Increased anteroventral striatal dopamine transporter and motor recovery after subthalamic deep brain stimulation in Parkinson’s disease

Takao Nozaki MD, PhD1, Kenji Sugiyama MD, PhD2, Tetsuya Asakawa MD, PhD3, Hiroki Namba MD, PhD4, Masamichi Yokokura MD, PhD5, Tatsuhiro Terada MD, PhD6,9, Tomoyasu Bunai PhD7,9, and Yasuomi Ouchi MD, PhD8,9
View More View Less
  • 1 Department of Neurosurgery, Hamamatsu University School of Medicine, Hamamatsu, Japan;
  • | 2 Department of Neurosurgery, Toyoda Eisei Hospital, Iwata, Japan;
  • | 3 Department of Neurology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China;
  • | 4 Department of Neurosurgery, JA Shizuoka Kohseiren Enshu Hospital, Hamamatsu, Japan;
  • | 5 Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan;
  • | 6 Department of Neurology, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan;
  • | 7 Department of Neurology, Hamamatsu University School of Medicine, Hamamatsu, Japan;
  • | 8 Hamamatsu PET Imaging Center, Hamamatsu Medical Photonics Foundation, Hamamatsu, Japan; and
  • | 9 Department of Biofunctional Imaging, Preeminent Medical Photonics Education & Research Center, Hamamatsu University School of Medicine, Hamamatsu, Japan
Restricted access

Purchase Now

USD  $45.00

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
USD  $45.00
USD  $515.00
USD  $612.00
Print or Print + Online Sign in

OBJECTIVE

Subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease is effective; however, its mechanism is unclear. To investigate the degree of neuronal terminal survival after STN-DBS, the authors examined the striatal dopamine transporter levels before and after treatment in association with clinical improvement using PET with [11C]2β-carbomethoxy-3β-(4-fluorophenyl)tropane ([11C]CFT).

METHODS

Ten patients with Parkinson’s disease who had undergone bilateral STN-DBS were scanned twice with [11C]CFT PET just before and 1 year after surgery. Correlation analysis was conducted between [11C]CFT binding and off-period Unified Parkinson’s Disease Rating Scale (UPDRS) scores assessed preoperatively and postoperatively.

RESULTS

[11C]CFT uptake reduced significantly in the posterodorsal putamen contralateral to the parkinsonism-dominant side after 1 year; however, an increase was noted in the contralateral anteroventral putamen and ipsilateral ventral caudate postoperatively (p < 0.05). The percentage increase in [11C]CFT binding was inversely correlated with the preoperative binding level in the bilateral anteroventral putamen, ipsilateral ventral caudate, contralateral anterodorsal putamen, contralateral posteroventral putamen, and contralateral nucleus accumbens. The percentage reduction in UPDRS-II score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen (p < 0.05). The percentage reduction in UPDRS-III score was significantly correlated with the percentage increase in [11C]CFT binding in the ipsilateral anteroventral putamen, ventral caudate, and nucleus accumbens (p < 0.05).

CONCLUSIONS

STN-DBS increases dopamine transporter levels in the anteroventral striatum, which is correlated with the motor recovery and possibly suggests the neuromodulatory effect of STN-DBS on dopaminergic terminals in Parkinson’s disease patients. A preoperative level of anterior striatal dopamine transporter may predict reserve capacity of STN-DBS on motor recovery.

ABBREVIATIONS

[11C]CFT = [11C]2β-carbomethoxy-3β-(4-fluorophenyl)tropane; DAT = dopamine transporter; DBS = deep brain stimulation; [123I]FP-CIT = [123I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane; LED = levodopa equivalent dose; PD = Parkinson’s disease; ROI = region of interest; STN = subthalamic nucleus; UPDRS = Unified Parkinson’s Disease Rating Scale.

Supplementary Materials

    • Supplemental Tables and Figure (PDF 2,802 KB)

Images from Minchev et al. (pp 479–488).

JNS + Pediatrics - 1 year subscription bundle (Individuals Only)

USD  $515.00

JNS + Pediatrics + Spine - 1 year subscription bundle (Individuals Only)

USD  $612.00
USD  $515.00
USD  $612.00
  • 1

    Krack P, Batir A, Van Blercom N, Chabardes S, Fraix V, Ardouin C, et al. Five-year follow-up of bilateral stimulation of the subthalamic nucleus in advanced Parkinson’s disease. N Engl J Med. 2003;349(20):19251934.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Rodriguez-Oroz MC, Obeso JA, Lang AE, Houeto JL, Pollak P, Rehncrona S, et al. Bilateral deep brain stimulation in Parkinson’s disease: a multicentre study with 4 years follow-up. Brain. 2005;128(10 Pt):22402249.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3

    Liu Y, Li W, Tan C, Liu X, Wang X, Gui Y, et al. Meta-analysis comparing deep brain stimulation of the globus pallidus and subthalamic nucleus to treat advanced Parkinson disease. J Neurosurg. 2014;121(3):709718.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Rughani A, Schwalb JM, Sidiropoulos C, Pilitsis J, Ramirez-Zamora A, Sweet JA, et al. Congress of Neurological Surgeons systematic review and evidence-based guideline on subthalamic nucleus and globus pallidus internus deep brain stimulation for the treatment of patients with Parkinson’s disease: executive summary. Neurosurgery. 2018;82(6):753756.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Benabid AL, Benazzous A, Pollak P. Mechanisms of deep brain stimulation. Mov Disord. 2002;17(3)(suppl 3):S73S74.

  • 6

    Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, et al. Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2006;66(7):983995.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Min HK, Ross EK, Jo HJ, Cho S, Settell ML, Jeong JH, et al. Dopamine release in the nonhuman primate caudate and putamen depends upon site of stimulation in the subthalamic nucleus. J Neurosci. 2016;36(22):60226029.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    He Z, Jiang Y, Xu H, Jiang H, Jia W, Sun P, Xie J. High frequency stimulation of subthalamic nucleus results in behavioral recovery by increasing striatal dopamine release in 6-hydroxydopamine lesioned rat. Behav Brain Res. 2014;263:108114.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Nozaki T, Sugiyama K, Yagi S, Yoshikawa E, Kanno T, Asakawa T, et al. Effect of subthalamic nucleus stimulation during exercise on the mesolimbocortical dopaminergic region in Parkinson’s disease: a positron emission tomography study. J Cereb Blood Flow Metab. 2013;33(3):415421.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Abosch A, Kapur S, Lang AE, Hussey D, Sime E, Miyasaki J, et al. Stimulation of the subthalamic nucleus in Parkinson’s disease does not produce striatal dopamine release. Neurosurgery. 2003;53(5):10951105.

    • Search Google Scholar
    • Export Citation
  • 11

    Thobois S, Fraix V, Savasta M, Costes N, Pollak P, Mertens P, et al. Chronic subthalamic nucleus stimulation and striatal D2 dopamine receptors in Parkinson’s disease—a [(11)C]-raclopride PET study. J Neurol. 2003;250(10):12191223.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Hilker R, Voges J, Ghaemi M, Lehrke R, Rudolf J, Koulousakis A, et al. Deep brain stimulation of the subthalamic nucleus does not increase the striatal dopamine concentration in parkinsonian humans. Mov Disord. 2003;18(1):4148.

    • Search Google Scholar
    • Export Citation
  • 13

    Brück A, Aalto S, Nurmi E, Vahlberg T, Bergman J, Rinne JO. Striatal subregional 6-[18F]fluoro-L-dopa uptake in early Parkinson’s disease: a two-year follow-up study. Mov Disord. 2006;21(7):958963.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Rinne JO, Laihinen A, Rinne UK, Någren K, Bergman J, Ruotsalainen U. PET study on striatal dopamine D2 receptor changes during the progression of early Parkinson’s disease. Mov Disord. 1993;8(2):134138.

    • Search Google Scholar
    • Export Citation
  • 15

    Yagi S, Yoshikawa E, Futatsubashi M, Yokokura M, Yoshihara Y, Torizuka T, Ouchi Y. Progression from unilateral to bilateral parkinsonism in early Parkinson disease: implication of mesocortical dopamine dysfunction by PET. J Nucl Med. 2010;51(8):12501257.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Ouchi Y, Yoshikawa E, Okada H, Futatsubashi M, Sekine Y, Iyo M, Sakamoto M. Alterations in binding site density of dopamine transporter in the striatum, orbitofrontal cortex, and amygdala in early Parkinson’s disease: compartment analysis for beta-CFT binding with positron emission tomography. Ann Neurol. 1999;45(5):601610.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Joutsa J, Johansson J, Seppänen M, Noponen T, Kaasinen V. Dorsal-to-ventral shift in midbrain dopaminergic projections and increased thalamic/raphe serotonergic function in early Parkinson disease. J Nucl Med. 2015;56(7):10361041.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Lokkegaard A, Werdelin LM, Regeur L, Karlsborg M, Jensen SR, Brødsgaard E, et al. Dopamine transporter imaging and the effects of deep brain stimulation in patients with Parkinson’s disease. Eur J Nucl Med Mol Imaging. 2007;34(4):508516.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Löser J, Luthardt J, Rullmann M, Weise D, Sabri O, Meixensberger J, et al. Striatal dopamine transporter availability and individual clinical course within the 1-year follow-up of deep brain stimulation of the subthalamic nucleus in patients with Parkinson’s disease. J Neurosurg. 2021;135(5):14291435.

    • Search Google Scholar
    • Export Citation
  • 20

    van Hartevelt TJ, Cabral J, Deco G, Møller A, Green AL, Aziz TZ, Kringelbach ML. Neural plasticity in human brain connectivity: the effects of long term deep brain stimulation of the subthalamic nucleus in Parkinson’s disease. PLoS One. 2014;9(1):e86496.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Nozaki T, Asakawa T, Sugiyama K, Koda Y, Shimoda A, Mizushima T, et al. Effect of subthalamic deep brain stimulation on upper limb dexterity in patients with Parkinson disease. World Neurosurg. 2018;115:e206e217.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Terada T, Yokokura M, Obi T, Bunai T, Yoshikawa E, Ando I, et al. In vivo direct relation of tau pathology with neuroinflammation in early Alzheimer’s disease. J Neurol. 2019;266(9):21862196.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Ouchi Y, Kanno T, Okada H, Yoshikawa E, Futatsubashi M, Nobezawa S, et al. Presynaptic and postsynaptic dopaminergic binding densities in the nigrostriatal and mesocortical systems in early Parkinson’s disease: a double-tracer positron emission tomography study. Ann Neurol. 1999;46(5):723731.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Chang WS, Kim HY, Kim JP, Park YS, Chung SS, Chang JW. Bilateral subthalamic deep brain stimulation using single track microelectrode recording. Acta Neurochir (Wien). 2011;153(5):10871095.

    • Search Google Scholar
    • Export Citation
  • 25

    Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord. 2010;25(15):26492653.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Fahn S, Oakes D, Shoulson I, Kieburtz K, Rudolph A, Lang A, et al. Levodopa and the progression of Parkinson’s disease. N Engl J Med. 2004;351(24):24982508.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Guttman M, Stewart D, Hussey D, Wilson A, Houle S, Kish S. Influence of L-dopa and pramipexole on striatal dopamine transporter in early PD. Neurology. 2001;56(11):15591564.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Parkinson Study Group. Dopamine transporter brain imaging to assess the effects of pramipexole vs levodopa on Parkinson disease progression. JAMA. 2002;287(13):16531661.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Ahlskog JE, Uitti RJ, O’Connor MK, Maraganore DM, Matsumoto JY, Stark KF, et al. The effect of dopamine agonist therapy on dopamine transporter imaging in Parkinson’s disease. Mov Disord. 1999;14(6):940946.

    • Search Google Scholar
    • Export Citation
  • 30

    Rossi C, Genovesi D, Marzullo P, Giorgetti A, Filidei E, Corsini GU, et al. Striatal dopamine transporter modulation after rotigotine: results from a pilot single-photon emission computed tomography study in a group of early stage Parkinson disease patients. Clin Neuropharmacol. 2017;40(1):3436.

    • Search Google Scholar
    • Export Citation
  • 31

    Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc Series B Stat Methodol. 1995;57(1):289300.

    • Search Google Scholar
    • Export Citation
  • 32

    Nimura T, Yamaguchi K, Ando T, Shibuya S, Oikawa T, Nakagawa A, et al. Attenuation of fluctuating striatal synaptic dopamine levels in patients with Parkinson disease in response to subthalamic nucleus stimulation: a positron emission tomography study. J Neurosurg. 2005;103(6):968973.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33

    Smith GS, Mills KA, Pontone GM, Anderson WS, Perepezko KM, Brasic J, et al. Effect of STN DBS on vesicular monoamine transporter 2 and glucose metabolism in Parkinson’s disease. Parkinsonism Relat Disord. 2019;64:235241.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Isaias IU, Marotta G, Pezzoli G, Sabri O, Schwarz J, Crenna P, et al. Enhanced catecholamine transporter binding in the locus coeruleus of patients with early Parkinson disease. BMC Neurol. 2011;11:88.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35

    Jaakkola E, Joutsa J, Kaasinen V. Predictors of normal and abnormal outcome in clinical brain dopamine transporter imaging. J Neural Transm (Vienna). 2016;123(3):205209.

    • Search Google Scholar
    • Export Citation
  • 36

    Salamone JD, Correa M, Farrar A, Mingote SM. Effort-related functions of nucleus accumbens dopamine and associated forebrain circuits. Psychopharmacology (Berl). 2007;191(3):461482.

    • Search Google Scholar
    • Export Citation
  • 37

    Haber SN. Corticostriatal circuitry. Dialogues Clin Neurosci. 2016;18(1):721.

  • 38

    McGeorge AJ, Faull RL. The organization of the projection from the cerebral cortex to the striatum in the rat. Neuroscience. 1989;29(3):503537.

    • Search Google Scholar
    • Export Citation
  • 39

    Kang GA, Bronstein JM, Masterman DL, Redelings M, Crum JA, Ritz B. Clinical characteristics in early Parkinson’s disease in a central California population-based study. Mov Disord. 2005;20(9):11331142.

    • Search Google Scholar
    • Export Citation
  • 40

    Colloby SJ, Williams ED, Burn DJ, Lloyd JJ, McKeith IG, O’Brien JT. Progression of dopaminergic degeneration in dementia with Lewy bodies and Parkinson’s disease with and without dementia assessed using 123I-FP-CIT SPECT. Eur J Nucl Med Mol Imaging. 2005;32(10):11761185.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Vezoli J, Dzahini K, Costes N, Wilson CR, Fifel K, Cooper HM, et al. Increased DAT binding in the early stage of the dopaminergic lesion: a longitudinal [11C]PE2I binding study in the MPTP-monkey. Neuroimage. 2014;102(2 Pt):249261.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Sawada M, Kato K, Kunieda T, Mikuni N, Miyamoto S, Onoe H, et al. Function of the nucleus accumbens in motor control during recovery after spinal cord injury. Science. 2015;350(6256):98101.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Arnold Anteraper S, Guell X, Whitfield-Gabrieli S, Triantafyllou C, Mattfeld AT, Gabrieli JD, Geddes MR. Resting-state functional connectivity of the subthalamic nucleus to limbic, associative, and motor networks. Brain Connect. 2018;8(1):2232.

    • Search Google Scholar
    • Export Citation
  • 44

    Walker RH, Moore C, Davies G, Dirling LB, Koch RJ, Meshul CK. Effects of subthalamic nucleus lesions and stimulation upon corticostriatal afferents in the 6-hydroxydopamine-lesioned rat. PLoS One. 2012;7(3):e32919.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 45

    Albares M, Thobois S, Favre E, Broussolle E, Polo G, Domenech P, et al. Interaction of noradrenergic pharmacological manipulation and subthalamic stimulation on movement initiation control in Parkinson’s disease. Brain Stimul. 2015;8(1):2735.

    • PubMed
    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 923 923 119
Full Text Views 108 108 26
PDF Downloads 147 147 39
EPUB Downloads 0 0 0