TY - JOUR
T1 - Effect of globus pallidus internus stimulation on neuronal activity in the pedunculopontine tegmental nucleus in the primate model of Parkinson's disease
AU - Zhang, Jianyu
AU - Wang, Zhong I.
AU - Baker, Kenneth B.
AU - Vitek, Jerrold L.
N1 - Funding Information:
This work was supported by the National Institutes of Health Grant NS037019 and NS068231.
PY - 2012/1
Y1 - 2012/1
N2 - The pedunculopontine tegmental nucleus (PPN) is being explored as a site for deep brain stimulation (DBS) for the treatment of patients with medically refractory gait and postural abnormalities (MRGPA) associated with Parkinson's disease (PD). The PPN is involved in initiation and modulation of gait and other stereotyped motor behaviors and is inter-connected with the pallido-thalamo-cortical circuit. Internal segment of the globus pallidus (GPi) DBS is effective at treating the motor signs associated with PD, however its impact on MRGPA is limited and its effect on PPN neuronal activity is unknown. The current work characterizes the effect of therapeutically-effective GPi DBS on PPN neuronal activity in a single rhesus monkey made parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A scaled-down, quadripolar DBS lead was implanted into sensorimotor GPi under electrophysiological and stereotactic guidance. Single-neuron activity was recorded from PPN before, during and after DBS. GPi DBS reduced the mean discharge rate of PPN neurons from 16.8. Hz to 12.8. Hz, with 30 (66.7%) neurons showing a decreased mean rate, 3 (6.7%) increased and 12 (26.7%) unchanged. Consistent with known GABAergic projections from GPi to PPN, and with previous observations that stimulation increases output from the stimulated structure, GPi DBS suppressed activity in the PPN. The present observations, together with previous reports of improvement in MRGPA during low frequency stimulation in PPN, suggest that activation of PPN output may be required to improve MRGPA and may account for the lack of improvement in MRGPA typically observed with GPi or subthalamic nucleus (STN) DBS.
AB - The pedunculopontine tegmental nucleus (PPN) is being explored as a site for deep brain stimulation (DBS) for the treatment of patients with medically refractory gait and postural abnormalities (MRGPA) associated with Parkinson's disease (PD). The PPN is involved in initiation and modulation of gait and other stereotyped motor behaviors and is inter-connected with the pallido-thalamo-cortical circuit. Internal segment of the globus pallidus (GPi) DBS is effective at treating the motor signs associated with PD, however its impact on MRGPA is limited and its effect on PPN neuronal activity is unknown. The current work characterizes the effect of therapeutically-effective GPi DBS on PPN neuronal activity in a single rhesus monkey made parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A scaled-down, quadripolar DBS lead was implanted into sensorimotor GPi under electrophysiological and stereotactic guidance. Single-neuron activity was recorded from PPN before, during and after DBS. GPi DBS reduced the mean discharge rate of PPN neurons from 16.8. Hz to 12.8. Hz, with 30 (66.7%) neurons showing a decreased mean rate, 3 (6.7%) increased and 12 (26.7%) unchanged. Consistent with known GABAergic projections from GPi to PPN, and with previous observations that stimulation increases output from the stimulated structure, GPi DBS suppressed activity in the PPN. The present observations, together with previous reports of improvement in MRGPA during low frequency stimulation in PPN, suggest that activation of PPN output may be required to improve MRGPA and may account for the lack of improvement in MRGPA typically observed with GPi or subthalamic nucleus (STN) DBS.
KW - Deep brain stimulation
KW - Globus pallidus
KW - MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
KW - Monkey
KW - Parkinsonism
KW - Pedunculopontine tegmental nucleus
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U2 - 10.1016/j.expneurol.2011.07.007
DO - 10.1016/j.expneurol.2011.07.007
M3 - Article
C2 - 21821025
AN - SCOPUS:84856214392
SN - 0014-4886
VL - 233
SP - 575
EP - 580
JO - Experimental Neurology
JF - Experimental Neurology
IS - 1
ER -