Precision targeting in the globus pallidus interna: insights from the multicenter, prospective, blinded VA/NINDS CSP 468 study

Shawn D’Souza School of Medicine, Virginia Commonwealth University, Richmond, Virginia;

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Vikram Seshadri School of Medicine, Virginia Commonwealth University, Richmond, Virginia;

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Jamie Toms Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana;

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Pierre D’Haese Department of Neuroradiology, West Virginia University Rockefeller Neuroscience Institute, Morgantown, West Virginia;

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Benoit M. Dawant Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, Tennessee;

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Rui Li Department of Electrical and Computer Engineering, Vanderbilt University, Nashville, Tennessee;

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Harsh P. Shah Department of Neurosurgery, Virginia Commonwealth University Health, Richmond, Virginia;

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Paul Koch Department of Neurosurgery, Virginia Commonwealth University Health, Richmond, Virginia;
Department of Neurosurgery, Richmond VA Medical Center, Richmond, Virginia;

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Paul Larson Department of Neurosurgery, Southern Arizona VA Health Care System, Tucson, Arizona; and
Department of Neurosurgery, University of Arizona, Tucson, Arizona

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Kathryn L. Holloway Department of Neurosurgery, Virginia Commonwealth University Health, Richmond, Virginia;
Department of Neurosurgery, Richmond VA Medical Center, Richmond, Virginia;

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OBJECTIVE

Deep brain stimulation (DBS) targeting the globus pallidus interna (GPi) has been shown to significantly improve motor symptoms for the treatment of medication-refractory Parkinson’s disease. Yet, heterogeneity in clinical outcomes persists, possibly due to suboptimal target identification within the GPi. By leveraging robust sampling of the GPi and 6-month postsurgical outcomes, this study aims to determine optimal symptom-specific GPi DBS targets.

METHODS

In this study, the authors analyzed the anatomical lead location and 6-month postsurgical, double-blinded outcome measures of 86 patients who underwent bilateral GPi DBS. These patients were selected from the multicenter Veterans Affairs (VA)/National Institutes of Neurological Disorders and Stroke (NINDS) Cooperative Studies Program (CSP) 468 study to identify the optimal target zones ("sweet spots") for the control of overall motor (United Parkinson’s Disease Rating Scale [UPDRS]–III), axial, tremor, rigidity, and bradykinesia symptoms. Lead coordinates were normalized to Montreal Neurological Institute space and the optimal target zones were identified and validated using a leave-one-patient-out approach.

RESULTS

The authors’ findings revealed statistically significant optimal target zones for UPDRS-III (R = 0.37, p < 0.001), axial (R = 0.22, p = 0.042), rigidity (R = 0.20, p = 0.021), and bradykinesia (R = 0.23, p = 0.004) symptoms. These zones were localized within the primary motor and premotor subdivisions of the GPi. Interestingly, these zones extended beyond the GPi lateral border into the GPi–globus pallidus externa (GPe) lamina and into the GPe, but they did not reach the GPi ventral border, challenging traditional surgical approaches based on pallidotomies.

CONCLUSIONS

Drawing upon a robust dataset, this research effectively delineates specific optimal target zones for not only overall motor improvement but also symptom subscores. These insights hold the potential to enhance the precision of targeting in subsequent bilateral GPi DBS surgical procedures.

ABBREVIATIONS

AC-PC = anterior commissure–posterior commissure; CRAVE = CRAnial Vault Explorer; CSP = Cooperative Studies Program; DBS = deep brain stimulation; GPe = globus pallidus externa; GPi = globus pallidus interna; LOOCV = leave-one-patient-out cross-validation; MNI = Montreal Neurological Institute; PD = Parkinson’s disease; STN = subthalamic nucleus; UPDRS = United Parkinson’s Disease Rating Scale; VA = Veterans Affairs; VTA = volume of tissue activated.

Supplementary Materials

    • Supplemental Figs. 1 and 2 (PDF 1,899 KB)
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  • 1

    Anderson VC, Burchiel KJ, Hogarth P, Favre J, Hammerstad JP. Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson disease. Arch Neurol. 2005;62(4):554560.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Follett KA, Weaver FM, Stern M, et al. Pallidal versus subthalamic deep-brain stimulation for Parkinson’s disease. N Engl J Med. 2010;362(22):20772091.

  • 3

    Odekerken VJJ, van Laar T, Staal MJ, et al. Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson’s disease (NSTAPS study): a randomised controlled trial. Lancet Neurol. 2013;12(1):3744.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Okun MS, Fernandez HH, Wu SS, et al. Cognition and mood in Parkinson’s disease in subthalamic nucleus versus globus pallidus interna deep brain stimulation: the COMPARE trial. Ann Neurol. 2009;65(5):586595.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Accolla EA, Pollo C. Mood effects after deep brain stimulation for Parkinson’s disease: an update. Front Neurol. 2019;10:617.

  • 6

    Au KLK, Wong JK, Tsuboi T, et al. Globus pallidus internus (GPi) deep brain stimulation for Parkinson’s disease: expert review and commentary. Neurol Ther. 2021;10(1):730.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Richardson RM, Ostrem JL, Starr PA. Surgical repositioning of misplaced subthalamic electrodes in Parkinson’s disease: location of effective and ineffective leads. Stereotact Funct Neurosurg. 2009;87(5):297303.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Sobesky L, Goede L, Odekerken VJJ, et al. Subthalamic and pallidal deep brain stimulation: are we modulating the same network?. Brain. 2022;145(1):251262.

  • 9

    Weaver FM, Follett KA, Stern M, et al. Randomized trial of deep brain stimulation for Parkinson disease: thirty-six-month outcomes. Neurology. 2012;79(1):5565.

  • 10

    D’Haese PF, Pallavaram S, Li R, et al. CranialVault and its CRAVE tools: a clinical computer assistance system for deep brain stimulation (DBS) therapy. Med Image Anal. 2012;16(3):744753.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Horn A, Reich M, Vorwerk J, et al. Connectivity predicts deep brain stimulation outcome in Parkinson disease. Ann Neurol. 2017;82(1):6778.

  • 12

    McIntyre CC, Grill WM, Sherman DL, Thakor NV. Cellular effects of deep brain stimulation: model-based analysis of activation and inhibition. J Neurophysiol. 2004;91(4):14571469.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Åström M, Diczfalusy E, Martens H, Wardell K. Relationship between neural activation and electric field distribution during deep brain stimulation. IEEE Trans Biomed Eng. 2015;62(2):664672.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Hemm S, Mennessier G, Vayssiere N, Cif L, El Fertit H, Coubes P. Deep brain stimulation in movement disorders: stereotactic coregistration of two-dimensional electrical field modeling and magnetic resonance imaging. J Neurosurg. 2005;103(6):949955.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Vasques X, Cif L, Hess O, Gavarini S, Mennessier G, Coubes P. Stereotactic model of the electrical distribution within the internal globus pallidus during deep brain stimulation. J Comput Neurosci. 2009;26(1):109118.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Dembek TA, Baldermann JC, Petry-Schmelzer JN, et al. Sweetspot mapping in deep brain stimulation: strengths and limitations of current approaches. Neuromodulation. 2022;25(6):877887.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Neudorfer C, Butenko K, Oxenford S, et al. Lead-DBS v3.0: mapping deep brain stimulation effects to local anatomy and global networks. Neuroimage. 2023;268:119862.

  • 18

    van Albada SJ, Robinson PA. Transformation of arbitrary distributions to the normal distribution with application to EEG test-retest reliability. J Neurosci Methods. 2007;161(2):205211.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Reich MM, Horn A, Lange F, et al. Probabilistic mapping of the antidystonic effect of pallidal neurostimulation: a multicentre imaging study. Brain. 2019;142(5):13861398.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Ríos AS, Oxenford S, Neudorfer C, et al. Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer’s disease. Nat Commun. 2022;13(1):7707.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Ewert S, Plettig P, Li N, et al. Toward defining deep brain stimulation targets in MNI space: a subcortical atlas based on multimodal MRI, histology and structural connectivity. Neuroimage. 2018;170:271282.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Yushkevich PA, Piven J, Hazlett HC, et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage. 2006;31(3):11161128.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Fonov VS, Evans AC, McKinstry RC, Almli CR, Collins DL. Unbiased nonlinear average age-appropriate brain templates from birth to adulthood. Neuroimage. 2009;47(Suppl 1):S102.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Fonov V, Evans AC, Botteron K, Almli CR, McKinstry RC, Collins DL. Unbiased average age-appropriate atlases for pediatric studies. Neuroimage. 2011;54(1):313327.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Barow E, Neumann WJ, Brücke C, et al. Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements. Brain. 2014;137(Pt 11):30123024.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Holland MT, Jiao J, Mantovani A, et al. Identifying the therapeutic zone in globus pallidus deep brain stimulation for Parkinson’s disease. J Neurosurg. 2022;138(2):329336.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Vayssiere N, van der Gaag N, Cif L, et al. Deep brain stimulation for dystonia confirming a somatotopic organization in the globus pallidus internus. J Neurosurg. 2004;101(2):181188.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Vidailhet M, Yelnik J, Lagrange C, et al. Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study. Lancet Neurol. 2009;8(8):709717.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Guo T, Finnis KW, Parrent AG, Peters TM. Development and application of functional databases for planning deep-brain neurosurgical procedures. Med Image Comput Comput-Assist Interv. 2005;8(Pt 1):835842.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Finnis KW, Starreveld YP, Parrent AG, Sadikot AF, Peters TM. Application of a population based electrophysiological database to the planning and guidance of deep brain stereotactic neurosurgery. In: Dohi T, Kikinis R, eds. Medical Image Computing and Computer-Assisted Intervention – MICCAI 2002. Springer; 2002. Accessed April 24, 2024. https://doi.org/10.1007/3-540-45787-9_9

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    D’Haese PF, Cetinkaya E, Kao C, Fitzpatrick JM, Konrad PE, Dawant BM. Toward the creation of an electrophysiological atlas for the pre-operative planning and intra-operative guidance of deep brain stimulators (DBS) implantation. In: Barillot C, Haynor DR, Hellier P, eds. Medical Image Computing and Computer-Assisted Intervention – MICCAI 2004. Springer; 2004. Accessed April 24, 2024. https://doi.org/10.1007/978-3-540-30135-6_89

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Horn A, Li N, Dembek TA, et al. Lead-DBS v2: towards a comprehensive pipeline for deep brain stimulation imaging. Neuroimage. 2019;184:293316.

  • 33

    Bertino S, Basile GA, Bramanti A, et al. Spatially coherent and topographically organized pathways of the human globus pallidus. Hum Brain Mapp. 2020;41(16):46414661.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Laitinen LV, Bergenheim AT, Hariz MI. Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms. Stereotact Funct Neurosurg. 1992;58(1-4):1421.

  • 35

    Lozano A, Hutchison W, Kiss Z, Tasker R, Davis K, Dostrovsky J. Methods for microelectrode-guided posteroventral pallidotomy. J Neurosurg. 1996;84(2):194202.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Starr PA. Placement of deep brain stimulators into the subthalamic nucleus or globus pallidus internus: technical approach. Stereotact Funct Neurosurg. 2002;79(3-4):118145.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37

    Gross RE, Lombardi WJ, Lang AE, et al. Relationship of lesion location to clinical outcome following microelectrode-guided pallidotomy for Parkinson’s disease. Brain. 1999;122(Pt 3):405416.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38

    Vitek JL, Bakay RAE, Hashimoto T, et al. Microelectrode-guided pallidotomy: technical approach and its application in medically intractable Parkinson’s disease. J Neurosurg. 1998;88(6):10271043.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39

    Paulo DL, Johnson GW, Doss DJ, et al. Intraoperative physiology augments atlas-based data in awake deep brain stimulation. J Neurol Neurosurg Psychiatry. 2023;95(1):8696.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Phibbs FT, Pallavaram S, Tolleson C, D’Haese PF, Dawant BM. Use of efficacy probability maps for the post-operative programming of deep brain stimulation in essential tremor. Parkinsonism Relat Disord. 2014;20(12):13411344.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Lai Y, He N, Wei H, et al. Value of functional connectivity in outcome prediction for pallidal stimulation in Parkinson disease. J Neurosurg. 2022;138(1):2737.

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