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Cerebral blood flow changes induced by pedunculopontine nucleus stimulation in patients with advanced Parkinson's disease: A [15O] H2O PET study

Authors

  • Benedicte Ballanger,

    1. Toronto Western Research Institute (Division of Brain, Imaging and Behaviour - Systems Neuroscience, BIB-SN), UHN, University of Toronto, Toronto, Ontario, Canada
    2. PET Imaging Centre, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario, Canada
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  • Andres M. Lozano,

    1. Toronto Western Research Institute (Division of Brain, Imaging and Behaviour - Systems Neuroscience, BIB-SN), UHN, University of Toronto, Toronto, Ontario, Canada
    2. Department of Neurosurgery, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada
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  • Elena Moro,

    1. Movement Disorders Center, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada
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  • Thilo van Eimeren,

    1. Toronto Western Research Institute (Division of Brain, Imaging and Behaviour - Systems Neuroscience, BIB-SN), UHN, University of Toronto, Toronto, Ontario, Canada
    2. PET Imaging Centre, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario, Canada
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  • Clement Hamani,

    1. Toronto Western Research Institute (Division of Brain, Imaging and Behaviour - Systems Neuroscience, BIB-SN), UHN, University of Toronto, Toronto, Ontario, Canada
    2. Department of Neurosurgery, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada
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  • Robert Chen,

    1. Toronto Western Research Institute (Division of Brain, Imaging and Behaviour - Systems Neuroscience, BIB-SN), UHN, University of Toronto, Toronto, Ontario, Canada
    2. Movement Disorders Center, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada
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  • Roberto Cilia,

    1. Toronto Western Research Institute (Division of Brain, Imaging and Behaviour - Systems Neuroscience, BIB-SN), UHN, University of Toronto, Toronto, Ontario, Canada
    2. PET Imaging Centre, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario, Canada
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  • Sylvain Houle,

    1. PET Imaging Centre, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario, Canada
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  • Yu Yan Poon,

    1. Movement Disorders Center, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada
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  • Anthony E. Lang,

    1. Toronto Western Research Institute (Division of Brain, Imaging and Behaviour - Systems Neuroscience, BIB-SN), UHN, University of Toronto, Toronto, Ontario, Canada
    2. Movement Disorders Center, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada
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  • Antonio P. Strafella

    Corresponding author
    1. Toronto Western Research Institute (Division of Brain, Imaging and Behaviour - Systems Neuroscience, BIB-SN), UHN, University of Toronto, Toronto, Ontario, Canada
    2. PET Imaging Centre, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario, Canada
    3. Movement Disorders Center, Toronto Western Hospital, UHN, University of Toronto, Toronto, Ontario, Canada
    • Toronto Western Hospital and Institute, UHN, CAMH-PET Imaging Centre, University of Toronto, Toronto, ON, Canada
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Abstract

Patients with advanced Parkinson's disease (PD) develop disabling axial symptoms, including gait disturbances, freezing and postural instability poorly responsive to levodopa replacement therapy. The pedunculopontine nucleus (PPN) is involved in locomotion, control of posture, and behavioral states [i.e. wakefulness, rapid eye movement sleep]. Recent reports suggested that PPN modulation with deep brain stimulation (DBS) may be beneficial in the treatment of axial symptoms. However, the mechanisms underlying these effects are still unknown. We used [15O] H2O PET to investigate regional cerebral blood flow in three patients with advanced PD who underwent a new experimental surgical procedure with implantation of unilateral PPN-DBS. Patients were studied Off-medication with stimulator Off and On, both at rest and during a self-paced alternating motor task of the lower limbs. We used SPM2 for imaging data analysis, threshold P < 0.05 corrected at the cluster level. Stimulation induced significant regional cerebral blood flow increment in subcortical regions such as the thalamus (P < 0.006), cerebellum (P < 0.001), and midbrain region (P < 0.001) as well as different cortical areas involving medial sensorimotor cortex extending into caudal supplementary motor area (BA 4/6; P < 0.001). PPN-DBS in advanced PD resulted in blood flow and presumably neuronal activity changes in subcortical and cortical areas involved in balance and motor control, including the mesencephalic locomotor region (e.g. PPN) and closely interconnected structures within the cerebello-(rubro)-thalamo-cortical circuit. Whether these findings are associated with the DBS-PPN clinical effect remains to be proven. However, they suggest that PPN modulation may induce functional changes in neural networks associated with the control of lower limb movements. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc.

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