Advancing post-stroke cognitive rehabilitation through high-frequency neurostimulation: A retrospective evaluation of cortical excitability and biomarker modulation
Restricted accessResearch articleFirst published online September, 2025
Advancing post-stroke cognitive rehabilitation through high-frequency neurostimulation: A retrospective evaluation of cortical excitability and biomarker modulation
Post-stroke cognitive impairment (PSCI) poses significant challenges to patient independence, yet technological interventions like high-frequency repetitive transcranial magnetic stimulation (rTMS) remain underexplored in clinical neurorehabilitation.
Objective:
This study evaluates the integration of high-frequency rTMS into standard care, focusing on its technological efficacy in modulating neuroplasticity and serum biomarkers to enhance cognitive and functional recovery.
Methods:
A retrospective analysis of 80 PSCI patients (2021–2023) compared outcomes between a conventional care group (n = 30) and an rTMS group (n = 50) receiving 20 Hz stimulation (YRD-CCY-I device) targeting the dorsolateral prefrontal cortex. Key metrics included Montreal Cognitive Assessment (MoCA), Barthel Index (BI), cortical silent period (CL), central motor conduction time (CMCT), and serum neurotrophic factors (BDNF, VEGF, IGF-1).
Results:
Post-intervention, the rTMS group demonstrated superior MoCA scores (19.25 vs. 15.24, p = 0.001), BI (76.36 vs. 70.13, p = 0.001), and IADL (20.38 vs. 18.13, p = 0.001) compared to controls. Neurophysiological markers revealed prolonged CL (25.30 vs. 24.02 ms, p = 0.001) and shortened CMCT (12.05 vs. 12.98 ms, p = 0.001), alongside elevated BDNF (9.56 vs. 7.34 ng/mL), VEGF (156.48 vs. 110.54 pg/mL), and IGF-1 (153.74 vs. 112.90 ng/mL, p = 0.001). Overall efficacy was 94% for rTMS versus 73.33% for conventional care (p = 0.047).
Conclusion:
High-frequency rTMS, as a targeted neurostimulation technology, enhances cognitive recovery and cortical adaptability in PSCI by modulating neuroplasticity and upregulating neurotrophic biomarkers. These findings underscore its potential as a scalable adjunct in technology-driven neurorehabilitation programs.
ShinMSohnMKLeeJ, et al.Effect of cognitive reserve on risk of cognitive impairment and recovery after stroke: the KOSCO study. Stroke2020; 51: 99–107.
2.
HanJZYangYWangYF, et al.Effectiveness and safety of governor vessel acupuncture therapy for post-stroke cognitive impairment: a meta-analysis of randomized controlled trials. Ageing Res Rev2024; 99: 102355.
3.
MijajlovicMDPavlovicABraininM, et al.Post-stroke dementia - a comprehensive review. Bmc Med2017; 15: 11.
4.
SackATPanevaJKutheT, et al.Target engagement and brain state dependence of transcranial magnetic stimulation: implications for clinical practice. Biol Psychiat2024; 95: 536–544.
5.
ChenWLinHLyuM, et al.The potential role of leukoaraiosis in remodeling the brain network to buffer cognitive decline: a leukoaraiosis and disability study from Alzheimer's disease neuroimaging initiative. Quant Imag Med Surg2021; 11: 183–203.
6.
JokinenHGoncalvesNVigarioR, et al.Early-Stage white matter lesions detected by multispectral MRI segmentation predict progressive cognitive decline. Front Neurosci-Switz2015; 9: 455.
7.
SensenbrennerBRouaudOGraule-PetotA, et al.High prevalence of social cognition disorders and mild cognitive impairment long term after stroke. Alz Dis Assoc Dis2020; 34: 72–78.
8.
Mueller-SarnowskiFSollmannNSchroderA, et al.Neuronavigated repetitive transcranial magnetic stimulation as novel mapping technique provides insights into language function in primary progressive aphasia. Brain Imaging Behav2022; 16: 1208–1216.
9.
YanJZhangFNiuL, et al.High-frequency repetitive transcranial magnetic stimulation mitigates depression-like behaviors in CUMS-induced rats via FGF2/FGFR1/p-ERK signaling pathway. Brain Res Bull2022; 183: 94–103.
10.
WagnerEHonerWGSommerIE, et al.Repetitive transcranial magnetic stimulation (rTMS) for schizophrenia patients treated with clozapine. World J Biol Psychia2021; 22: 14–26.
11.
TangDLMcDanielAWatkinsKE. Disruption of speech motor adaptation with repetitive transcranial magnetic stimulation of the articulatory representation in primary motor cortex. Cortex2021; 145: 115–130.
12.
NguyenTDHieronymusFLorentzenR, et al.The efficacy of repetitive transcranial magnetic stimulation (rTMS) for bipolar depression: a systematic review and meta-analysis. J Affect Disorders2021; 279: 250–255.
13.
YuFHuangYChenT, et al.Repetitive transcranial magnetic stimulation promotes response inhibition in patients with major depression during the stop-signal task. J Psychiatr Res2022; 151: 427–438.
14.
ZinmanJKapoorASiK, et al.Men are at higher risk of screening positive for vascular cognitive impairment compared to women after stroke and transient ischemic attack. J Alzheimers Dis2023; 94: 89–94.
15.
QiuSYiWWangS, et al.The lasting effects of low-frequency repetitive transcranial magnetic stimulation on resting state EEG in healthy subjects. Ieee T Neur Sys Reh2020; 28: 832–841.
16.
WeiWYiXRuanJ, et al.The efficacy of repetitive transcranial magnetic stimulation on emotional processing in apathetic patients with Parkinson's disease: a placebo-controlled ERP study. J Affect Disorders2021; 282: 776–785.
17.
KhedrEMMohamedKOAliAM,et al.The effect of repetitive transcranial magnetic stimulation on cognitive impairment in Parkinson's disease with dementia: pilot study. Restor Neurol Neuros2020; 38: 55–66.
18.
YangGGuRKuboJ,et al.Is the efficacy of repetitive transcranial magnetic stimulation influenced by baseline severity of fatigue symptom in patients with myalgic encephalomyelitis. Int J Neurosci2020; 130: 64–70.
19.
TussisLSollmannNBoeckh-BehrensT, et al.The cortical distribution of first and second language in the right hemisphere of bilinguals - an exploratory study by repetitive navigated transcranial magnetic stimulation. Brain Imaging Behav2020; 14: 1034–1049.
20.
TrevizolAPDownarJVila-RodriguezF, et al.Effect of repetitive transcranial magnetic stimulation on anxiety symptoms in patients with major depression: an analysis from the THREE-D trial. Depress Anxiety2021; 38: 262–271.
21.
GatzinskyKBerghCLiljegrenA, et al.Repetitive transcranial magnetic stimulation of the primary motor cortex in management of chronic neuropathic pain: a systematic review. Scand J Pain2021; 21: 8–21.
22.
MengYZhangDHaiH, et al.Efficacy of coupling intermittent theta-burst stimulation and 1 Hz repetitive transcranial magnetic stimulation to enhance upper limb motor recovery in subacute stroke patients: a randomized controlled trial. Restor Neurol Neuros2020; 38: 109–118.
23.
GanHZhuJZhuoK, et al.High frequency repetitive transcranial magnetic stimulation of dorsomedial prefrontal cortex for negative symptoms in patients with schizophrenia: a double-blind, randomized controlled trial. Psychiat Res2021; 299: 113876.
24.
PerniaAMZorzoCPrietoMJ, et al.Equipment for repetitive transcranial magnetic stimulation. Ieee T Biomed Circ S2020; 14: 525–534.
25.
CantoneMLanzaGFisicaroF, et al.Evaluation and treatment of vascular cognitive impairment by transcranial magnetic stimulation. Neural Plast2020; 1: 1–17.
26.
CantoneMFisicaroFFerriR, et al.Sex differences in mild vascular cognitive impairment: a multimodal transcranial magnetic stimulation study. Plos One2023; 18: e0282751.
27.
LiSXiaoZ. Recent research progress on the use of transcranial magnetic stimulation in the treatment of vascular cognitive impairment. Neuropsych Dis Treat2024; 20: 1235–1246.
28.
LiXLinYLCunninghamDA, et al.Repetitive transcranial magnetic stimulation of the contralesional dorsal premotor Cortex for upper extremity motor improvement in severe stroke: study protocol for a pilot randomized clinical trial. Cerebrovasc Dis2022; 51: 557–564.
29.
BelsherBEBeechEHReddyMK, et al.Advances in repetitive transcranial magnetic stimulation for posttraumatic stress disorder: a systematic review. J Psychiatr Res2021; 138: 598–606.
30.
Arheix-ParrasSBarriosCPythonG, et al.A systematic review of repetitive transcranial magnetic stimulation in aphasia rehabilitation: leads for future studies. Neurosci Biobehav R2021; 127: 212–241.
31.
NicolettiVGFisicaroFAgugliaE, et al.Challenging the Pleiotropic Effects of Repetitive Transcranial Magnetic Stimulation in Geriatric Depression: A Multimodal Case Series Study. Biomedicines2023; 11.
32.
AlexopoulosGS. Mechanisms and treatment of late-life depression. Transl Psychiat2019; 9: 188.
33.
FitzsimmonsSOostraEPostmaTS, et al.Repetitive transcranial magnetic stimulation-induced neuroplasticity and the treatment of psychiatric disorders: state of the evidence and future opportunities. Biol Psychiat2024; 95: 592–600.
34.
SlanARCitrenbaumCCorlierJ, et al.The role of sex and age in the differential efficacy of 10 Hz and intermittent theta-burst (iTBS) repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD). J Affect Disorders2024; 366: 106–112.
35.
BadnjevićACifrekMKorugaD. Integrated software suite for diagnosis of respiratory diseases. Eurocon2013; 201: 564–568.
36.
HrvatFSpahićLPokvićLG,et al.Artificial neural networks for prediction of medical device performance based on conformity assessment data: infusion and perfusor pumps case study. 2020 9th Mediterranean Conference on Embedded Computing (MECO), Budva, Montenegro2020; 1–4.
37.
HafizovićLČauševićADeumićA,et al.The use of artificial intelligence in diagnostic medical imaging: systematic literature review,” 2021 IEEE 21st International Conference on Bioinformatics and Bioengineering (BIBE), Kragujevac, Serbia2021; 1–6.
38.
VeljovićEŠpirtović-HalilovićSMuratovićS, et al.Artificial Neural Network and Docking Study in Design and Synthesis of Xanthenes as Antimicrobial Agents. In: BadnjevicA (ed.) CMBEBIH 2017. 62. Sarajevo, B&H: Springer, 2017, pp.617–626.
39.
GeXZhangYXinT,et al.Effects of 10 Hz repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in the vegetative state. Exp Ther Med2021; 21: 206.
40.
LiangRWangLLiX, et al.Repetitive transcranial magnetic stimulation rescues simulated space complex environment-induced emotional and social impairments by enhancing neuronal excitability in the medial prefrontal cortex. Cereb Cortex2023; 33: 7148–7162.
41.
VidyaKLSrivastavaSSinghB,et al.Effect of priming on adjunctive repetitive transcranial magnetic stimulation in treatment of late life depression: protocol of a prospective randomized sham-controlled study. CNS Spectr.2022; 28(4): 514–520.
42.
ZhuHYinXYangH, et al.Repetitive transcranial magnetic stimulation enhances the neuronal excitability of mice by regulating dynamic characteristics of Granule cells’ Ion channels. Cogn Neurodynamics2023; 17: 431–443.
43.
SmrkeAAndersonPMGuliaA, et al.Future directions in the treatment of osteosarcoma. Cells-Basel2021; 10: 172.
44.
MendoncaTBritoRLunaP, et al.Repetitive transcranial magnetic stimulation on the modulation of cortical and spinal cord excitability in individuals with spinal cord injury. Restor Neurol Neuros2021; 39: 291–301.
