Symptom-specific differential motor network modulation by deep brain stimulation in Parkinson’s disease

View More View Less
  • 1 Departments of Neurologic Surgery,
  • | 4 Biomedical Engineering,
  • | 5 Radiology, and
  • | 6 Neurology, and
  • | 3 Medical Scientist Training Program, Mayo Clinic, Rochester, Minnesota;
  • | 2 Department of Neurological Surgery, Northwestern University, Evanston, Illinois; and
  • | 7 Department of Physiology, College of Medicine, Hanyang University, Seoul, Republic of Korea
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
Print or Print + Online

OBJECTIVE

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established neurosurgical treatment for the motor symptoms of Parkinson’s disease (PD). While often highly effective, DBS does not always yield optimal therapeutic outcomes, and stimulation-induced adverse effects, including paresthesia, muscle contractions, and nausea/lightheadedness, commonly occur and can limit the efficacy of stimulation. Currently, objective metrics do not exist for monitoring neural changes associated with stimulation-induced therapeutic and adverse effects.

METHODS

In the present study, the authors combined intraoperative functional MRI (fMRI) with STN DBS in 20 patients with PD to test the hypothesis that stimulation-induced blood oxygen level–dependent signals contained predictive information concerning the therapeutic and adverse effects of stimulation.

RESULTS

As expected, DBS resulted in blood oxygen level–dependent activation in myriad motor regions, including the primary motor cortex, caudate, putamen, thalamus, midbrain, and cerebellum. Across the patients, DBS-induced improvements in contralateral Unified Parkinson’s Disease Rating Scale tremor subscores correlated with activation of thalamic, brainstem, and cerebellar regions. In addition, improvements in rigidity and bradykinesia subscores correlated with activation of the primary motor cortex. Finally, activation of specific sensorimotor-related subregions correlated with the presence of DBS-induced adverse effects, including paresthesia and nausea (cerebellar cortex, sensorimotor cortex) and unwanted muscle contractions (caudate and putamen).

CONCLUSIONS

These results suggest that DBS-induced activation patterns revealed by fMRI contain predictive information with respect to the therapeutic and adverse effects of DBS. The use of fMRI in combination with DBS therefore may hold translational potential to guide and improve clinical stimulator optimization in patients.

ABBREVIATIONS

BOLD = blood oxygen level–dependent; DBS = deep brain stimulation; DRTT = dentatorubrothalamic tract; fMRI = functional MRI; GPi = globus pallidus pars interna; PD = Parkinson’s disease; rCBF = regional cerebral blood flow; ROI = region of interest; SMA = supplementary motor area; STN = subthalamic nucleus; UPDRS = Unified Parkinson’s Disease Rating Scale; VIM = ventral intermediate nucleus.

Supplementary Materials

    • Supplemental Methods and Tables (PDF 596 KB)

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

USD  $515.00

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

USD  $612.00
  • 1

    Beurrier C, Bioulac B, Audin J, Hammond C. High-frequency stimulation produces a transient blockade of voltage-gated currents in subthalamic neurons. J Neurophysiol. 2001;85(4):13511356.

    • Search Google Scholar
    • Export Citation
  • 2

    Hashimoto T, Elder CM, Okun MS, et al. Stimulation of the subthalamic nucleus changes the firing pattern of pallidal neurons. J Neurosci. 2003;23(5):19161923.

    • Search Google Scholar
    • Export Citation
  • 3

    Kahan J, Urner M, Moran R, et al. Resting state functional MRI in Parkinson’s disease: the impact of deep brain stimulation on ‘effective’ connectivity. Brain. 2014;137(pt 4):11301144.

    • Search Google Scholar
    • Export Citation
  • 4

    de Hemptinne C, Ryapolova-Webb ES, Air EL, et al. Exaggerated phase-amplitude coupling in the primary motor cortex in Parkinson disease. Proc Natl Acad Sci U S A. 2013;110(12):47804785.

    • Search Google Scholar
    • Export Citation
  • 5

    de Hemptinne C, Swann NC, Ostrem JL, et al. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson’s disease. Nat Neurosci. 2015;18(5):779786.

    • Search Google Scholar
    • Export Citation
  • 6

    McIntyre CC, Hahn PJ. Network perspectives on the mechanisms of deep brain stimulation. Neurobiol Dis. 2010;38(3):329337.

  • 7

    Grafton ST, Turner RS, Desmurget M, et al. Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease. Neurology. 2006;66(8):11921199.

    • Search Google Scholar
    • Export Citation
  • 8

    Knight EJ, Testini P, Min HK, et al. Motor and nonmotor circuitry activation induced by subthalamic nucleus deep brain stimulation in patients with Parkinson disease: intraoperative functional magnetic resonance imaging for deep brain stimulation. Mayo Clin Proc. 2015;90(6):773785.

    • Search Google Scholar
    • Export Citation
  • 9

    Limousin P, Greene J, Pollak P, et al. Changes in cerebral activity pattern due to subthalamic nucleus or internal pallidum stimulation in Parkinson’s disease. Ann Neurol. 1997;42(3):283291.

    • Search Google Scholar
    • Export Citation
  • 10

    Hamani C, Saint-Cyr JA, Fraser J, et al. The subthalamic nucleus in the context of movement disorders. Brain. 2004;127(Pt 1):420.

  • 11

    Parent A, Hazrati LN. Functional anatomy of the basal ganglia. II. The place of subthalamic nucleus and external pallidum in basal ganglia circuitry. Brain Res Brain Res Rev. 1995;20(1):128154.

    • Search Google Scholar
    • Export Citation
  • 12

    Karimi M, Golchin N, Tabbal SD, et al. Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease. Brain. 2008;131(Pt 10):27102719.

    • Search Google Scholar
    • Export Citation
  • 13

    Gibson WS, Jo HJ, Testini P, et al. Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor. Brain. 2016;139(pt 8):21982210.

    • Search Google Scholar
    • Export Citation
  • 14

    Cox RW, Chen G, Glen DR, et al. fMRI clustering and false-positive rates. Proc Natl Acad Sci U S A. 2017;114(17):E3370E3371.

  • 15

    Llinás R, Urbano FJ, Leznik E, et al. Rhythmic and dysrhythmic thalamocortical dynamics: GABA systems and the edge effect. Trends Neurosci. 2005;28(6):325333.

    • Search Google Scholar
    • Export Citation
  • 16

    Albin RL, Young AB, Penney JB. The functional anatomy of basal ganglia disorders. Trends Neurosci. 1989;12(10):366375.

  • 17

    Ondo W, Jankovic J, Schwartz K, et al. Unilateral thalamic deep brain stimulation for refractory essential tremor and Parkinson’s disease tremor. Neurology. 1998;51(4):10631069.

    • Search Google Scholar
    • Export Citation
  • 18

    Benabid AL, Pollak P, Gervason C, et al. Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus. Lancet. 1991;337(8738):403406.

    • Search Google Scholar
    • Export Citation
  • 19

    Bostan AC, Strick PL. The basal ganglia and the cerebellum: nodes in an integrated network. Nat Rev Neurosci. 2018;19(6):338350.

  • 20

    Helmich RC. The cerebral basis of Parkinsonian tremor: a network perspective. Mov Disord. 2018;33(2):219231.

  • 21

    Xu W, Russo GS, Hashimoto T, et al. Subthalamic nucleus stimulation modulates thalamic neuronal activity. J Neurosci. 2008;28(46):1191611924.

    • Search Google Scholar
    • Export Citation
  • 22

    Maks CB, Butson CR, Walter BL, et al. Deep brain stimulation activation volumes and their association with neurophysiological mapping and therapeutic outcomes. J Neurol Neurosurg Psychiatry. 2009;80(6):659666.

    • Search Google Scholar
    • Export Citation
  • 23

    Coenen VA, Allert N, Paus S, et al. Modulation of the cerebello-thalamo-cortical network in thalamic deep brain stimulation for tremor: a diffusion tensor imaging study. Neurosurgery. 2014;75(6):657670.

    • Search Google Scholar
    • Export Citation
  • 24

    Meola A, Comert A, Yeh FC, et al. The nondecussating pathway of the dentatorubrothalamic tract in humans: human connectome-based tractographic study and microdissection validation. J Neurosurg. 2016;124(5):14061412.

    • Search Google Scholar
    • Export Citation
  • 25

    Berardelli A, Sabra AF, Hallett M. Physiological mechanisms of rigidity in Parkinson’s disease. J Neurol Neurosurg Psychiatry. 1983;46(1):4553.

    • Search Google Scholar
    • Export Citation
  • 26

    Cantello R, Gianelli M, Bettucci D, et al. Parkinson’s disease rigidity: magnetic motor evoked potentials in a small hand muscle. Neurology. 1991;41(9):14491456.

    • Search Google Scholar
    • Export Citation
  • 27

    Pierantozzi M, Palmieri MG, Marciani MG, et al. Effect of apomorphine on cortical inhibition in Parkinson’s disease patients: a transcranial magnetic stimulation study. Exp Brain Res. 2001;141(1):5262.

    • Search Google Scholar
    • Export Citation
  • 28

    Berardelli A, Rothwell JC, Thompson PD, Hallett M. Pathophysiology of bradykinesia in Parkinson’s disease. Brain. 2001;124(Pt 11):21312146.

    • Search Google Scholar
    • Export Citation
  • 29

    Mazzoni P, Hristova A, Krakauer JW. Why don’t we move faster? Parkinson’s disease, movement vigor, and implicit motivation. J Neurosci. 2007;27(27):71057116.

    • Search Google Scholar
    • Export Citation
  • 30

    Min HK, Ross EK, Jo HJ, 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.

    • Search Google Scholar
    • Export Citation
  • 31

    Oh Y, Heien ML, Park C, et al. Tracking tonic dopamine levels in vivo using multiple cyclic square wave voltammetry. Biosens Bioelectron. 2018;121:174182.

    • Search Google Scholar
    • Export Citation
  • 32

    Hershey T, Revilla FJ, Wernle AR, et al. Cortical and subcortical blood flow effects of subthalamic nucleus stimulation in PD. Neurology. 2003;61(6):816821.

    • Search Google Scholar
    • Export Citation
  • 33

    Payoux P, Remy P, Damier P, et al. Subthalamic nucleus stimulation reduces abnormal motor cortical overactivity in Parkinson disease. Arch Neurol. 2004;61(8):13071313.

    • Search Google Scholar
    • Export Citation
  • 34

    Kuriakose R, Saha U, Castillo G, et al. The nature and time course of cortical activation following subthalamic stimulation in Parkinson’s disease. Cereb Cortex. 2010;20(8):19261936.

    • Search Google Scholar
    • Export Citation
  • 35

    Nambu A, Takada M, Inase M, Tokuno H. Dual somatotopical representations in the primate subthalamic nucleus: evidence for ordered but reversed body-map transformations from the primary motor cortex and the supplementary motor area. J Neurosci. 1996;16(8):26712683.

    • Search Google Scholar
    • Export Citation
  • 36

    Li S, Arbuthnott GW, Jutras MJ, et al. Resonant antidromic cortical circuit activation as a consequence of high-frequency subthalamic deep-brain stimulation. J Neurophysiol. 2007;98(6):35253537.

    • Search Google Scholar
    • Export Citation
  • 37

    Li Q, Ke Y, Chan DC, et al. Therapeutic deep brain stimulation in Parkinsonian rats directly influences motor cortex. Neuron. 2012;76(5):10301041.

    • Search Google Scholar
    • Export Citation
  • 38

    Dejean C, Gross CE, Bioulac B, Boraud T. Dynamic changes in the cortex-basal ganglia network after dopamine depletion in the rat. J Neurophysiol. 2008;100(1):385396.

    • Search Google Scholar
    • Export Citation
  • 39

    Degos B, Deniau JM, Le Cam J, et al. Evidence for a direct subthalamo-cortical loop circuit in the rat. Eur J Neurosci. 2008;27(10):25992610.

    • Search Google Scholar
    • Export Citation
  • 40

    Parent A, Sato F, Wu Y, et al. Organization of the basal ganglia: the importance of axonal collateralization. Trends Neurosci. 2000;23(10)(suppl):S20S27.

    • Search Google Scholar
    • Export Citation
  • 41

    Gao JH, Parsons LM, Bower JM, et al. Cerebellum implicated in sensory acquisition and discrimination rather than motor control. Science. 1996;272(5261):545547.

    • Search Google Scholar
    • Export Citation
  • 42

    Napadow V, Sheehan JD, Kim J, et al. The brain circuitry underlying the temporal evolution of nausea in humans. Cereb Cortex. 2013;23(4):806813.

    • Search Google Scholar
    • Export Citation
  • 43

    Satow T, Mima T, Hara H, et al. Nausea as a complication of low-frequency repetitive transcranial magnetic stimulation of the posterior fossa. Clin Neurophysiol. 2002;113(9):14411443.

    • Search Google Scholar
    • Export Citation
  • 44

    Breakefield XO, Blood AJ, Li Y, et al. The pathophysiological basis of dystonias. Nat Rev Neurosci. 2008;9(3):222234.

  • 45

    Vidailhet M, Vercueil L, Houeto JL, et al. Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia. N Engl J Med. 2005;352(5):459467.

    • Search Google Scholar
    • Export Citation
  • 46

    Chaturvedi A, Luján JL, McIntyre CC. Artificial neural network based characterization of the volume of tissue activated during deep brain stimulation. J Neural Eng. 2013;10(5):056023.

    • Search Google Scholar
    • Export Citation
  • 47

    Moffitt MA, McIntyre CC. Model-based analysis of cortical recording with silicon microelectrodes. Clin Neurophysiol. 2005;116(9):22402250.

    • Search Google Scholar
    • Export Citation

Metrics

All Time Past Year Past 30 Days
Abstract Views 731 731 78
Full Text Views 164 164 11
PDF Downloads 165 165 10
EPUB Downloads 0 0 0