Emily Lecy, Maria E Linn-Evans, Sommer L Amundsen-Huffmaster, Tara Palnitkar, Remi Patriat, Jae Woo Chung, Angela M Noecker, Michael C Park, Cameron C McIntyre, Jerrold L Vitek, Scott E Cooper, Noam Harel, Matthew D Johnson, Colum D MacKinnon
{"title":"Neural pathways associated with reduced rigidity during pallidal deep brain stimulation for Parkinson's disease.","authors":"Emily Lecy, Maria E Linn-Evans, Sommer L Amundsen-Huffmaster, Tara Palnitkar, Remi Patriat, Jae Woo Chung, Angela M Noecker, Michael C Park, Cameron C McIntyre, Jerrold L Vitek, Scott E Cooper, Noam Harel, Matthew D Johnson, Colum D MacKinnon","doi":"10.1152/jn.00155.2024","DOIUrl":null,"url":null,"abstract":"<p><p>Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity (<i>P</i> < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output.<b>NEW & NOTEWORTHY</b> Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.</p>","PeriodicalId":16563,"journal":{"name":"Journal of neurophysiology","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11427047/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of neurophysiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1152/jn.00155.2024","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/7 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Deep brain stimulation (DBS) of the internal segment of the globus pallidus (GPi) can markedly reduce muscle rigidity in people with Parkinson's disease (PD); however, the mechanisms mediating this effect are poorly understood. Computational modeling of DBS provides a method to estimate the relative contributions of neural pathway activations to changes in outcomes. In this study, we generated subject-specific biophysical models of GPi DBS (derived from individual 7-T MRI), including pallidal efferent, putamenal efferent, and internal capsule pathways, to investigate how activation of neural pathways contributed to changes in forearm rigidity in PD. Ten individuals (17 arms) were tested off medication under four conditions: off stimulation, on clinically optimized stimulation, and on stimulation specifically targeting the dorsal GPi or ventral GPi. Quantitative measures of forearm rigidity, with and without a contralateral activation maneuver, were obtained with a robotic manipulandum. Clinically optimized GPi DBS settings significantly reduced forearm rigidity (P < 0.001), which aligned with GPi efferent fiber activation. The model demonstrated that GPi efferent axons could be activated at any location along the GPi dorsal-ventral axis. These results provide evidence that rigidity reduction produced by GPi DBS is mediated by preferential activation of GPi efferents to the thalamus, likely leading to a reduction in excitability of the muscle stretch reflex via overdriving pallidofugal output.NEW & NOTEWORTHY Subject-specific computational models of pallidal deep brain stimulation, in conjunction with quantitative measures of forearm rigidity, were used to examine the neural pathways mediating stimulation-induced changes in rigidity in people with Parkinson's disease. The model uniquely included internal, efferent and adjacent pathways of the basal ganglia. The results demonstrate that reductions in rigidity evoked by deep brain stimulation were principally mediated by the activation of globus pallidus internus efferent pathways.
期刊介绍:
The Journal of Neurophysiology publishes original articles on the function of the nervous system. All levels of function are included, from the membrane and cell to systems and behavior. Experimental approaches include molecular neurobiology, cell culture and slice preparations, membrane physiology, developmental neurobiology, functional neuroanatomy, neurochemistry, neuropharmacology, systems electrophysiology, imaging and mapping techniques, and behavioral analysis. Experimental preparations may be invertebrate or vertebrate species, including humans. Theoretical studies are acceptable if they are tied closely to the interpretation of experimental data and elucidate principles of broad interest.