Artur Vetkas , Srdjan Sumarac , Samantha Chau , Reese Clinton , Emily Haniff , Alexandre Boutet , Can Sarica , Xilin Liu , Mojgan Hodaie , Taufik A. Valiante , Suneil K. Kalia , Andres M. Lozano , William D. Hutchison , Luka Milosevic
{"title":"颅内刺激对人局部神经血管反应的影响。","authors":"Artur Vetkas , Srdjan Sumarac , Samantha Chau , Reese Clinton , Emily Haniff , Alexandre Boutet , Can Sarica , Xilin Liu , Mojgan Hodaie , Taufik A. Valiante , Suneil K. Kalia , Andres M. Lozano , William D. Hutchison , Luka Milosevic","doi":"10.1016/j.brs.2025.09.018","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Deep brain stimulation (DBS) is used to treat neurological and psychiatric disorders by modulating neuronal circuits. However, the effects of electrical stimulation on the neurovascular unit remain poorly understood due to limitations of capturing microvascular changes near implanted leads. This motivated us to investigate the cardioballistic waveform (CBW) as an electrophysiological surrogate of vascular dynamics in response to microstimulation.</div></div><div><h3>Methods</h3><div>Microelectrode recordings (n = 193; 108 patients) were obtained during DBS implantation surgery from two electrodes (∼600 μm apart) before and after microstimulation through one electrode. Generalized linear mixed models assessed CBW amplitude changes following 1 Hz or 100 Hz stimulation across basal ganglia regions and white matter. Neuronal activity was also analyzed, including phase-locking to the cardiac cycle, firing rates and patterns, and micro-LFP features. An analytical model interpreted CBW amplitudes as pressure-driven vessel wall expansion, enabling estimation of stimulation-evoked vasodilation and cerebral blood flow.</div></div><div><h3>Results</h3><div>CBW amplitudes increased significantly after 100 Hz stimulation at the stimulating electrode, but not at the non-stimulating electrode or after 1 Hz stimulation. Significant region-specific effects were observed in the ventral intermediate nucleus (Vim; 107 ± 13 %), subthalamic nucleus (STN; 79 ± 7 %), and globus pallidus internus (GPi; 78 ± 8 %), but not in white matter (WM; 50 ± 14 %) or substantia nigra pars reticulata (SNr; 45 ± 8 %). Across 50 recorded single units, 18 (36 %) were phase-locked to the cardiac cycle, but stimulation did not alter phase-locking value, and changes in spiking or micro-LFP features before versus after stimulation did not scale with CBW changes. Modelling showed that the mean 88 % CBW increase across Vim, STN, and GPi corresponds to an acute increase in cerebral blood flow.</div></div><div><h3>Conclusion</h3><div>CBW recordings reveal that high-frequency DBS evokes region-specific vascular responses which can be modeled as substantial increases in local blood flow, establishing CBW amplitude as a potential biomarker of subcortical hemodynamics, and a potential therapeutic modality.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 6","pages":"Pages 1810-1820"},"PeriodicalIF":8.4000,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The effects of intracranial stimulation on local neurovascular responses in humans\",\"authors\":\"Artur Vetkas , Srdjan Sumarac , Samantha Chau , Reese Clinton , Emily Haniff , Alexandre Boutet , Can Sarica , Xilin Liu , Mojgan Hodaie , Taufik A. Valiante , Suneil K. Kalia , Andres M. Lozano , William D. Hutchison , Luka Milosevic\",\"doi\":\"10.1016/j.brs.2025.09.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Deep brain stimulation (DBS) is used to treat neurological and psychiatric disorders by modulating neuronal circuits. However, the effects of electrical stimulation on the neurovascular unit remain poorly understood due to limitations of capturing microvascular changes near implanted leads. This motivated us to investigate the cardioballistic waveform (CBW) as an electrophysiological surrogate of vascular dynamics in response to microstimulation.</div></div><div><h3>Methods</h3><div>Microelectrode recordings (n = 193; 108 patients) were obtained during DBS implantation surgery from two electrodes (∼600 μm apart) before and after microstimulation through one electrode. Generalized linear mixed models assessed CBW amplitude changes following 1 Hz or 100 Hz stimulation across basal ganglia regions and white matter. Neuronal activity was also analyzed, including phase-locking to the cardiac cycle, firing rates and patterns, and micro-LFP features. An analytical model interpreted CBW amplitudes as pressure-driven vessel wall expansion, enabling estimation of stimulation-evoked vasodilation and cerebral blood flow.</div></div><div><h3>Results</h3><div>CBW amplitudes increased significantly after 100 Hz stimulation at the stimulating electrode, but not at the non-stimulating electrode or after 1 Hz stimulation. Significant region-specific effects were observed in the ventral intermediate nucleus (Vim; 107 ± 13 %), subthalamic nucleus (STN; 79 ± 7 %), and globus pallidus internus (GPi; 78 ± 8 %), but not in white matter (WM; 50 ± 14 %) or substantia nigra pars reticulata (SNr; 45 ± 8 %). Across 50 recorded single units, 18 (36 %) were phase-locked to the cardiac cycle, but stimulation did not alter phase-locking value, and changes in spiking or micro-LFP features before versus after stimulation did not scale with CBW changes. Modelling showed that the mean 88 % CBW increase across Vim, STN, and GPi corresponds to an acute increase in cerebral blood flow.</div></div><div><h3>Conclusion</h3><div>CBW recordings reveal that high-frequency DBS evokes region-specific vascular responses which can be modeled as substantial increases in local blood flow, establishing CBW amplitude as a potential biomarker of subcortical hemodynamics, and a potential therapeutic modality.</div></div>\",\"PeriodicalId\":9206,\"journal\":{\"name\":\"Brain Stimulation\",\"volume\":\"18 6\",\"pages\":\"Pages 1810-1820\"},\"PeriodicalIF\":8.4000,\"publicationDate\":\"2025-09-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain Stimulation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1935861X25003419\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain Stimulation","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1935861X25003419","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
The effects of intracranial stimulation on local neurovascular responses in humans
Background
Deep brain stimulation (DBS) is used to treat neurological and psychiatric disorders by modulating neuronal circuits. However, the effects of electrical stimulation on the neurovascular unit remain poorly understood due to limitations of capturing microvascular changes near implanted leads. This motivated us to investigate the cardioballistic waveform (CBW) as an electrophysiological surrogate of vascular dynamics in response to microstimulation.
Methods
Microelectrode recordings (n = 193; 108 patients) were obtained during DBS implantation surgery from two electrodes (∼600 μm apart) before and after microstimulation through one electrode. Generalized linear mixed models assessed CBW amplitude changes following 1 Hz or 100 Hz stimulation across basal ganglia regions and white matter. Neuronal activity was also analyzed, including phase-locking to the cardiac cycle, firing rates and patterns, and micro-LFP features. An analytical model interpreted CBW amplitudes as pressure-driven vessel wall expansion, enabling estimation of stimulation-evoked vasodilation and cerebral blood flow.
Results
CBW amplitudes increased significantly after 100 Hz stimulation at the stimulating electrode, but not at the non-stimulating electrode or after 1 Hz stimulation. Significant region-specific effects were observed in the ventral intermediate nucleus (Vim; 107 ± 13 %), subthalamic nucleus (STN; 79 ± 7 %), and globus pallidus internus (GPi; 78 ± 8 %), but not in white matter (WM; 50 ± 14 %) or substantia nigra pars reticulata (SNr; 45 ± 8 %). Across 50 recorded single units, 18 (36 %) were phase-locked to the cardiac cycle, but stimulation did not alter phase-locking value, and changes in spiking or micro-LFP features before versus after stimulation did not scale with CBW changes. Modelling showed that the mean 88 % CBW increase across Vim, STN, and GPi corresponds to an acute increase in cerebral blood flow.
Conclusion
CBW recordings reveal that high-frequency DBS evokes region-specific vascular responses which can be modeled as substantial increases in local blood flow, establishing CBW amplitude as a potential biomarker of subcortical hemodynamics, and a potential therapeutic modality.
期刊介绍:
Brain Stimulation publishes on the entire field of brain stimulation, including noninvasive and invasive techniques and technologies that alter brain function through the use of electrical, magnetic, radiowave, or focally targeted pharmacologic stimulation.
Brain Stimulation aims to be the premier journal for publication of original research in the field of neuromodulation. The journal includes: a) Original articles; b) Short Communications; c) Invited and original reviews; d) Technology and methodological perspectives (reviews of new devices, description of new methods, etc.); and e) Letters to the Editor. Special issues of the journal will be considered based on scientific merit.