无创迷走神经刺激在帕金森病中的研究进展
Research and Progress of Noninvasive Vagus Nerve Stimulation in Parkinson’s Disease
DOI: 10.12677/ACM.2024.141249, PDF,    科研立项经费支持
作者: 廖金成*, 李 鑫, 王 怡, 康富丽, 蔡青青:重庆医科大学,重庆;中国科学院重庆绿色智能技术研究院,重庆;中国科学院大学重庆学院,重庆;重庆市人民医院神经内科,重庆;张晖集:重庆医科大学,重庆;薛锐灵:重庆医科大学,重庆;中国科学院重庆绿色智能技术研究院,重庆;中国科学院大学重庆学院,重庆;重庆市人民医院康复医学科,重庆;马璟曦#:重庆医科大学,重庆;重庆市人民医院神经内科,重庆
关键词: 帕金森病迷走神经刺激冻结步态Parkinson’s Disease Vagus Nerve Stimulation Freezing of Gait
摘要: 帕金森病(Parkinson’s disease, PD)是一种常见的神经系统疾病,其具有多种运动性和非运动性症状特征。药物治疗是现在治疗PD的主要方法,但常常也带来一些严重的副作用。因此,探究新的治疗方法,为治疗PD添砖加瓦是必要的。迷走神经刺激是一种新兴的神经调控技术,具有抗炎、神经保护的作用,这为PD的治疗提供了新思路。本综述总结了目前国内外迷走神经刺激在PD中的研究,其中重点放在了PD步态障碍的研究上。迷走神经具有改善冻结步态的作用,此外对PD病人的认知功能、吞咽功能、焦虑抑郁、胃肠道功能有潜在的治疗作用。
Abstract: Parkinson’s disease is a common neurological disorder with a variety of motor and non-motor symptoms. Drug therapy is the main treatment for Parkinson’s disease, but it often comes with some serious side effects. Therefore, it is necessary to explore new therapeutic methods for the treatment of Parkinson’s disease. Vagus nerve stimulation is a new neuroregulatory technique with anti-inflammatory and neuroprotective effects, which provides a new idea for the treatment of Par-kinson’s disease. This review summarizes the current research on vagus nerve stimulation in Par-kinson’s disease at home and abroad, and focuses on gait disorders in Parkinson’s disease. Vagus nerve can improve frozen gait, and has potential therapeutic effect on cognitive function, swallowing function, anxiety and depression, gastrointestinal function in patients with Parkinson’s disease.
文章引用:廖金成, 李鑫, 张晖集, 薛锐灵, 王怡, 康富丽, 蔡青青, 马璟曦. 无创迷走神经刺激在帕金森病中的研究进展[J]. 临床医学进展, 2024, 14(1): 1741-1751. https://doi.org/10.12677/ACM.2024.141249

参考文献

[1] Bloem, B.R., Okun, M.S. and Klein, C. (2021) Parkinson’s Disease. The Lancet, 397, 2284-2303. [Google Scholar] [CrossRef
[2] Abdelnaby, R., Elsayed, M., Mohamed, K.A., et al. (2021) Vagus Nerve Ultrasonography in Parkinson’s Disease: A Systematic Review and Meta-Analysis. Autonomic Neurosci-ence, 234, Article 102835. [Google Scholar] [CrossRef] [PubMed]
[3] Almikhlafi, M.A. (2023) The Role of Exercise in Parkinson’s Disease. Neurosciences (Riyadh), 28, 4-12. [Google Scholar] [CrossRef] [PubMed]
[4] Liu, J., Liu, W., Lu, Y., et al. (2018) Piperlongumine Restores the Balance of Autophagy and Apoptosis by Increasing BCL2 Phosphorylation in Rotenone-Induced Parkinson Disease Models. Autophagy, 14, 845-861. [Google Scholar] [CrossRef] [PubMed]
[5] Krishnan, U.M. (2021) Biomaterials in the Treatment of Par-kinson’s Disease. Neurochemistry International, 145, Article 105003. [Google Scholar] [CrossRef] [PubMed]
[6] Church, F.C. (2021) Treatment Options for Motor and Non-Motor Symptoms of Parkinson’s Disease. Biomolecules, 11, Article 612. [Google Scholar] [CrossRef] [PubMed]
[7] Mantri, S., Morley, J.F. and Siderowf, A.D. (2019) The Importance of Preclinical Diagnostics in Parkinson Disease. Parkinsonism & Related Disorders, 64, 20-28. [Google Scholar] [CrossRef] [PubMed]
[8] Liu, C.F., Wang, T., Zhan, S.Q., et al. (2018) Management Recommendations on Sleep Disturbance of Patients with Parkinson’s Disease. Chinese Medical Journal (Engl), 131, 2976-2985. [Google Scholar] [CrossRef] [PubMed]
[9] Scott, S. (2002) Understanding the Challenge of Par-kinson’s Disease. Nursing Standard, 16, 48-53; Quiz 54-45. [Google Scholar] [CrossRef] [PubMed]
[10] Armstrong, M.J. and Okun, M.S. (2020) Diagnosis and Treatment of Parkinson Disease: A Review. JAMA, 323, 548-560. [Google Scholar] [CrossRef] [PubMed]
[11] Farrand, A.Q., Helke, K.L., Gregory, R.A., Gooz, M., Hinson, V.K. and Boger, H.A. (2017) Vagus Nerve Stimulation Improves Locomotion and Neuronal Populations in a Model of Par-kinson’s Disease. Brain Stimulation, 10, 1045-1054. [Google Scholar] [CrossRef] [PubMed]
[12] Chen, W., Xiao, Q., Shao, M., et al. (2014) Prevalence of Wear-ing-Off and Dyskinesia among the Patients with Parkinson’s Disease on Levodopa Therapy: A Multi-Center Registry Survey in Mainland China. Translational Neurodegeneration, 3, Article No. 26. [Google Scholar] [CrossRef] [PubMed]
[13] Sarno, M., Gaztanaga, W., Banerjee, N., et al. (2019) Revisiting Eli-gibility for Deep Brain Stimulation: Do Preoperative Mood Symptoms Predict Outcomes in Parkinson’s Disease Pa-tients? Parkinsonism & Related Disorders, 63, 131-136. [Google Scholar] [CrossRef] [PubMed]
[14] Sigurdsson, H.P., Raw, R., Hunter, H., et al. (2021) Nonin-vasive Vagus Nerve Stimulation in Parkinson’s Disease: Current Status and Future Prospects. Expert Review of Medical Devices, 18, 971-984. [Google Scholar] [CrossRef] [PubMed]
[15] Berthoud, H.R. and Neuhuber, W.L. (2000) Functional and Chemical Anatomy of the Afferent Vagal System. Autonomic Neuroscience, 85, 1-17. [Google Scholar] [CrossRef
[16] Cheyuo, C., Jacob, A., Wu, R., Zhou, M., Coppa, G.F. and Wang, P. (2011) The Parasympathetic Nervous System in the Quest for Stroke Therapeutics. Journal of Cerebral Blood Flow & Metabolism, 31, 1187-1195. [Google Scholar] [CrossRef] [PubMed]
[17] Butt, M.F., Albusoda, A., Farmer, A.D. and Aziz, Q. (2019) The Ana-tomical Basis for Transcutaneous Auricular Vagus Nerve Stimulation. Journal of Anatomy, 236, 588-611. [Google Scholar] [CrossRef] [PubMed]
[18] Rhoton Jr., A.L., O’Leary, J.L. and Ferguson, J.P. (1966) The Trigeminal, Facial, Vagal, and Glossopharyngeal Nerves in the Monkey. Afferent Connections. Archives of Neurology, 14, 530-540. [Google Scholar] [CrossRef] [PubMed]
[19] Beckstead, R.M. and Norgren, R. (1979) An Autora-diographic Examination of the Central Distribution of the Trigeminal, Facial, Glossopharyngeal, and Vagal Nerves in the Monkey. Journal of Comparative Neurology, 184, 455-472. [Google Scholar] [CrossRef] [PubMed]
[20] Henry, T.R. (2002) Therapeutic Mechanisms of Vagus Nerve Stimula-tion. Neurology, 59, S3-S14. [Google Scholar] [CrossRef
[21] Kalia, M. and Sullivan, J.M. (1982) Brainstem Projections of Sensory and Motor Components of the Vagus Nerve in the Rat. Journal of Comparative Neurology, 211, 248-265. [Google Scholar] [CrossRef] [PubMed]
[22] Van Bockstaele, E.J., Peoples, J. and Telegan, P. (1999) Efferent Pro-jections of the Nucleus of the Solitary Tract to Peri-Locus Coeruleus Dendrites in Rat Brain: Evidence for a Monosynap-tic Pathway. Journal of Comparative Neurology, 412, 410-428. [Google Scholar] [CrossRef
[23] Levitt, P. and Moore, R.Y. (1978) Noradrenaline Neuron Innervation of the Neocortex in the Rat. Brain Research, 139, 219-231. [Google Scholar] [CrossRef] [PubMed]
[24] Manta, S., Dong, J., Debonnel, G. and Blier, P. (2009) En-hancement of the Function of Rat Serotonin and Norepinephrine Neurons by Sustained Vagus Nerve Stimulation. Jour-nal of Psychiatry & Neuroscience, 34, 272-280.
[25] Ma, J., Qiao, P., Li, Q., et al. (2019) Vagus Nerve Stimulation as a Promising Adjunctive Treatment for Ischemic Stroke. Neurochemistry International, 131, Article 104539. [Google Scholar] [CrossRef] [PubMed]
[26] Jhang, K.A., Lee, E.O., Kim, H.S. and Chong, Y.H. (2014) Norepinephrine Provides Short-Term Neuroprotection against Aβ1-42 by Reducing Oxidative Stress Independent of Nrf2 Activation. Neurobiology of Aging, 35, 2465-2473. [Google Scholar] [CrossRef] [PubMed]
[27] Counts, S.E. and Mufson, E.J. (2010) Noradrenaline Activation of Neurotrophic Pathways Protects against Neuronal Amyloid Toxicity. Journal of Neurochemistry, 113, 649-660. [Google Scholar] [CrossRef] [PubMed]
[28] Florin-Lechner, S.M., Druhan, J.P., Aston-Jones, G. and Valentino, R.J. (1996) Enhanced Norepinephrine Release in Prefrontal Cortex with Burst Stimulation of the Locus Coeruleus. Brain Research, 742, 89-97. [Google Scholar] [CrossRef
[29] Feinstein, D.L., Kalinin, S. and Braun, D. (2016) Causes, Consequences, and Cures for Neuroinflammation Mediated via the Locus Coeruleus: Noradrenergic Signaling System. Journal of Neurochemistry, 139, 154-178. [Google Scholar] [CrossRef] [PubMed]
[30] Coradazzi, M., Gulino, R., Fieramosca, F., Falzacappa, L.V., Riggi, M. and Leanza, G. (2016) Selective Noradrenaline Depletion Impairs Working Memory and Hippocampal Neurogenesis. Neuro-biology of Aging, 48, 93-102. [Google Scholar] [CrossRef] [PubMed]
[31] Marcoli, M., Cervetto, C., Castagnetta, M., Sbaffi, P. and Maura, G. (2004) 5-HT Control of Ischemia-Evoked Glutamate Efflux from Human Cerebrocortical Slices. Neuro-chemistry International, 45, 687-691. [Google Scholar] [CrossRef] [PubMed]
[32] Alenina, N. and Klempin, F. (2015) The Role of Serotonin in Adult Hippocampal Neurogenesis. Behavioural Brain Research, 277, 49-57. [Google Scholar] [CrossRef] [PubMed]
[33] Hosomoto, K., Sasaki, T., Yasuhara, T., et al. (2023) Continuous Vagus Nerve Stimulation Exerts Beneficial Effects on Rats with Experimentally Induced Parkinson’s Disease: Evidence Suggesting Involvement of a Vagal Afferent Pathway. Brain Stimulation, 16, 594-603. [Google Scholar] [CrossRef] [PubMed]
[34] Decker, M.W. and McGaugh, J.L. (1991) The Role of Interactions Between the Cholinergic System and Other Neuromodulatory Systems in Learning and Memory. Synapse, 7, 151-168. [Google Scholar] [CrossRef] [PubMed]
[35] Picciotto, M.R., Higley, M.J. and Mineur, Y.S. (2012) Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior. Neuron, 76, 116-129. [Google Scholar] [CrossRef] [PubMed]
[36] Benarroch, E.E. (1993) The Central Autonomic Network: Func-tional Organization, Dysfunction, and Perspective. Mayo Clinic Proceedings, 68, 988-1001. [Google Scholar] [CrossRef
[37] Pavlov, V.A., Ochani, M., Gallowitsch-Puerta, M., et al. (2006) Central Muscarinic Cholinergic Regulation of the Systemic Inflammatory Response during Endotoxemia. Pro-ceedings of the National Academy of Sciences of the United States of America, 103, 5219-5223. [Google Scholar] [CrossRef] [PubMed]
[38] Borovikova, L.V., Ivanova, S., Zhang, M., et al. (2000) Vagus Nerve Stimulation Attenuates the Systemic Inflammatory Response to Endotoxin. Nature, 405, 458-462. [Google Scholar] [CrossRef] [PubMed]
[39] George, M.S., Sackeim, H.A., Rush, A.J., et al. (2000) Vagus Nerve Stim-ulation: A New Tool for Brain Research and Therapy. Biological Psychiatry, 47, 287-295. [Google Scholar] [CrossRef
[40] Hilz, M.J. (2022) Transcutaneous Vagus Nerve Stimula-tion—A Brief Introduction and Overview. Autonomic Neuroscience, 243, Article 103038. [Google Scholar] [CrossRef] [PubMed]
[41] DeGiorgio, C.M., Schachter, S.C., Handforth, A., et al. (2000) Prospective Long-Term Study of Vagus Nerve Stimulation for the Treatment of Refractory Seizures. Epilepsia, 41, 1195-1200. [Google Scholar] [CrossRef] [PubMed]
[42] Senova, S., Rabu, C., Beaumont, S., et al. (2019) [Vagus Nerve Stimulation and Depression]. La Presse Médicale, 48, 1507-1519. [Google Scholar] [CrossRef] [PubMed]
[43] Giladi, N. and Nieuwboer, A. (2008) Understanding and Treating Freezing of Gait in Parkinsonism, Proposed Working Definition, and Setting the Stage. Movement Disorders, 23, S423-S425. [Google Scholar] [CrossRef] [PubMed]
[44] Marsden, C.D. (1994) Problems with Long-Term Levodopa Therapy for Parkinson’s Disease. Clinical Neuropharmacology, 17, S32-S44.
[45] Nakamura, Y., Yoshinaga, J., Endo, S. and Hikiji, A. (1997) [Multivariate Analysis of the Problems of Long-Term Levodopa Therapy in Parkinson’s Dis-ease]. Rinsho Shinkeigaku, 37, 469-475.
[46] Giladi, N., Kao, R. and Fahn, S. (1997) Freezing Phenomenon in Patients with Parkinsonian Syndromes. Movement Disorders, 12, 302-305. [Google Scholar] [CrossRef] [PubMed]
[47] Macht, M., Kaussner, Y., Möller, J.C., et al. (2007) Predictors of Freezing in Parkinson’s Disease: A Survey of 6,620 Patients. Movement Disorders, 22, 953-956. [Google Scholar] [CrossRef] [PubMed]
[48] Plotnik, M. and Hausdorff, J.M. (2008) The Role of Gait Rhythmicity and Bilateral Coordination of Stepping in the Pathophysiology of Freezing of Gait in Parkinson’s Disease. Movement Disor-ders, 23, S444-450. [Google Scholar] [CrossRef] [PubMed]
[49] Nutt, J.G., Marsden, C.D. and Thompson, P.D. (1993) Human Walking and Higher-Level Gait Disorders, Particularly in the Elderly. Neurology, 43, 268-279. [Google Scholar] [CrossRef
[50] Karachi, C., Grabli, D., Bernard, F.A., et al. (2010) Cholinergic Mes-encephalic Neurons Are Involved in Gait and Postural Disorders in Parkinson Disease. Journal of Clinical Investigation, 120, 2745-2754. [Google Scholar] [CrossRef
[51] Rochester, L., Yarnall, A.J., Baker, M.R., et al. (2012) Cholinergic Dys-function Contributes to Gait Disturbance in Early Parkinson’s Disease. Brain, 135, 2779-2788. [Google Scholar] [CrossRef] [PubMed]
[52] Yarnall, A.J., Rochester, L., Baker, M.R., et al. (2013) Short Latency Afferent Inhibition: A Biomarker for Mild Cognitive Impairment in Parkinson’s Disease? Movement Disorders, 28, 1285-1288. [Google Scholar] [CrossRef] [PubMed]
[53] Bohnen, N.I., Frey, K.A., Studenski, S., et al. (2013) Gait Speed in Parkinson Disease Correlates with Cholinergic Degeneration. Neurology, 81, 1611-1616. [Google Scholar] [CrossRef
[54] Yarnall, A., Rochester, L. and Burn, D.J. (2011) The Inter-play of Cholinergic Function, Attention, and Falls in Parkinson’s Disease. Movement Disorders, 26, 2496-2503. [Google Scholar] [CrossRef] [PubMed]
[55] Jiang, Y., Cao, Z., Ma, H., et al. (2018) Auricular Vagus Nerve Stimula-tion Exerts Antiinflammatory Effects and Immune Regulatory Function in a 6-OHDA Model of Parkinson’s Disease. Neurochemical Research, 43, 2155-2164. [Google Scholar] [CrossRef] [PubMed]
[56] Wang, C., Su, T., Xiao, L., et al. (2022) Right Vagus Nerve Stim-ulation Improves Motor Behavior by Exerting Neuroprotective Effects in Parkinson’s Disease Rats. Annals of Transla-tional Medicine, 10, Article 1314. [Google Scholar] [CrossRef] [PubMed]
[57] Carreno, F.R. and Frazer, A. (2014) Activation of Signaling Pathways Downstream of the Brain-Derived Neurotrophic Factor Receptor, TrkB, in the Rat Brain by Vagal Nerve Stimulation and Antidepressant Drugs. International Journal of Neuropsychopharmacology, 17, 247-258. [Google Scholar] [CrossRef
[58] Furmaga, H., Carreno, F.R. and Frazer, A. (2012) Vagal Nerve Stimulation Rapidly Activates Brain-Derived Neurotrophic Factor Receptor TrkB in Rat Brain. PLOS ONE, 7, E34844. [Google Scholar] [CrossRef] [PubMed]
[59] Fumagalli, F., Racagni, G. and Riva, M.A. (2006) Shedding Light into the Role of BDNF in the Pharmacotherapy of Parkinson’s Disease. The Pharmacogenomics Journal, 6, 95-104. [Google Scholar] [CrossRef] [PubMed]
[60] Baydyuk, M., Nguyen, M.T. and Xu, B. (2011) Chronic Dep-rivation of TrkB Signaling Leads to Selective Late-Onset Nigrostriatal Dopaminergic Degeneration. Experimental Neu-rology, 228, 118-125. [Google Scholar] [CrossRef] [PubMed]
[61] Reichardt, L.F. (2006) Neurotrophin-Regulated Signalling Pathways. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 361, 1545-1564. [Google Scholar] [CrossRef] [PubMed]
[62] Farrand, A.Q., Helke, K.L., Aponte-Cofresí, L., et al. (2019) Effects of Vagus Nerve Stimulation Are Mediated in Part by TrkB in a Parkinson’s Disease Model. Behavioural Brain Research, 373, Article 112080. [Google Scholar] [CrossRef] [PubMed]
[63] Kin, I., Sasaki, T., Yasuhara, T., et al. (2021) Vagus Nerve Stimu-lation with Mild Stimulation Intensity Exerts Anti-Inflammatory and Neuroprotective Effects in Parkinson’s Disease Model Rats. Biomedicines, 9, Article 789. [Google Scholar] [CrossRef] [PubMed]
[64] Farrand, A.Q., Verner, R.S., McGuire, R.M., Helke, K.L., Hinson, V.K. and Boger, H.A. (2020) Differential Effects of Vagus Nerve Stimulation Paradigms Guide Clinical Devel-opment for Parkinson’s Disease. Brain Stimulation, 13, 1323-1332. [Google Scholar] [CrossRef] [PubMed]
[65] Morris, R., Yarnall, A.J., Hunter, H., Taylor, J.P., Baker, M.R. and Rochester, L. (2019) Noninvasive Vagus Nerve Stimulation to Target Gait Impairment in Parkinson’s Disease. Move-ment Disorders, 34, 918-919. [Google Scholar] [CrossRef] [PubMed]
[66] Mondal, B., Choudhury, S., Simon, B., Baker, M.R. and Kumar, H. (2019) Noninvasive Vagus Nerve Stimulation Improves Gait and Reduces Freezing of Gait in Parkinson’s Disease. Movement Disorders, 34, 917-918. [Google Scholar] [CrossRef] [PubMed]
[67] Mondal, B., Choudhury, S., Banerjee, R., et al. (2022) Retraction Note: Non-Invasive Vagus Nerve Stimulation Improves Clinical and Molecular Biomarkers of Parkinson’s Disease in Patients with Freezing of Gait. NPJ Parkinson’s Disease, 8, Article No. 148. [Google Scholar] [CrossRef] [PubMed]
[68] Marano, M., Anzini, G., Musumeci, G., et al. (2022) Transcuta-neous Auricular Vagus Stimulation Improves Gait and Reaction Time in Parkinson’s Disease. Movement Disorders, 37, 2163-2164. [Google Scholar] [CrossRef] [PubMed]
[69] Zhang, H., Cao, X.Y., Wang, L.N., et al. (2023) Transcutane-ous Auricular Vagus Nerve Stimulation Improves Gait and Cortical Activity in Parkinson’s Disease: A Pilot Randomized Study. CNS Neuroscience & Therapeutics, 29, 3889-3900. [Google Scholar] [CrossRef] [PubMed]
[70] Lench, D.H., Turner, T.H., McLeod, C., et al. (2023) Multi-Session Transcutaneous Auricular Vagus Nerve Stimulation for Parkinson’s Disease: Evaluating Feasibility, Safety, and Prelimi-nary Efficacy. Frontiers in Neurology, 14, Article 1210103. [Google Scholar] [CrossRef] [PubMed]
[71] Aarsland, D., Kramberger, M.G., Korczyn, A.D., Reichmann, H. and Chaudhuri, K.R. (2015) Neuropsychiatric Symptoms in Parkinson’s Disease. Journal of Parkinson’s Disease, 5, 659-667. [Google Scholar] [CrossRef
[72] Chaudhuri, K.R. and Schapira, A.H. (2009) Non-Motor Symptoms of Parkinson’s Disease: Dopaminergic Pathophysiology and Treatment. The Lancet Neurology, 8, 464-474. [Google Scholar] [CrossRef
[73] Faivre, F., Joshi, A., Bezard, E. and Barrot, M. (2019) The Hidden Side of Parkinson’s Disease: Studying Pain, Anxiety and Depression in Animal Models. Neuroscience & Bi-obehavioral Reviews, 96, 335-352. [Google Scholar] [CrossRef] [PubMed]
[74] Follesa, P., Biggio, F., Gorini, G., et al. (2007) Vagus Nerve Stimulation Increases Norepinephrine Concentration and the Gene Expression of BDNF and BFGF in the Rat Brain. Brain Research, 1179, 28-34. [Google Scholar] [CrossRef] [PubMed]
[75] Weise, D., Adamidis, M., Pizzolato, F., Rumpf, J.J., Fricke, C. and Classen, J. (2015) Assessment of Brainstem Function with Auricular Branch of Vagus Nerve Stimulation in Parkin-son’s Disease. PLOS ONE, 10, E0120786. [Google Scholar] [CrossRef] [PubMed]
[76] Carreno, F.R. and Frazer, A. (2017) Vagal Nerve Stimulation for Treatment-Resistant Depression. Neurotherapeutics, 14, 716-727. [Google Scholar] [CrossRef] [PubMed]
[77] Hein, E., Nowak, M., Kiess, O., et al. (2013) Auricular Transcutaneous Electrical Nerve Stimulation in Depressed Patients: A Randomized Controlled Pilot Study. Journal of Neural Transmission (Vienna), 120, 821-827. [Google Scholar] [CrossRef] [PubMed]
[78] Rong, P., Liu, J., Wang, L., et al. (2016) Effect of Transcutaneous Auricular Vagus Nerve Stimulation on Major Depressive Disorder: A Nonrandomized Controlled Pilot Study. Journal of Affective Disorders, 195, 172-179. [Google Scholar] [CrossRef] [PubMed]
[79] George, M.S., Ward Jr., H.E., Ninan, P.T., et al. (2008) A Pilot Study of Vagus Nerve Stimulation (VNS) for Treatment-Resistant Anxiety Disorders. Brain Stimulation, 1, 112-121. [Google Scholar] [CrossRef] [PubMed]
[80] Burger, A.M., Van der Does, W., Thayer, J.F., Brosschot, J.F. and Verkuil, B. (2019) Transcutaneous Vagus Nerve Stimulation Reduces Spontaneous but Not Induced Negative Thought Intrusions in High Worriers. Biological Psychology, 142, 80-89. [Google Scholar] [CrossRef] [PubMed]
[81] Kamel, L.Y., Xiong, W., Gott, B.M., Kumar, A. and Con-way, C.R. (2022) Vagus Nerve Stimulation: An Update on a Novel Treatment for Treatment-Resistant Depression. Journal of the Neurological Sciences, 434, Article 120171. [Google Scholar] [CrossRef] [PubMed]
[82] Lesser, G.T. (2002) Frequency of Bowel Movements and Future Risk of Parkinson’s Disease. Neurology, 58, 838-839; Author Reply 838-839. [Google Scholar] [CrossRef
[83] Braak, H., de Vos, R.A., Bohl, J. and Del Tredici, K. (2006) Gastric Alpha-Synuclein Immunoreactive Inclusions in Meissner’s and Auerbach’s Plexuses in Cases Staged for Parkinson’s Disease-Related Brain Pathology. Neuroscience Letters, 396, 67-72. [Google Scholar] [CrossRef] [PubMed]
[84] Wakabayashi, K., Takahashi, H., Takeda, S., Ohama, E. and Iku-ta, F. (1988) Parkinson’s Disease: The Presence of Lewy Bodies in Auerbach’s and Meissner’s Plexuses. Acta Neuro-pathologica, 76, 217-221. [Google Scholar] [CrossRef
[85] Ekblad, E., Mulder, H. and Sundler, F. (1996) Vasoactive Intestinal Pep-tide Expression in Enteric Neurons Is Upregulated by Both Colchicine and Axotomy. Regulatory Peptides, 63, 113-121. [Google Scholar] [CrossRef] [PubMed]
[86] Li, Z.S., Pham, T.D., Tamir, H., Chen, J.J. and Gershon, M.D. (2004) Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation. Journal of Neuroscience, 24, 1330-1339. [Google Scholar] [CrossRef
[87] Luck, M.S., Dahl, J.L., Boyeson, M.G. and Bass, P. (1993) Neuroplasticity in the Smooth Muscle of the Myenterically and Extrinsically Denervated Rat Jejunum. Cell and Tissue Research, 271, 363-374. [Google Scholar] [CrossRef
[88] Hopkins, D.A., Bieger, D., deVente, J. and Steinbusch, W.M. (1996) Vagal Efferent Projections: Viscerotopy, Neurochemistry and Effects of Vagotomy. Progress in Brain Research, 107, 79-96. [Google Scholar] [CrossRef
[89] Braak, H., Del Tredici, K., Rüb, U., de Vos, R.A., Jansen Steur, E.N. and Braak, E. (2003) Staging of Brain Pathology Related to Sporadic Parkinson’s Disease. Neurobiology of Aging, 24, 197-211. [Google Scholar] [CrossRef
[90] Zheng, Z. and Travagli, R.A. (2007) Dopamine Effects on Identified Rat Vagal Motoneurons. American Journal of Physiology-Gastrointestinal and Liver Physiology, 292, G1002-1008. [Google Scholar] [CrossRef] [PubMed]
[91] Paulon, E., Nastou, D., Jaboli, F., Marin, J., Liebler, E. and Epstein, O. (2017) Proof of Concept: Short-Term Non-Invasive Cervical Vagus Nerve Stimulation in Patients with Drug-Refractory Gastroparesis. Frontline Gastroenterology, 8, 325-330. [Google Scholar] [CrossRef] [PubMed]
[92] Gottfried-Blackmore, A., Adler, E.P., Fernandez-Becker, N., Clarke, J., Habtezion, A. and Nguyen, L. (2020) Open-Label Pilot Study: Non-Invasive Vagal Nerve Stimulation Im-proves Symptoms and Gastric Emptying in Patients with Idiopathic Gastroparesis. Neurogastroenterology & Motility, 32, E13769. [Google Scholar] [CrossRef] [PubMed]
[93] Hely, M.A., Reid, W.G., Adena, M.A., Halliday, G.M. and Mor-ris, J.G. (2008) The Sydney Multicenter Study of Parkinson’s Disease: The Inevitability of Dementia at 20 Years. Movement Disorders, 23, 837-844. [Google Scholar] [CrossRef] [PubMed]
[94] Buter, T.C., Van Den Hout, A., Matthews, F.E., Larsen, J.P., Brayne, C. and Aarsland, D. (2008) Dementia and Survival in Parkinson Disease: A 12-Year Population Study. Neurology, 70, 1017-1022. [Google Scholar] [CrossRef] [PubMed]
[95] Yarnall, A.J., Breen, D.P., Duncan, G.W., et al. (2014) Characterizing Mild Cognitive Impairment in Incident Parkinson Disease: The ICICLE-PD Study. Neurology, 82, 308-316. [Google Scholar] [CrossRef
[96] Šimko, P., Kent, J.A. and Rektorova, I. (2022) Is Non-Invasive Brain Stimulation Effective for Cognitive Enhancement in Alzheimer’s Disease? An Updated Me-ta-Analysis. Clinical Neurophysiology, 144, 23-40. [Google Scholar] [CrossRef] [PubMed]
[97] Sjögren, M.J., Hellström, P.T., Jonsson, M.A., Runnerstam, M., Silander, H.C. and Ben-Menachem, E. (2002) Cognition-Enhancing Effect of Vagus Nerve Stimulation in Patients with Alzheimer’s Disease: A Pilot Study. Journal of Clinical Psychiatry, 63, 972-980. [Google Scholar] [CrossRef
[98] Merrill, C.A., Jonsson, M.A., Minthon, L., et al. (2006) Vagus Nerve Stimulation in Patients with Alzheimer’s Disease: Additional Follow-Up Results of A Pilot Study through 1 Year. Jour-nal of Clinical Psychiatry, 67, 1171-1178. [Google Scholar] [CrossRef
[99] Kalf, J.G., De Swart, B.J., Bloem, B.R. and Munneke, M. (2012) Prevalence of Oropharyngeal Dysphagia in Parkinson’s Disease: A Meta-Analysis. Parkinsonism & Related Disorders, 18, 311-315. [Google Scholar] [CrossRef] [PubMed]
[100] Leta, V., Klingelhoefer, L., Longardner, K., et al. (2023) Gas-trointestinal Barriers to Levodopa Transport and Absorption in Parkinson’s Disease. European Journal of Neurology, 30, 1465-1480. [Google Scholar] [CrossRef] [PubMed]