Deep brain stimulation reduces neuronal entropy in the MPTP-primate model of Parkinson's disease.
High-frequency stimulation (HFS) of the subthalamic nucleus (STN) or internal segment of the globus pallidus is a clinically successful treatment for the motor symptoms of Parkinson's disease. However, the mechanisms by which HFS alleviates these symptoms are not understood. Whereas initial studies focused on HFS-induced changes in neuronal firing rates, recent studies suggest that changes in patterns of neuronal activity may correlate with symptom alleviation. We hypothesized that effective STN HFS reduces the disorder of neuronal firing patterns in the basal ganglia thalamic circuit, minimizing the pathological activity associated with parkinsonism. Stimulating leads were implanted in the STN of two rhesus monkeys rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Action potentials were recorded from neurons of the internal and external globus pallidus and the motor thalamus (ventralis anterior, ventralis lateralis pars oralis, and ventralis posterior lateralis pars oralis) during HFS that reduced motor symptoms and during clinically ineffective low-frequency stimulation (LFS). Firing pattern entropy was calculated from the recorded spike times to quantify the disorder of the neuronal activity. The firing pattern entropy of neurons within each region of the pallidum and motor thalamus decreased in response to HFS (n > or = 18 and P < or = 0.02 in each region), whereas firing rate changes were specific to pallidal neurons only. In response to LFS, firing rates were unchanged, but firing pattern entropy increased throughout the circuit (n > or = 24 and P < or = 10(-4) in each region). These data suggest that the clinical effectiveness of HFS is correlated with, and potentially mediated by, a regularization of the pattern of neuronal activity throughout the basal ganglia thalamic circuit.
Dorval
Alan D
AD
Box 90281, FCIEMAS 1137, Dept. of Biomedical Engineering, Duke Univ., Durham, NC 27708, USA. alan.dorval@duke.edu
Russo
Gary S
GS
Hashimoto
Takao
T
Xu
Weidong
W
Grill
Warren M
WM
Vitek
Jerrold L
JL
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D019277:Entropy; D007839:Functional Laterality; D005917:Globus Pallidus / Q000473:pathology / Q000503:physiopathology; D008253:Macaca mulatta; D009474:Neurons / Q000502:physiology*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D011336:Probability; D013788:Thalamus / Q000473:pathology / Q000503:physiopathology
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Exp Brain Res. 1994;101(3):439-51
7531651
Exp Brain Res. 2004 Jun;156(3):274-81
14745464
J Neurosci. 2005 Aug 17;25(33):7687-96
16107655
Clin Neurophysiol. 2004 Jun;115(6):1239-48
15134690
Neurology. 2002 Sep 10;59(5):706-13
12221161
J Comput Neurosci. 2004 May-Jun;16(3):211-35
15114047
Brain. 2005 Oct;128(Pt 10):2372-82
16123144
Brain. 2007 Jan;130(Pt 1):265-75
17148469
J Neurosci. 2004 Aug 18;24(33):7410-9
15317866
Arch Neurol. 2005 Jan;62(1):141-3
15642861
J Neurosci Methods. 2007 May 15;162(1-2):64-71
17258322
Brain. 1994 Jun;117 ( Pt 3):531-43
8032863
J Comp Neurol. 2002 Apr 8;445(3):238-55
11920704
Neurosci Biobehav Rev. 2008;32(3):388-407
17706780
Neurology. 2003 Sep 23;61(6):816-21
14504327
J Neurosci. 2004 Jul 21;24(29):6417-26
15269251
J Neurophysiol. 1994 Aug;72(2):507-20
7983515
Neuroscience. 2000;96(3):549-64
10717435
J Neurophysiol. 2008 Mar;99(3):1477-92
18171706
J Neurosci. 2000 Nov 15;20(22):8559-71
11069964
Exp Brain Res. 1999 Apr;125(4):397-409
10323285
J Neurosci Methods. 2008 Aug 15;173(1):129-39
18620755
J Neurophysiol. 2003 Feb;89(2):1150-60
12574488
Brain Res. 1991 May 31;550(1):142-6
1716174
Brain Res. 2006 Nov 6;1118(1):84-93
16989784
J Neurosci Methods. 2002 Jan 30;113(2):181-6
11772439
Mov Disord. 2001 Nov;16(6):1126-32
11748747
J Neurophysiol. 1971 May;34(3):414-27
4997823
Neuroscience. 1990;35(2):217-26
2199839
Neuroscience. 2000;99(2):289-95
10938434
Mov Disord. 2004 Nov;19(11):1328-33
15389990
J Neurophysiol. 2004 Apr;91(4):1457-69
14668299
Neurosci Lett. 1987 Feb 10;74(1):7-13
2436108
J Neurophysiol. 2005 Jun;93(6):3094-101
15703231
Mov Disord. 1998;13 Suppl 3:119-25
9827607
Exp Neurol. 2004 Aug;188(2):480-90
15246847
J Neurophysiol. 2001 Apr;85(4):1351-6
11287459
Neurosci Lett. 1996 Aug 30;215(1):17-20
8880743
Ann N Y Acad Sci. 2003 Jun;991:199-213
12846988
J Neurophysiol. 2006 Sep;96(3):1569-80
16738214
J Neurosci. 2005 Sep 21;25(38):8611-9
16177028
Eur J Neurosci. 2000 Nov;12(11):4141-6
11069610
J Neurosci. 2007 Jan 3;27(1):124-31
17202479
Neurology. 2002 May 14;58(9):1388-94
12011286
J Neurosci. 2003 Mar 1;23(5):1916-23
12629196
Neuroscience. 1988 Apr;25(1):47-67
3393286
Neuroreport. 2004 May 19;15(7):1137-40
15129161