{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T10:36:52Z","timestamp":1790937412485,"version":"4.1.0"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Interdisziplin\u00e4res Zentrum f\u00fcr Klinische Forschung, University Hospital Wuerzburg","award":["Z-3\/64-2"],"award-info":[{"award-number":["Z-3\/64-2"]}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Academy of Finland, Finnish Medical Foundation"},{"DOI":"10.13039\/100016238","name":"The Finnish Foundation for Alcohol Studies","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016238","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Instrumentarium Research Foundation"},{"name":"Finnish Parkinson Foundation"},{"DOI":"10.13039\/100007429","name":"Nancy Lurie Marks Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007429","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kaye Family Research Endowment"},{"name":"Ellison\/Baszucki Foundation"},{"name":"NIH","award":["R01MH113929"],"award-info":[{"award-number":["R01MH113929"]}]},{"name":"NIH","award":["R21MH126271"],"award-info":[{"award-number":["R21MH126271"]}]},{"name":"NIH","award":["R56AG069086"],"award-info":[{"award-number":["R56AG069086"]}]},{"name":"NIH","award":["R01MH115949"],"award-info":[{"award-number":["R01MH115949"]}]},{"name":"NIH","award":["R01AG060987"],"award-info":[{"award-number":["R01AG060987"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,5,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Deep brain stimulation is an effective treatment for Parkinson\u2019s disease but can be complicated by side-effects such as cognitive decline. There is often a delay before this side-effect is apparent and the mechanism is unknown, making it difficult to identify patients at risk or select appropriate deep brain stimulation settings. Here, we test whether connectivity between the stimulation site and other brain regions is associated with cognitive decline following deep brain stimulation. First, we studied a unique patient cohort with cognitive decline following subthalamic deep brain stimulation for Parkinson\u2019s disease (n = 10) where reprogramming relieved the side-effect without loss of motor benefit. Using resting state functional connectivity data from a large normative cohort (n = 1000), we computed connectivity between each stimulation site and the subiculum, an a priori brain region functionally connected to brain lesions causing memory impairment. Connectivity between deep brain stimulation sites and this same subiculum region was significantly associated with deep brain stimulation induced cognitive decline (P &amp;lt; 0.02).<\/jats:p>\n                  <jats:p>We next performed a data-driven analysis to identify connections most associated with deep brain stimulation induced cognitive decline. Deep brain stimulation sites causing cognitive decline (versus those that did not) were more connected to the anterior cingulate, caudate nucleus, hippocampus, and cognitive regions of the cerebellum (PFWE &amp;lt; 0.05). The spatial topography of this deep brain stimulation-based circuit for cognitive decline aligned with an a priori lesion-based circuit for memory impairment (P = 0.017). To begin translating these results into a clinical tool that might be used for deep brain stimulation programming, we generated a \u2018heat map\u2019 in which the intensity of each voxel reflects the connectivity to our cognitive decline circuit. We then validated this heat map using an independent dataset of Parkinson\u2019s disease patients in which cognitive performance was measured following subthalamic deep brain stimulation (n = 33). Intersection of deep brain stimulation sites with our heat map was correlated with changes in the Mattis dementia rating scale 1 year after lead implantation (r = 0.39; P = 0.028).<\/jats:p>\n                  <jats:p>Finally, to illustrate how this heat map might be used in clinical practice, we present a case that was flagged as \u2018high risk\u2019 for cognitive decline based on intersection of the patient\u2019s deep brain stimulation site with our heat map. This patient had indeed experienced cognitive decline and our heat map was used to select alternative deep brain stimulation parameters. At 14 days follow-up the patient\u2019s cognition improved without loss of motor benefit. These results lend insight into the mechanism of deep brain stimulation induced cognitive decline and suggest that connectivity-based heat maps may help identify patients at risk and who might benefit from deep brain stimulation reprogramming.<\/jats:p>","DOI":"10.1093\/brain\/awac012","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T10:37:59Z","timestamp":1641983879000},"page":"1410-1421","source":"Crossref","is-referenced-by-count":100,"title":["A brain network for deep brain stimulation induced cognitive decline in Parkinson\u2019s disease"],"prefix":"10.1093","volume":"145","author":[{"given":"Martin M.","family":"Reich","sequence":"first","affiliation":[{"name":"Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Department of Neurology, University Hospital and Julius-Maximilians-University, Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joey","family":"Hsu","sequence":"additional","affiliation":[{"name":"Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ferguson","sequence":"additional","affiliation":[{"name":"Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Center for Brain Circuit Therapeutics, Department of Neurology, Psychiatry, and Radiology, Brigham & Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic L. W. V. J.","family":"Schaper","sequence":"additional","affiliation":[{"name":"Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"},{"name":"Harvard Medical School, Boston, MA, USA"},{"name":"Center for Brain Circuit Therapeutics, Department of Neurology, Psychiatry, and Radiology, Brigham & Women\u2019s Hospital, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3457-9415","authenticated-orcid":false,"given":"Juho","family":"Joutsa","sequence":"additional","affiliation":[{"name":"Berenson-Allen Center for Noninvasive Brain Stimulation and Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA"},{"name":"Turku Brain and Mind Center, Clinical Neurosciences, University of Turku, Turku, Finland"},{"name":"Turku PET Centre, Neurocenter, Turku University Hospital, Turku, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas","family":"Roothans","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital and Julius-Maximilians-University, Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Nickl","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University Hospital and Julius-Maximilians-University, Wuerzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0724-8087","authenticated-orcid":false,"given":"Anneke","family":"Frankemolle-Gilbert","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Duke University, Durham, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Alberts","sequence":"additional","affiliation":[{"name":"Department 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