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Modern Approaches to Augmentation of Brain Function pp 463–483Cite as

Deep Brain Stimulation for Parkinson’s Disease: Clinical Efficacy and Future Directions for Enhancing Motor Function

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Part of the book series: Contemporary Clinical Neuroscience ((CCNE))

Abstract

Deep Brain Stimulation (DBS) is a well-established procedure that produces a significant improvement in motor symptoms in patients with advanced Parkinson’s disease (PD). While the motor function improvement has been documented extensively, the effects of DBS on non-motor symptoms, such as sleep, cognition, and mood, have been less studied. This review will summarize the extensive clinical evidence on the effects of DBS in PD, and emerging evidence on non-motor symptoms as well as the advances in technology that allows a more precise lead placement and better outcomes. Future directions in the field of neuromodulation and strategies to improve overall brain function will be reviewed. The recent advances in technology provide the ability to deliver stimulation adaptively based on cortical and subcortical brain signals, and subsequently a more physiological and precise modulation of the impaired motor network.

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References

  • Benabid AL, Cinquin P, Lavalle S, Le Bas JF, Demongeot J, de Rougemont J (1987) Computer-driven robot for stereotactic surgery connected to CT scan and magnetic resonance imaging. Technological design and preliminary results. Appl Neurophysiol 50(1–6):153–154

    CAS  PubMed  Google Scholar 

  • Blumenfeld Z, Bronte-Stewart H (2015) High frequency deep brain stimulation and neural rhythms in Parkinson’s disease. Neuropsychol Rev 25(4):384–397

    Article  PubMed  Google Scholar 

  • Bos MJ, Alzate Sanchez AM, Smeets AYJM, Bancone R, Ackermans L, Absalom AR et al (2019) Effect of anesthesia on microelectrode recordings during deep brain stimulation surgery in tourette syndrome patients. Stereotact Funct Neurosurg 97(4):225–231

    Article  PubMed  Google Scholar 

  • Boutet A, Hancu I, Saha U, Crawley A, Xu DS, Ranjan M et al (2019) 3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences. J Neurosurg 132(2):586–594

    Article  PubMed  Google Scholar 

  • Cagnan H, Brown P, Bourget D, Denison T (2015) Inertial-based control system concepts for the treatment of movement disorders. Int Solid State Sens Actuators Microsyst Conf 18:70–73

    PubMed  PubMed Central  Google Scholar 

  • Cagnan H, Pedrosa D, Little S, Pogosyan A, Cheeran B, Aziz T et al (2016) Stimulating at the right time: phase-specific deep brain stimulation. Brain J Neurol 140(Pt 1):132–145

    Google Scholar 

  • Cagnan H, Denison T, McIntyre C, Brown P (2019) Emerging technologies for improved deep brain stimulation. Nat Biotechnol 37(9):1024–1033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Candela S, Vanegas MI, Darling A, Ortigoza-Escobar JD, Alamar M, Muchart J et al (2018) Frameless robot-assisted pallidal deep brain stimulation surgery in pediatric patients with movement disorders: precision and short-term clinical results. J Neurosurg Pediatr 22(4):416–425

    Article  PubMed  Google Scholar 

  • Cernera S, Okun MS, Gunduz A (2019) A review of cognitive outcomes across movement disorder patients undergoing deep brain stimulation. Front Neurol 10:419

    Article  PubMed  PubMed Central  Google Scholar 

  • Coenen VA, Varkuti B, Parpaley Y, Skodda S, Prokop T, Urbach H et al (2017) Postoperative neuroimaging analysis of DRT deep brain stimulation revision surgery for complicated essential tremor. Acta Neurochir 159(5):779–787

    Article  PubMed  Google Scholar 

  • Combs HL, Folley BS, Berry DT, Segerstrom SC, Han DY, Anderson-Mooney AJ et al (2015) Cognition and depression following deep brain stimulation of the subthalamic nucleus and globus pallidus pars internus in Parkinson’s disease: a meta-analysis. Neuropsychol Rev 25(4):439–454

    Article  PubMed  Google Scholar 

  • Cordeiro JG, Diaz A, Davis JK, Di Luca DG, Farooq G, Luca CC et al (2020) Safety of noncontrast imaging–guided deep brain stimulation electrode placement in Parkinson disease. World Neurosurg 134:e1008–e1e14

    Article  PubMed  Google Scholar 

  • de Hemptinne C, Ryapolova-Webb ES, Air EL, Garcia PA, Miller KJ, Ojemann JG et al (2013) Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. Proc Natl Acad Sci U S A 110(12):4780–4785

    Article  PubMed  PubMed Central  Google Scholar 

  • de Schlichting E, Coll G, Zaldivar-Jolissaint JF, Coste J, Marques AR, Mulliez A et al (2019) Pulse generator battery life in deep brain stimulation: out with the old… in with the less durable? Acta Neurochir 161(10):2043–2046

    Article  PubMed  Google Scholar 

  • Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K et al (2006) A randomized trial of deep-brain stimulation for Parkinson’s disease. N Engl J Med 355(9):896–908

    Article  CAS  PubMed  Google Scholar 

  • Eusebio A, Thevathasan W, Gaynor LD, Pogosyan A, Bye E, Foltynie T et al (2010) Deep brain stimulation can suppress pathological synchronisation in parkinsonian patients. J Neurol Neurosurg Psychiatry 82(5):569–573

    Article  PubMed  Google Scholar 

  • Faraji AH, Kokkinos V, Sweat JC, Crammond DJ, Richardson RM. Robotic-Assisted Stereotaxy for Deep Brain Stimulation Lead Implantation in Awake Patients. Oper Neurosurg (Hagerstown). 2020 Sep 15;19(4):444-452. https://doi.org/10.1093/ons/opaa029. PMID: 32147722

  • França C, Barbosa ER, Iglesio R, Teixeira MJ, Cury RG (2019) Interleaving stimulation in Parkinson disease: interesting to whom? World Neurosurg 130:e786–e793

    Article  PubMed  Google Scholar 

  • Hell F, Palleis C, Mehrkens JH, Koeglsperger T, Bötzel K (2019) Deep brain stimulation programming 2.0: future perspectives for target identification and adaptive closed loop stimulation. Front Neurol 10:314

    Article  PubMed  PubMed Central  Google Scholar 

  • Herron JA, Thompson MC, Brown T, Chizeck HJ, Ojemann JG, Ko AL (2017) Chronic electrocorticography for sensing movement intention and closed-loop deep brain stimulation with wearable sensors in an essential tremor patient. J Neurosurg 127(3):580–587

    Article  PubMed  Google Scholar 

  • Herz DM, Little S, Pedrosa DJ, Tinkhauser G, Cheeran B, Foltynie T et al (2018) Mechanisms underlying decision-making as revealed by deep-brain stimulation in patients with Parkinson’s disease. Curr Biol 28(8):1169–78.e6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ho AL, Ali R, Connolly ID, Henderson JM, Dhall R, Stein SC et al (2018) Awake versus asleep deep brain stimulation for Parkinson’s disease: a critical comparison and meta-analysis. J Neurol Neurosurg Psychiatry 89:687–691

    Article  PubMed  Google Scholar 

  • Howell B, McIntyre CC (2017) Role of soft-tissue heterogeneity in computational models of deep brain stimulation. Brain Stimul 10(1):46–50

    Article  PubMed  Google Scholar 

  • Israeli-Korn SD, Fay-Karmon T, Tessler S, Yahalom G, Benizri S, Strauss H et al (2019) Decreasing battery life in subthalamic deep brain stimulation for Parkinson’s disease with repeated replacements: just a matter of energy delivered? Brain Stimul 12(4):845–850

    Article  PubMed  Google Scholar 

  • Kirsch AD, Hassin-Baer S, Matthies C, Volkmann J, Steigerwald F (2018) Anodic versus cathodic neurostimulation of the subthalamic nucleus: a randomized-controlled study of acute clinical effects. Parkinsonism Relat Disord 55:61–67

    Article  PubMed  Google Scholar 

  • Kuhn AA, Williams D, Kupsch A, Limousin P, Hariz M, Schneider GH et al (2004) Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance. Brain 127(Pt 4):735–746

    Article  PubMed  Google Scholar 

  • Kühn AA, Kupsch A, Schneider G-H, Brown P (2006) Reduction in subthalamic 8-35 Hz oscillatory activity correlates with clinical improvement in Parkinson’s disease. Eur J Neurosci 23(7):1956–1960

    Article  PubMed  Google Scholar 

  • Little S, Brown P (2012) What brain signals are suitable for feedback control of deep brain stimulation in Parkinson’s disease? Ann N Y Acad Sci 1265(1):9–24

    Article  PubMed  PubMed Central  Google Scholar 

  • Little S, Pogosyan A, Neal S, Zavala B, Zrinzo L, Hariz M et al (2013) Adaptive deep brain stimulation in advanced Parkinson disease. Ann Neurol 74(3):449–457

    Article  PubMed  PubMed Central  Google Scholar 

  • Little S, Beudel M, Zrinzo L, Foltynie T, Limousin P, Hariz M et al (2016a) Bilateral adaptive deep brain stimulation is effective in Parkinson’s disease. J Neurol Neurosurg Psychiatry 87(7):717

    Article  PubMed  Google Scholar 

  • Little S, Tripoliti E, Beudel M, Pogosyan A, Cagnan H, Herz D et al (2016b) Adaptive deep brain stimulation for Parkinson’s disease demonstrates reduced speech side effects compared to conventional stimulation in the acute setting. J Neurol Neurosurg Psychiatry 87(12):1388–1389

    Article  PubMed  Google Scholar 

  • Liu Z, He S, Li L (2019) General anesthesia versus local anesthesia for deep brain stimulation in Parkinson’s disease: a meta-analysis. Stereotact Funct Neurosurg 97(5–6):381–390

    Article  PubMed  Google Scholar 

  • McIntyre CC, Savasta M, Walter BL, Vitek JL (2004) How does deep brain stimulation work? Present understanding and future questions. J Clin Neurophysiol 21(1):40–50

    Article  PubMed  Google Scholar 

  • Merola A, Romagnolo A, Krishna V, Pallavaram S, Carcieri S, Goetz S et al (2020) Current directions in deep brain stimulation for Parkinson’s disease—directing current to maximize clinical benefit. Neurol Ther 9(1):25–41

    Article  PubMed  PubMed Central  Google Scholar 

  • Morishita T, Higuchi M-A, Kobayashi H, Abe H, Higashi T, Inoue T (2019) A retrospective evaluation of thalamic targeting for tremor deep brain stimulation using high-resolution anatomical imaging with supplementary fiber tractography. J Neurol Sci 398:148–156

    Article  PubMed  Google Scholar 

  • Neudorfer C, Hunsche S, Hellmich M, El Majdoub F, Maarouf M (2018) Comparative study of robot-assisted versus conventional frame-based deep brain stimulation stereotactic neurosurgery. Stereotact Funct Neurosurg 96(5):327–334

    Article  PubMed  Google Scholar 

  • Odekerken VJ, van Laar T, Staal MJ, Mosch A, Hoffmann CF, Nijssen PC et al (2013) Subthalamic nucleus versus globus pallidus bilateral deep brain stimulation for advanced Parkinson’s disease (NSTAPS study): a randomised controlled trial. Lancet Neurol 12(1):37–44

    Article  PubMed  Google Scholar 

  • Okun MS, Gallo BV, Mandybur G, Jagid J, Foote KD, Revilla FJ et al (2012) Subthalamic deep brain stimulation with a constant-current device in Parkinson’s disease: an open-label randomised controlled trial. Lancet Neurol 11(2):140–149

    Article  PubMed  Google Scholar 

  • Ramirez-Zamora A, Ostrem JL (2018) Globus pallidus interna or subthalamic nucleus deep brain stimulation for Parkinson disease: a review. JAMA Neurol 75(3):367–372

    Article  PubMed  Google Scholar 

  • Ranjan M, Boutet A, Xu DS, Lozano CS, Kumar R, Fasano A et al (2018) Subthalamic nucleus visualization on routine clinical preoperative MRI scans: a retrospective study of clinical and image characteristics predicting its visualization. Stereotact Funct Neurosurg 96(2):120–126

    Article  PubMed  Google Scholar 

  • Reck C, Florin E, Wojtecki L, Krause H, Groiss S, Voges J et al (2009) Characterisation of tremor-associated local field potentials in the subthalamic nucleus in Parkinson’s disease. Eur J Neurosci 29(3):599–612

    Article  PubMed  Google Scholar 

  • Reich MM, Steigerwald F, Sawalhe AD, Reese R, Gunalan K, Johannes S et al (2015) Short pulse width widens the therapeutic window of subthalamic neurostimulation. Ann Clin Transl Neurol 2(4):427–432

    Article  PubMed  PubMed Central  Google Scholar 

  • Rosa M, Arlotti M, Ardolino G, Cogiamanian F, Marceglia S, Di Fonzo A et al (2015) Adaptive deep brain stimulation in a freely moving Parkinsonian patient. Mov Disord 30(7):1003–1005

    Article  PubMed  PubMed Central  Google Scholar 

  • Russo M, Cousins MJ, Brooker C, Taylor N, Boesel T, Sullivan R et al (2018) Effective relief of pain and associated symptoms with closed-loop spinal cord stimulation system: preliminary results of the avalon study. Neuromodulation 21(1):38–47

    Article  PubMed  Google Scholar 

  • Schade CM, Schultz DM, Tamayo N, Iyer S, Panken E (2011) Automatic adaptation of neurostimulation therapy in response to changes in patient position: results of the Posture Responsive Spinal Cord Stimulation (PRS) Research Study. Pain Physician 14(5):407–417

    Article  PubMed  Google Scholar 

  • Schlenstedt C, Shalash A, Muthuraman M, Falk D, Witt K, Deuschl G (2017) Effect of high-frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson’s disease: a systematic review and meta-analysis. Eur J Neurol 24(1):18–26

    Article  CAS  PubMed  Google Scholar 

  • Schnitzler AS, Mir PM, Brodsky MB, Verhagen LV, Groppa SG, Cheeran BC, Karst EK, Defresne FD, Vesper JV (2019) Directional versus omnidirectional deep brain stimulation for Parkinson’s disease: results of a prospective, blinded, multi-center, single-arm crossover study [abstract]. Mov Disord 34(Suppl 2)

    Google Scholar 

  • Schuepbach WM, Rau J, Knudsen K, Volkmann J, Krack P, Timmermann L et al (2013) Neurostimulation for Parkinson’s disease with early motor complications. N Engl J Med 368(7):610–622

    Article  CAS  PubMed  Google Scholar 

  • Schultz DM, Webster L, Kosek P, Dar U, Tan Y, Sun M (2012) Sensor-driven position-adaptive spinal cord stimulation for chronic pain. Pain Physician 15(1):1–12

    Article  PubMed  Google Scholar 

  • Schüpbach WMM, Chabardes S, Matthies C, Pollo C, Steigerwald F, Timmermann L et al (2017) Directional leads for deep brain stimulation: opportunities and challenges. Mov Disord 32(10):1371–1375

    Article  PubMed  Google Scholar 

  • Soh D, Lozano AM, Fasano A (2019) Hybrid deep brain stimulation system to manage stimulation-induced side effects in essential tremor patients. Parkinsonism Relat Disord 58:85–86

    Article  PubMed  Google Scholar 

  • Steigerwald F, Muller L, Johannes S, Matthies C, Volkmann J (2016) Directional deep brain stimulation of the subthalamic nucleus: a pilot study using a novel neurostimulation device. Mov Disord 31(8):1240–1243

    Article  PubMed  PubMed Central  Google Scholar 

  • Steigerwald F, Timmermann L, Kühn A, Schnitzler A, Reich MM, Kirsch AD et al (2018) Pulse duration settings in subthalamic stimulation for Parkinson’s disease. Mov Disord 33(1):165–169

    Article  PubMed  Google Scholar 

  • Sudhyadhom A, Haq IU, Foote KD, Okun MS, Bova FJ (2009) A high resolution and high contrast MRI for differentiation of subcortical structures for DBS targeting: the Fast Gray Matter Acquisition T1 Inversion Recovery (FGATIR). Neuroimage 47(Suppl 2):T44–T52

    Article  PubMed  Google Scholar 

  • Sun FT, Morrell MJ (2014) Closed-loop neurostimulation: the clinical experience. Neurotherapeutics 11(3):553–563

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swann NC, de Hemptinne C, Miocinovic S, Qasim S, Wang SS, Ziman N et al (2016) Gamma oscillations in the hyperkinetic state detected with chronic human brain recordings in Parkinson’s disease. J Neurosci 36(24):6445–6458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swann NC, Hemptinne C, Thompson MC, Miocinovic S, Miller AM, Gilron R et al (2018) Adaptive deep brain stimulation for Parkinson’s disease using motor cortex sensing. J Neural Eng 15(4):046006

    Article  PubMed  PubMed Central  Google Scholar 

  • Tepper Á, Henrich MC, Schiaffino L, Rosado Muñoz A, Gutiérrez A, Guerrero MJ (2017) Selection of the optimal algorithm for real-time estimation of beta band power during DBS surgeries in patients with Parkinson’s disease. Comput Intell Neurosci 2017:1512504

    Article  PubMed  PubMed Central  Google Scholar 

  • Thevathasan W, Moro E (2019) What is the therapeutic mechanism of pedunculopontine nucleus stimulation in Parkinson’s disease? Neurobiol Dis 128:67–74

    Article  PubMed  Google Scholar 

  • Thompson JA, Yin D, Ojemann SG, Abosch A (2017) Use of the putamen as a surrogate anatomical marker for the internal segment of the globus pallidus in deep brain stimulation surgery. Stereotact Funct Neurosurg 95(4):229–235

    Article  PubMed  Google Scholar 

  • Tsai S-T, Chen T-Y, Lin S-H, Chen S-Y (2019) Five-year clinical outcomes of local versus general anesthesia deep brain stimulation for Parkinson’s disease. Parkinsons Dis 2019:5676345

    PubMed  PubMed Central  Google Scholar 

  • Valldeoriola F, Munoz E, Rumia J, Roldan P, Camara A, Compta Y et al (2019) Simultaneous low-frequency deep brain stimulation of the substantia nigra pars reticulata and high-frequency stimulation of the subthalamic nucleus to treat levodopa unresponsive freezing of gait in Parkinson’s disease: a pilot study. Parkinsonism Relat Disord 60:153–157

    Article  PubMed  Google Scholar 

  • Vassal F, Dilly D, Boutet C, Bertholon F, Charier D, Pommier B (2020) White matter tracts involved by deep brain stimulation of the subthalamic nucleus in Parkinson’s disease: a connectivity study based on preoperative diffusion tensor imaging tractography. Br J Neurosurg 34(2):187–195

    Article  PubMed  Google Scholar 

  • Venkatraghavan L, Rakhman E, Krishna V, Sammartino F, Manninen P, Hutchison W (2016) The effect of general anesthesia on the microelectrode recordings from pallidal neurons in patients with dystonia. J Neurosurg Anesthesiol 28(3):256–261

    Article  PubMed  Google Scholar 

  • Vitek J, Jain R, Starr P (2019) Two year outcomes: a prospective, double blinded, multicenter randomized controlled trial evaluating deep brain stimulation with a new multiple source, constant current rechargeable system in Parkinson’s disease (INTREPID) (P1.8-026). Neurology 92(15 Suppl):P1.8-026

    Google Scholar 

  • Vitek J, Jain R, Starr P (2020) Three-year follow-up of a prospective, double-blinded, multi-center randomized controlled trial evaluating deep brain stimulation with multiple source, constant-current rechargeable system for treatment of Parkinson’s disease (INTREPID) (1365). Neurology 94(15 Suppl):1365

    Google Scholar 

  • Wang J, Nebeck S, Muralidharan A, Johnson MD, Vitek JL, Baker KB (2016) Coordinated reset deep brain stimulation of subthalamic nucleus produces long-lasting, dose-dependent motor improvements in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine non-human primate model of parkinsonism. Brain Stimul 9(4):609–617

    Article  PubMed  Google Scholar 

  • Wang JW, Zhang YQ, Zhang XH, Wang YP, Li JP, Li YJ (2017) Deep brain stimulation of pedunculopontine nucleus for postural instability and gait disorder after Parkinson disease: a meta-analysis of individual patient data. World Neurosurg 102:72–78

    Article  PubMed  Google Scholar 

  • Weaver FM, Follett K, Stern M, Hur K, Harris C, Marks WJ Jr et al (2009) Bilateral deep brain stimulation vs best medical therapy for patients with advanced Parkinson disease: a randomized controlled trial. JAMA 301(1):63–73

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams A, Gill S, Varma T, Jenkinson C, Quinn N, Mitchell R et al (2010) Deep brain stimulation plus best medical therapy versus best medical therapy alone for advanced Parkinson’s disease (PD SURG trial): a randomised, open-label trial. Lancet Neurol 9(6):581–591

    Article  PubMed  PubMed Central  Google Scholar 

  • Yasin H, Hoff H-J, Blümcke I, Simon M (2019) Experience with 102 frameless stereotactic biopsies using the neuromate robotic device. World Neurosurg 123:e450–e456

    Article  PubMed  Google Scholar 

  • Zuzuarregui JRP, Ostrem JL (2020) The impact of deep brain stimulation on sleep in Parkinson’s disease: an update. J Parkinsons Dis 10(2):393–404

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA

    Corneliu C. Luca

  2. Department of Neurosurgery, University of Miami Miller School of Medicine, Miami, FL, USA

    Joacir Graciolli Cordeiro, Iahn Cajigas & Jonathan Jagid

Authors
  1. Corneliu C. Luca
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  2. Joacir Graciolli Cordeiro
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  3. Iahn Cajigas
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  4. Jonathan Jagid
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Corresponding author

Correspondence to Corneliu C. Luca .

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Editors and Affiliations

  1. Department of Neurosurgery, University of Miami, Miami, FL, USA

    Ioan Opris

  2. Center for Bioelectrical Interfaces, National Research University Higher School of Economics, Moscow, Russia

    Mikhail A. Lebedev

  3. Greenville Health System, University of South Carolina, Greenville, SC, USA

    Manuel F. Casanova

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Luca, C.C., Cordeiro, J.G., Cajigas, I., Jagid, J. (2021). Deep Brain Stimulation for Parkinson’s Disease: Clinical Efficacy and Future Directions for Enhancing Motor Function. In: Opris, I., A. Lebedev, M., F. Casanova, M. (eds) Modern Approaches to Augmentation of Brain Function. Contemporary Clinical Neuroscience. Springer, Cham. https://doi.org/10.1007/978-3-030-54564-2_22

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