causing changes in excitability and plasticity of the targeted cortical neuronal populations. Magnetic fields can penetrate the scalp and skull and generate subthreshold- or suprathreshold-induced currents in the cerebral cortex concurrently, which depolarize neurons to generate action potentials to modulate and stimulate neuronal activity in target areas, and then can mostly affect the cortex function by synchronizing activity in related brain regions [15]. The regulatory effect of TMS on the cerebral cortex is influenced by factors such as coil shape, stimulation site, frequency, intensity, dosage (number of pulses, time, and duration) and other parameters.

3.2 tES

tES refers to physical therapy using electrical current to stimulate the brain, and it has gained popularity as a long-term therapy for patients with neurological disorders due to its convenience and potential effects on the brain network [19]. tES is an NIBS technique in experimental and clinical fields, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), transcranial pulsed current stimulation (tPCS), and transcranial random noise stimulation (tRNS). Unlike tACS and tDCS, tPCS can intrigue randomly generated quadratic pulses, which may in turn increase endogenously generated brain oscillations, thereby facilitating the synchronization of deep brain structures with cortical activity [20]. Another promising alternative, tRNS, is a noisy electrical stimulation that increases cortical excitability through a random “noise” resonance [21]. Both of them are currently lacking in research, herein, the two most widely used tES techniques, tDCS and tACS, are summarized in the following section.

3.2.1 tDCS

tDCS mainly delivers low direct current to brain tissue through electrodes placed on the scalp. A constant electric field can impact the neurons in the cerebral cortex, thereby activating sodium-potassium pumps, calcium-dependent channels, and NMDA receptor activity to depolarize or hyperpolarize neuronal membrane potential ^[22][23][22,23], thus regulating neuronal activity and cortical excitability. However, unlike TMS, tDCS does not induce action potentials directly, whereby stimulation sites are more scattered. Its effects are thought to be achieved by altering the polarity of the membrane to change their probability of triggering action potentials, thus modulating the activation of neurons in the stimulated area. The parameters of tDCS have a decisive effect on its biological effects [24], including electrode shape, size, number, placement, polarity, stimulation intensity, duration, and stimulation waveform ^[24][25][26][24-26], in which slight changes will produce distinctly different effects [27].

3.2.2 tACS

tACS selectively enhances synaptic connectivity in neuronal circuits and synaptic plasticity by modulating the brain’s intrinsic endogenous neural oscillatory patterns and altering neurotransmitter levels [28]. Then, tACS ultimately improves the coordinated activity between local brain areas and brain regions ^[19][29][19,29]. Unlike TMS and tDCS, tACS completely avoids skin irritations [19]. It stimulates cortical neurons with sinusoidal or biphasic alternating current, modulates endogenous brain oscillations, and induces changes in synaptic plasticity to improve long-term brain function and depressive symptoms ^[30][31][32][30-32]. tACS uses different parameter stimulation electrodes, alternating current to stimulate specific targets. There are no acknowledged parameters, including stimulation frequency, intensity, phase, and duration, which may influence the effects of tACS.

3.3 tFUS

Ultrasound is an acoustic wave with a frequency greater than the hearing detection level of the human ear (>20 kHz); it is a mechanical wave generated by the vibration of a sound source and propagated through a compressed and expanded medium. tFUS, especially MR-guided focused ultrasound (MRgFUS) [8], combines the properties of deep focus targeting with high spatial resolution. It can stimulate deep and relatively superficial brain tissue in a precise, stable, focused, and noninvasive manner [33], and it has become one of the hot spots in basic and clinical research. The neuromodulatory effect of tFUS is mainly produced by the mechanical, thermal, and cavitation effects of ultrasound. By changing the frequency, intensity, pulse repetition frequency, pulse width, and duration of the ultrasound, the neurons at the stimulation site are activated or inhibited, thus regulating the neural function [9].

3.4 tVNS

tVNS involves applying electrical stimulation to peripheral vagus nerves. It transmits signals to the brain, causing changes in brain electrical activity and neurotransmitters, thereby modulating the functional activity of neurons [34]. tVNS can be mainly classified into two types: one is transcutaneous auricular vagus nerve stimulation (taVNS), which consists of electrically stimulating the auricular branch of the vagus nerve ^[35] [35] (especially the auricular vessels); and the other is transcutaneous cervical vagus nerve stimulation (tcVNS), which consists of electrically stimulating the vagus nerve in the carotid sheath of the anterolateral neck [36]. tVNS exerts neuromodulatory effects, mainly by transmitting electrical stimulation to the brain, as well as increasing the plasticity of neural activity in the left prefrontal cortex, motor cortex, sensory cortex [37], right caudate nucleus, middle cingulate gyrus, and cerebellum [38]. It also enhances the plasticity of corticospinal motor pathways by activating widely projected neuromodulatory systems [39], ultimately increasing synaptic connections to muscle tissue and enhancing motor function [40].

4. Application of NIBS in Post-Stroke Rehabilitation

The use of NIBS in clinical practice is continuously developing, and its role and position in neurological rehabilitation have become increasingly prominent. Combined with adjunctive exercises, the application of NIBS has been extrapolated from the treatment of post-stroke motor dysfunction to sensory disorders, aphasia, dysphagia, unilateral neglect, cognitive dysfunction, depression, and even disorders of consciousness in the acute phase [41].

5. Current Status and Prospects

5.1 Effectiveness and Sustainability

Due to the heterogeneity of stroke injury location and the differences in the site, frequency, and duration of NIBS stimulation, it is difficult to use uniform criteria to judge the effectiveness and long-term efficacy of NIBS. However, there is a time-dependent effect of NIBS. In particular, cognitive function is significantly correlated with the number and duration of stimulation [42], which has been well-validated by recent studies. The session of commonly used treatments for NIBS reported in studies generally ranges from 5 to 20 (1–4 weeks), with follow-up usually after the end of treatment; the longest reported effective duration is 1 year [43].

5.2 Limitations and Future Trends

5.2.1. Small Samples, and Insufficient and Short Follow-Up Studies

Firstly, most studies on the application of NIBS in stroke only included small sample sizes, usually fewer than 30 individuals in each group ^[44][45][46][44-46]. Secondly, most of the current studies focused on motor function, speech, and cognitive function after stroke, mainly using rTMS and tDCS for intervention, while there are fewer studies investigating other functional impairments or using alternate NIBS techniques. Lastly, the follow-up duration after NIBS intervention in stroke patients was relatively short. Most studies assessed outcome indicators at the end of the intervention course, with the longest follow-up duration being 1 year [47].

5.2.2. Variety of Therapeutic Options and Prospects

In previous studies, M1 and DLPFC were most frequently used as single stimulation targets, while other brain regions such as supplementary motor areas, S1, dACC, thalamus, and hippocampus have been rarely reported. Some recent studies found that functional connections are damaged in post-stroke patients [48]. Stimulating one or two targets of the same neural circuit can modulate the whole circuit and achieve better functional recovery. PAS protocols ^[49] [49] including within-system, cross-system, and cortico–cortical, which are composed of rTMS or peripheral stimulation, provide the concept and feasibility of bi-targeted neuromodulation, especially cortico–cortical PAS ^[50][51][50,51]. On the basis of the understanding of brain network doctrine and the summary analysis of existing studies, we believe that neuromodulation can go from single-target stimulation to two-target stimulation, and then to multi-target stimulation of the same circuit, eventually achieving stimulation of the whole brain network, which will be a future development direction. Animal experiments have reported similar approaches, such as modulation of touch being able to improve dexterous motor function ^[52][52].

Secondly, the protocols of these neuromodulation techniques in NIBS applied in stroke patients still need further optimization and can be combined into exponentially increasing stimulation programs depending on the choice of stimulation location, intensity, frequency, total time, and whether the stimulation is continuous or not ^[53][53], among which the treatment parameters that may lead to adverse effects need further modification ^[54][54]. The optimal parameters for TMS, tES, tFUS, and tVNS need to be more clearly defined and harmonized, and more comprehensive well-designed high-quality studies on the selection of optimal parameters are expected to provide evidence for the early development of standardized therapeutic protocols for various techniques of NIBS.

Lastly, most of the available studies focused on examining the therapeutic effects and neuromodulatory mechanisms of a particular technique in stroke, but the possibility of combining different NIBS techniques in stroke is often ignored. The main reasons for this may be the difficulty in assessing the effects of combining various techniques and the difficulty in explaining the interactions between the combinations. Given the differences in the mechanisms of various NIBS, the integration of different techniques may enhance the neuromodulatory effect, and different NIBS combination models have been reported in the literature for application in stroke patients, such as rTMS-tDCS and TMS-tACS [55]. There are also many studies combining NIBS with fMRI or EEG [51] techniques, for example, TMS-EEG, and TMS-fMRI can be used in combination to better individualize and synchronize neuromodulation in stroke patients, revealing possible remote top-down effect at the neural population level [56]. Furthermore, the combination of cathodal cerebellar tDCS and visual feedback was reported to improve balance control in a healthy population [57] and these findings should also be considered to deeply elaborate the mechanism of NIBS techniques in post-stroke dysfunction, which will be a future direction of development.

6. Conclusions

NIBS can be used as a therapeutic measure in post-stroke neurorehabilitation to promote recovery of functional impairment in patients when combined with movement training or other rehabilitation treatments. Overcoming the current limitations, NIBS can provide better and more precise modulation of neural circuits and neural networks, reduce adverse effects, and improve therapeutic effectiveness.

References

[1] Bolognini, N.;Russo, C.;Souza Carneiro, M.I.;Nicotra, A.;Olgiati, E.;Spandri, V.;Agostoni, E.;Salmaggi, A.;Vallar, G.Bi‐hemispheric transcranial direct current stimulation for upper‐limb hemiparesis in acute stroke: a randomized, double‐blind, sham‐controlled trial.EUROPEAN JOURNAL OF NEUROLOGY 2020,27,2473-2482. 10.1111/ene.14451.

[2] Geed, S.;Feit, P.;Edwards, D.F.;Dromerick, A.W.Why Are Stroke Rehabilitation Trial Recruitment Rates in Single Digits?Frontiers in Neurology 2021,12,674237. 10.3389/fneur.2021.674237.

[3] Kim, C.;Chu, H.;Kang, G.;Sung, K.;Kang, D.G.;Lee, H.S.;Lee, S.Difference in gait recovery rate of hemiparetic stroke patients according to paralyzed side.MEDICINE 2019,98,e18023. 10.1097/MD.0000000000018023.

[4] Labberton, A.S.;Barra, M.;Ronning, O.M.;Thommessen, B.;Churilov, L.;Cadilhac, D.A.;Lynch, E.A.Patient and service factors associated with referral and admission to inpatient rehabilitation after the acute phase of stroke in Australia and Norway.BMC HEALTH SERVICES RESEARCH 2019,19,871. 10.1186/s12913-019-4713-x.

[5] Sun, H.;He, X.;Tao, X.;Hou, T.;Chen, M.;He, M.;Liao, H.The CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity after stroke.Journal of Neuroinflammation 2020,17,171. 10.1186/s12974-020-01845-x.

[6] Wiest, R.;Abela, E.;Missimer, J.;Schroth, G.;Hess, C.W.;Sturzenegger, M.;Wang, D.J.;Weder, B.;Federspiel, A.Interhemispheric cerebral blood flow balance during recovery of motor hand function after ischemic stroke--a longitudinal MRI study using arterial spin labeling perfusion.PLoS One 2014,9,e106327. 10.1371/journal.pone.0106327.

[7] Brunelin, J.;Adam, O.;Mondino, M.Recent advances in noninvasive brain stimulation for schizophrenia.CURRENT OPINION IN PSYCHIATRY 2022,35,338-344. 10.1097/YCO.0000000000000809.

[8] Hynynen, K.;Jones, R.M.Image-guided ultrasound phased arrays are a disruptive technology for non-invasive therapy.PHYSICS IN MEDICINE AND BIOLOGY 2016,61,R206-R248. 10.1088/0031-9155/61/17/R206.

[9] Kim, H.;Chiu, A.;Lee, S.D.;Fischer, K.;Yoo, S.Focused Ultrasound-mediated Non-invasive Brain Stimulation: Examination of Sonication Parameters.Brain Stimulation 2014,7,748-756. 10.1016/j.brs.2014.06.011.

[10] Strube, W.;Bunse, T.;Malchow, B.;Hasan, A.Efficacy and interindividual variability in motor-cortex plasticity following anodal tDCS and paired-associative stimulation.NEURAL PLASTICITY 2015,2015,530423. 10.1155/2015/530423.

[11] Baig, S.S.;Falidas, K.;Laud, P.J.;Snowdon, N.;Farooq, M.U.;Ali, A.;Majid, A.;Redgrave, J.N.Transcutaneous Auricular Vagus Nerve Stimulation with Upper Limb Repetitive Task Practice May Improve Sensory Recovery in Chronic Stroke.Journal of Stroke and Cerebrovascular Diseases 2019,28,104348. 10.1016/j.jstrokecerebrovasdis.2019.104348.

[12] Cha, H.G.;Kim, M.K.Effects of repetitive transcranial magnetic stimulation on arm function and decreasing unilateral spatial neglect in subacute stroke: a randomized controlled trial.CLINICAL REHABILITATION 2016,30,649-656. 10.1177/0269215515598817.

[13] Di Pino, G.;Pellegrino, G.;Assenza, G.;Capone, F.;Ferreri, F.;Formica, D.;Ranieri, F.;Tombini, M.;Ziemann, U.;Rothwell, J.C.et al.Modulation of brain plasticity in stroke: a novel model for neurorehabilitation.Nature Reviews Neurology 2014,10,597-608. 10.1038/nrneurol.2014.162.

[14] Lefaucheur, J.P.;Antal, A.;Ayache, S.S.;Benninger, D.H.;Brunelin, J.;Cogiamanian, F.;Cotelli, M.;De Ridder, D.;Ferrucci, R.;Langguth, B.et al.Evidence-based guidelines on the therapeutic use of transcranial direct current stimulation (tDCS).CLINICAL NEUROPHYSIOLOGY 2017,128,56-92. 10.1016/j.clinph.2016.10.087.

[15] Lefaucheur, J.;Aleman, A.;Baeken, C.;Benninger, D.H.;Brunelin, J.;Di Lazzaro, V.;Filipović, S.R.;Grefkes, C.;Hasan, A.;Hummel, F.C.et al.Evidence-based guidelines on the therapeutic use of repetitive transcranial magnetic stimulation (rTMS): An update (2014–2018).CLINICAL NEUROPHYSIOLOGY 2020,131,474-528. 10.1016/j.clinph.2019.11.002.

[16] Gatzinsky, K.;Bergh, C.;Liljegren, A.;Silander, H.;Samuelsson, J.;Svanberg, T.;Samuelsson, O.Repetitive transcranial magnetic stimulation of the primary motor cortex in management of chronic neuropathic pain: a systematic review.Scandinavian Journal of Pain 2021,21,8-21. 10.1515/sjpain-2020-0054.

[17] Jing, Y.;Zhao, N.;Deng, X.P.;Feng, Z.J.;Huang, G.F.;Meng, M.;Zang, Y.F.;Wang, J.Pregenual or subgenual anterior cingulate cortex as potential effective region for brain stimulation of depression.Brain and Behavior 2020,10,e1591. 10.1002/brb3.1591.

[18] Timäus, C.;Vogelgsang, J.;Kis, B.;Radenbach, K.;Wolff-Menzler, C.;Mavridou, K.;Gyßer, S.;Hessmann, P.;Wiltfang, J.Current clinical practice of electroconvulsive therapy and repetitive transcranial magnetic stimulation in psychiatry, a German sample.EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE 2021,271,181-190. 10.1007/s00406-020-01099-x.

[19] Liu, A.;Voroslakos, M.;Kronberg, G.;Henin, S.;Krause, M.R.;Huang, Y.;Opitz, A.;Mehta, A.;Pack, C.C.;Krekelberg, B.et al.Immediate neurophysiological effects of transcranial electrical stimulation.Nature Communications 2018,9,5092. 10.1038/s41467-018-07233-7.

[20] Thibaut, A.;Russo, C.;Morales-Quezada, L.;Hurtado-Puerto, A.;Deitos, A.;Freedman, S.;Carvalho, S.;Fregni, F.Neural signature of tDCS, tPCS and their combination: Comparing the effects on neural plasticity.NEUROSCIENCE LETTERS 2017,637,207-214. 10.1016/j.neulet.2016.10.026.

[21] Pena, J.;Sampedro, A.;Ibarretxe-Bilbao, N.;Zubiaurre-Elorza, L.;Ojeda, N.Improvement in creativity after transcranial random noise stimulation (tRNS) over the left dorsolateral prefrontal cortex.Scientific Reports 2019,9,7116. 10.1038/s41598-019-43626-4.

[22] Ebonsi, P.;Cuomo, D.;Martella, G.;Madeo, G.;Schirinzi, T.;Puglisi, F.;Ponterio, G.;Pisani, A.Centrality of striatal cholinergic transmission in Basal Ganglia function.Frontiers in Neuroanatomy 2011,5,6. 10.3389/fnana.2011.00006.

[23] Goff, D.C.D-cycloserine in Schizophrenia: New Strategies for Improving Clinical Outcomes by Enhancing Plasticity.Current Neuropharmacology 2017,15,21-34. 10.2174/1570159x14666160225154812.

[24] Li, L.M.;Uehara, K.;Hanakawa, T.The contribution of interindividual factors to variability of response in transcranial direct current stimulation studies.Frontiers in Cellular Neuroscience 2015,9,181. 10.3389/fncel.2015.00181.

[25] Groppa, S.;Oliviero, A.;Eisen, A.;Quartarone, A.;Cohen, L.G.;Mall, V.;Kaelin-Lang, A.;Mima, T.;Rossi, S.;Thickbroom, G.W.et al.A practical guide to diagnostic transcranial magnetic stimulation: report of an IFCN committee.CLINICAL NEUROPHYSIOLOGY 2012,123,858-882. 10.1016/j.clinph.2012.01.010.

[26] Hsu, G.;Farahani, F.;Parra, L.C.Cutaneous sensation of electrical stimulation waveforms.Brain Stimulation 2021,14,693-702. 10.1016/j.brs.2021.04.008.

[27] Woods, A.J.;Antal, A.;Bikson, M.;Boggio, P.S.;Brunoni, A.R.;Celnik, P.;Cohen, L.G.;Fregni, F.;Herrmann, C.S.;Kappenman, E.S.et al.A technical guide to tDCS, and related non-invasive brain stimulation tools.CLINICAL NEUROPHYSIOLOGY 2016,127,1031-1048. 10.1016/j.clinph.2015.11.012.

[28] Zaehle, T.;Rach, S.;Herrmann, C.S.Transcranial alternating current stimulation enhances individual alpha activity in human EEG.PLoS One 2010,5,e13766. 10.1371/journal.pone.0013766.

[29] Kar, K.;Ito, T.;Cole, M.W.;Krekelberg, B.Transcranial alternating current stimulation attenuates BOLD adaptation and increases functional connectivity.JOURNAL OF NEUROPHYSIOLOGY 2020,123,428-438. 10.1152/jn.00376.2019.

[30] Elyamany, O.;Leicht, G.;Herrmann, C.S.;Mulert, C.Transcranial alternating current stimulation (tACS): from basic mechanisms towards first applications in psychiatry.EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE 2021,271,135-156. 10.1007/s00406-020-01209-9.

[31] Tavakoli, A.V.;Yun, K.Transcranial Alternating Current Stimulation (tACS) Mechanisms and Protocols.Frontiers in Cellular Neuroscience 2017,11,214. 10.3389/fncel.2017.00214.

[32] Vosskuhl, J.;Struber, D.;Herrmann, C.S.[Transcranial alternating current stimulation. Entrainment and function control of neuronal networks].NERVENARZT 2015,86,1516-1522. 10.1007/s00115-015-4317-6.

[33] Kubanek, J.Neuromodulation with transcranial focused ultrasound.Neurosurgical Focus 2018,44,E14. 10.3171/2017.11.FOCUS17621.

[34] Borges, U.;Knops, L.;Laborde, S.;Klatt, S.;Raab, M.Transcutaneous Vagus Nerve Stimulation May Enhance Only Specific Aspects of the Core Executive Functions. A Randomized Crossover Trial.Frontiers in Neuroscience 2020,14,523. 10.3389/fnins.2020.00523.

[35] Vosseler, A.;Zhao, D.;Fritsche, L.;Lehmann, R.;Kantartzis, K.;Small, D.M.;Peter, A.;Häring, H.;Birkenfeld, A.L.;Fritsche, A.et al.No modulation of postprandial metabolism by transcutaneous auricular vagus nerve stimulation: a cross-over study in 15 healthy men.Scientific Reports 2020,10,20466. 10.1038/s41598-020-77430-2.

[36] Wittbrodt, M.T.;Gurel, N.Z.;Nye, J.A.;Ladd, S.;Shandhi, M.M.H.;Huang, M.;Shah, A.J.;Pearce, B.D.;Alam, Z.S.;Rapaport, M.H.et al.Non-invasive vagal nerve stimulation decreases brain activity during trauma scripts.Brain Stimulation 2020,13,1333-1348. 10.1016/j.brs.2020.07.002.

[37] Takahashi, H.;Shiramatsu, T.I.;Hitsuyu, R.;Ibayashi, K.;Kawai, K.Vagus nerve stimulation (VNS)-induced layer-specific modulation of evoked responses in the sensory cortex of rats.Scientific Reports 2020,10,8932. 10.1038/s41598-020-65745-z.

[38] Badran, B.W.;Dowdle, L.T.;Mithoefer, O.J.;LaBate, N.T.;Coatsworth, J.;Brown, J.C.;DeVries, W.H.;Austelle, C.W.;McTeague, L.M.;George, M.S.Neurophysiologic effects of transcutaneous auricular vagus nerve stimulation (taVNS) via electrical stimulation of the tragus: A concurrent taVNS/fMRI study and review.Brain Stimulation 2018,11,492-500. 10.1016/j.brs.2017.12.009.

[39] Collins, L.;Boddington, L.;Steffan, P.J.;McCormick, D.Vagus nerve stimulation induces widespread cortical and behavioral activation.CURRENT BIOLOGY 2021,31,2088-2098. 10.1016/j.cub.2021.02.049.

[40] Morrison, R.A.;Hulsey, D.R.;Adcock, K.S.;Rennaker, R.L.;Kilgard, M.P.;Hays, S.A.Vagus nerve stimulation intensity influences motor cortex plasticity.Brain Stimulation 2019,12,256-262. 10.1016/j.brs.2018.10.017.

[41] Krewer, C.;Thibaut, A.Non-invasive brain stimulation for treatment of severe disorders of consciousness in people with acquired brain injury.Cochrane Database of Systematic Reviews 2020,2020,D13533. 10.1002/14651858.CD013533.

[42] van Lieshout, E.;van Hooijdonk, R.F.;Dijkhuizen, R.M.;Visser-Meily, J.;Nijboer, T.The Effect of Noninvasive Brain Stimulation on Poststroke Cognitive Function: A Systematic Review.NEUROREHABILITATION AND NEURAL REPAIR 2019,33,355-374. 10.1177/1545968319834900.

[43] Dawson, J.;Pierce, D.;Dixit, A.;Kimberley, T.J.;Robertson, M.;Tarver, B.;Hilmi, O.;McLean, J.;Forbes, K.;Kilgard, M.P.et al.Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke.STROKE 2016,47,143-150. 10.1161/STROKEAHA.115.010477.

[44] Baig, S.S.;Kamarova, M.;Ali, A.;Su, L.;Dawson, J.;Redgrave, J.N.;Majid, A.Transcutaneous vagus nerve stimulation (tVNS) in stroke: the evidence, challenges and future directions.Autonomic Neuroscience 2022,237,102909. 10.1016/j.autneu.2021.102909.

[45] Elsner, B.;Kwakkel, G.;Kugler, J.;Mehrholz, J.Transcranial direct current stimulation (tDCS) for improving capacity in activities and arm function after stroke: a network meta-analysis of randomised controlled trials.Journal of NeuroEngineering and Rehabilitation 2017,14,95. 10.1186/s12984-017-0301-7.

[46] van Lieshout, E.C.C.;van der Worp, H.B.;Visser-Meily, J.M.A.;Dijkhuizen, R.M.Timing of Repetitive Transcranial Magnetic Stimulation Onset for Upper Limb Function After Stroke: A Systematic Review and Meta-Analysis.Frontiers in Neurology 2019,10,1269. 10.3389/fneur.2019.01269.

[47] Dawson, J.;Pierce, D.;Dixit, A.;Kimberley, T.J.;Robertson, M.;Tarver, B.;Hilmi, O.;McLean, J.;Forbes, K.;Kilgard, M.P.et al.Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke.STROKE 2016,47,143-150. 10.1161/STROKEAHA.115.010477.

[48] Ryu, S.;Lee, S.H.;Kim, S.U.;Yoon, B.W.Human neural stem cells promote proliferation of endogenous neural stem cells and enhance angiogenesis in ischemic rat brain.Neural Regeneration Research 2016,11,298-304. 10.4103/1673-5374.177739.

[49] Palmer, J.A.;Wolf, S.L.;Borich, M.R.Paired associative stimulation modulates corticomotor excitability in chronic stroke: A preliminary investigation.RESTORATIVE NEUROLOGY AND NEUROSCIENCE 2018,36,183-194. 10.3233/RNN-170785.

[50] Guidali, G.;Roncoroni, C.;Bolognini, N.Paired associative stimulations: Novel tools for interacting with sensory and motor cortical plasticity.BEHAVIOURAL BRAIN RESEARCH 2021,414,113484. 10.1016/j.bbr.2021.113484.

[51] Kuo, I.;Tang, C.;Tsai, Y.;Tang, S.;Lin, C.;Hsu, S.;Liang, W.;Juan, C.;Zich, C.;Stagg, C.J.et al.Neurophysiological signatures of hand motor response to dual-transcranial direct current stimulation in subacute stroke: a TMS and MEG study.Journal of NeuroEngineering and Rehabilitation 2020,17,72. 10.1186/s12984-020-00706-1.

[52] Conner, J.M.;Bohannon, A.;Igarashi, M.;Taniguchi, J.;Baltar, N.;Azim, E.Modulation of tactile feedback for the execution of dexterous movement.SCIENCE 2021,374,316-323. 10.1126/science.abh1123.

[53] Downar, J.;Daskalakis, Z.J.New Targets for rTMS in Depression: A Review of Convergent Evidence.Brain Stimulation 2013,6,231-240. 10.1016/j.brs.2012.08.006.

[54] Gupta, A.;Adnan, M.Hypomania Risk in Noninvasive Brain Stimulation.Cureus Journal of Medical Science 2018,10,e2204. 10.7759/cureus.2204.

[55] Raco, V.;Bauer, R.;Tharsan, S.;Gharabaghi, A.Combining TMS and tACS for Closed-Loop Phase-Dependent Modulation of Corticospinal Excitability: A Feasibility Study.Frontiers in Cellular Neuroscience 2016,10,143. 10.3389/fncel.2016.00143.

[56] Bestmann, S.;Ruff, C.C.;Blankenburg, F.;Weiskopf, N.;Driver, J.;Rothwell, J.C.Mapping causal interregional influences with concurrent TMS–fMRI.EXPERIMENTAL BRAIN RESEARCH 2008,191,383-402. 10.1007/s00221-008-1601-8.

[57] Emadi, A.M.;Villa-Sanchez, B.;Raneri, F.;Dametto, S.;Tinazzi, M.;Fiorio, M.Cathodal Cerebellar tDCS Combined with Visual Feedback Improves Balance Control.CEREBELLUM 2020,19,812-823. 10.1007/s12311-020-01172-0.