Cerebral blood flow changes induced by pedunculopontine nucleus stimulation in patients with advanced Parkinson's disease: a [(15)O] H2O PET study.
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 [(15)O] H(2)O 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.
Ballanger
Benedicte
B
Toronto Western Research Institute (Division of Brain, Imaging and Behaviour-Systems Neuroscience), UHN, University of Toronto, Toronto, Ontario, Canada.
Lozano
Andres M
AM
Moro
Elena
E
van Eimeren
Thilo
T
Hamani
Clement
C
Chen
Robert
R
Cilia
Roberto
R
Houle
Sylvain
S
Poon
Yu Yan
YY
Lang
Anthony E
AE
Strafella
Antonio P
AP
D000368:Aged; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods*; D004567:Electrodes, Implanted; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008297:Male; D009048:Motor Skills / Q000502:physiology; D010104:Oxygen Radioisotopes; D010300:Parkinson Disease / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D045042:Pedunculopontine Tegmental Nucleus / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000503:physiopathology; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
D010104:Oxygen Radioisotopes; D019275:Radiopharmaceuticals