{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T16:03:46Z","timestamp":1760976226422,"version":"build-2065373602"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T00:00:00Z","timestamp":1641859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Prinses Beatrix Fonds","award":["War05-0203"],"award-info":[{"award-number":["War05-0203"]}]},{"name":"Parkinsonvereniging","award":["2011-V04"],"award-info":[{"award-number":["2011-V04"]}]},{"name":"Stichting Internationaal Parkinsonfonds","award":["n.a."],"award-info":[{"award-number":["n.a."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>There is a growing interest in deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) as a potential therapeutic modality for Parkinson\u2019s disease dementia (PDD). Low-frequency stimulation has yielded encouraging results in individual patients; however, these are not yet sustained in larger studies. With the aim to expand the understanding of NBM-DBS, we share our experience with serendipitous NBM-DBS in patients treated with DBS of the internal Globus pallidus (GPi) for Parkinson\u2019s disease. Since NBM is anatomically located ventral to GPi, several GPi-treated patients appeared to have the distal contact of DBS-electrode(s) positioned in the NBM. We hypothesized that unintentional high-frequency NBM-DBS over a period of one year would result in the opposite effect of low-frequency NBM-stimulation and cause cognitive decline. We studied a cohort of 33 patients with bilateral high-frequency DBS in the GPi for Parkinson\u2019s disease, of which twelve were unintentionally co-stimulated in NBM. The subgroups of unintentional unilateral (N = 7) and bilateral NBM-DBS (N = 5) were compared to the control group of bilateral GPi-DBS (N = 11). Here, we show that unintentional high-frequency NBM-DBS did not cause a significantly faster decline in cognitive function. Further research is warranted for characterizing the therapeutic role of NBM-DBS.<\/jats:p>","DOI":"10.3390\/jcm11020337","type":"journal-article","created":{"date-parts":[[2022,1,11]],"date-time":"2022-01-11T14:05:07Z","timestamp":1641909907000},"page":"337","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Serendipitous Stimulation of Nucleus Basalis of Meynert\u2014The Effect of Unintentional, Long-Term High-Frequency Stimulation on Cognition in Parkinson\u2019s Disease"],"prefix":"10.3390","volume":"11","author":[{"given":"I. Daria","family":"Bogdan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. L. Marinus","family":"Oterdoom","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teus","family":"van Laar","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rients B.","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent J.","family":"Odekerken","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam Neuroscience Institute, Amsterdam University Medical Center, 1105 Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith A.","family":"Boel","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam Neuroscience Institute, Amsterdam University Medical Center, 1105 Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob M. A.","family":"de Bie","sequence":"additional","affiliation":[{"name":"Department of Neurology, Amsterdam Neuroscience Institute, Amsterdam University Medical Center, 1105 Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0814-5680","authenticated-orcid":false,"given":"J. Marc C.","family":"van Dijk","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Medical Center Groningen, University of Groningen, 9713 Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"on behalf of the NSTAPS Study Group","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,11]]},"reference":[{"key":"ref_1","first-page":"S3","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. Park. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.jns.2009.08.034","article-title":"The epidemiology of dementia associated with Parkinson disease","volume":"289","author":"Aarsland","year":"2010","journal-title":"J. Neurol. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1212\/01.wnl.0000306632.43729.24","article-title":"Dementia and survival in Parkinson disease: A 12-year population study","volume":"70","author":"Buter","year":"2008","journal-title":"Neurology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.1002\/mds.21507","article-title":"Clinical diagnostic criteria for dementia associated with Parkinson\u2019s disease","volume":"22","author":"Emre","year":"2007","journal-title":"Mov. Disord."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1159\/000101130","article-title":"Stimulation of the Basal Nucleus of Meynert in Senile Dementia of Alzheimer\u2019s Type","volume":"48","author":"Turnbull","year":"1985","journal-title":"Ster. Funct. Neurosurg."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1454","DOI":"10.1093\/brain\/awv104","article-title":"Parkinson\u2019s disease dementia: A neural networks perspective","volume":"138","author":"Gratwicke","year":"2015","journal-title":"Brain"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2676","DOI":"10.1016\/j.neubiorev.2013.09.003","article-title":"The nucleus basalis of Meynert: A new target for deep brain stimulation in dementia?","volume":"37","author":"Gratwicke","year":"2013","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.neurobiolaging.2010.11.015","article-title":"Volumetric analysis of the substantia innominata in patients with Parkinson\u2019s disease according to cognitive status","volume":"33","author":"Choi","year":"2012","journal-title":"Neurobiol. Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1001\/archneurol.2009.102","article-title":"Cognitive Functions in a Patient With Parkinson-Dementia Syndrome Undergoing Deep Brain Stimulation","volume":"66","author":"Freund","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/mp.2014.32","article-title":"Deep brain stimulation of the nucleus basalis of Meynert in Alzheimer\u2019s dementia","volume":"20","author":"Kuhn","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1001\/jamaneurol.2017.3762","article-title":"Bilateral deep brain stimulation of the nucleus basalis of meynert for Parkinson disease dementia a randomized clinical trial","volume":"75","author":"Gratwicke","year":"2018","journal-title":"JAMA Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1159\/000493094","article-title":"Simultaneous Stimulation of the Globus Pallidus Interna and the Nucleus Basalis of Meynert in the Parkinson-Dementia Syndrome","volume":"47","author":"Nombela","year":"2019","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.brs.2020.04.010","article-title":"Bilateral nucleus basalis of Meynert deep brain stimulation for dementia with Lewy bodies: A randomised clinical trial","volume":"13","author":"Gratwicke","year":"2020","journal-title":"Brain Stimul."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"645584","DOI":"10.3389\/fnhum.2021.645584","article-title":"Case Report: Deep Brain Stimulation of the Nucleus Basalis of Meynert for Advanced Alzheimer\u2019s Disease","volume":"15","author":"Zhang","year":"2021","journal-title":"Front. Hum. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0079-6123(08)60908-5","article-title":"Chapter 26 Human brain cholinergic pathways","volume":"84","author":"Mesulam","year":"1990","journal-title":"Prog. Brain Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Bogdan, I.D., Van Laar, T., Oterdoom, D.M., Drost, G., Van Dijk, J.M.C., and Beudel, M. (2020). Optimal Parameters of Deep Brain Stimulation in Essential Tremor: A Meta-Analysis and Novel Programming Strategy. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061855"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1001\/jamapsychiatry.2016.0152","article-title":"Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression","volume":"73","author":"Bergfeld","year":"2016","journal-title":"JAMA Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.brs.2016.05.013","article-title":"Deep Brain Stimulation of the Nucleus Basalis of Meynert in Alzheimer\u2019s Dementia: Potential Predictors of Cognitive Change and Results of a Long-Term Follow-Up in Eight Patients","volume":"9","author":"Hardenacke","year":"2016","journal-title":"Brain Stimul."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1137","DOI":"10.1097\/00001756-200405190-00011","article-title":"Deep brain stimulation creates an informational lesion of the stimulated nucleus","volume":"15","author":"Grill","year":"2004","journal-title":"NeuroReport"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1152\/jn.00103.2010","article-title":"Deep Brain Stimulation Alleviates Parkinsonian Bradykinesia by Regularizing Pallidal Activity","volume":"104","author":"Dorval","year":"2010","journal-title":"J. Neurophysiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2640","DOI":"10.1016\/j.cub.2017.07.021","article-title":"Intermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys","volume":"27","author":"Liu","year":"2017","journal-title":"Curr. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S1474-4422(12)70264-8","article-title":"Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson\u2019s disease (NSTAPS study): A randomised controlled trial","volume":"12","author":"Odekerken","year":"2013","journal-title":"Lancet Neurol."},{"key":"ref_23","unstructured":"Schaltenbrand, W. (2020, July 10). Neurosurgery|Atlas for Stereotaxy of the Human Brain. Available online: https:\/\/www.thieme.com\/books-main\/neurosurgery\/product\/168-atlas-for-stereotaxy-of-the-human-brain."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1017\/S1092852916000286","article-title":"The medial forebrain bundle as a target for deep brain stimulation for obsessive-compulsive disorder","volume":"22","author":"Coenen","year":"2016","journal-title":"CNS Spectr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3389\/fnint.2012.00015","article-title":"\u201cConnectomic surgery\u201d: Diffusion tensor imaging (DTI) tractography as a targeting modality for surgical modulation of neural networks","volume":"6","author":"Henderson","year":"2012","journal-title":"Front. Integr. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3389\/fnagi.2017.00047","article-title":"White Matter Damage in the Cholinergic System Contributes to Cognitive Impairment in Subcortical Vascular Cognitive Impairment, No Dementia","volume":"9","author":"Liu","year":"2017","journal-title":"Front. Aging Neurosci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"116607","DOI":"10.1016\/j.neuroimage.2020.116607","article-title":"Cholinergic white matter pathways make a stronger contribution to attention and memory in normal aging than cerebrovascular health and nucleus basalis of Meynert","volume":"211","author":"Nemy","year":"2020","journal-title":"NeuroImage"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2249","DOI":"10.1093\/brain\/121.12.2249","article-title":"Trajectories of cholinergic pathways within the cerebral hemispheres of the human brain","volume":"121","author":"Selden","year":"1998","journal-title":"Brain"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1002\/hbm.24417","article-title":"The corticotopic organization of the human basal forebrain as revealed by regionally selective functional connectivity profiles","volume":"40","author":"Fritz","year":"2019","journal-title":"Hum. Brain Mapp."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1016\/j.biopsych.2019.01.017","article-title":"A Randomized Trial Directly Comparing Ventral Capsule and Anteromedial Subthalamic Nucleus Stimulation in Obsessive-Compulsive Disorder: Clinical and Imaging Evidence for Dissociable Effects","volume":"85","author":"Tyagi","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.parkreldis.2018.03.024","article-title":"Oscillatory activity and cortical coherence of the nucleus basalis of Meynert in Parkinson\u2019s disease dementia","volume":"52","author":"Nazmuddin","year":"2018","journal-title":"Park. Relat. Disord."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1001\/jamapsychiatry.2019.0740","article-title":"Targeting Cognition and Networks Through Neural Oscillations: Next-Generation Clinical Brain Stimulation","volume":"76","author":"Widge","year":"2019","journal-title":"JAMA Psychiatry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.neuron.2018.09.023","article-title":"Working Memory 2.0","volume":"100","author":"Miller","year":"2018","journal-title":"Neuron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1696","DOI":"10.1038\/s41591-021-01480-w","article-title":"Closed-loop neuromodulation in an individual with treatment-resistant depression","volume":"27","author":"Scangos","year":"2021","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Basu, I., Yousefi, A., Crocker, B., Zelmann, R., Paulk, A.C., Peled, N., Ellard, K.K., Weisholtz, D.S., Cosgrove, G.R., and Deckersbach, T. (2021). Closed-loop enhancement and neural decoding of cognitive control in humans. Nat. Biomed. Eng., 1\u201313.","DOI":"10.1101\/2020.04.24.059964"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.brs.2016.12.012","article-title":"Being open minded about neuromodulation trials: Finding success in our \u201cfailures\u201d","volume":"10","author":"Fins","year":"2017","journal-title":"Brain Stimul."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Richardson, H.S. (2012). Moral Entanglements: The Ancillary-Care Obligations of Medical Researchers, Oxford University Press. Available online: https:\/\/books.google.com\/books\/about\/Moral_Entanglements.html?id=2J9pAgAAQBAJ.","DOI":"10.1093\/acprof:oso\/9780195388930.001.0001"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.neuroimage.2018.01.015","article-title":"Quantifying axonal responses in patient-specific models of subthalamic deep brain stimulation","volume":"172","author":"Gunalan","year":"2018","journal-title":"NeuroImage"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/2\/337\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:27:09Z","timestamp":1760362029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/2\/337"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,11]]},"references-count":38,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["jcm11020337"],"URL":"https:\/\/doi.org\/10.3390\/jcm11020337","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2022,1,11]]}}}