Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: effects of variation in stimulation parameters

OBJECTIVE To investigate the relation between the variation of the parameters of stimulation and the clinical effectiveness in parkinsonian patients treated with deep brain stimulation of the subthalamic nucleus (STN), to provide information on the electrical parameter setting and the mechanism of action of deep brain stimulation. METHODS Ten patients with Parkinson's disease bilaterally implanted in the STN were studied. For every patient the intensity of the stimulus necessary to obtain the disappearance of contralateral wrist rigidity (required clinical effect, RCE) and the side effect threshold in 20 different conditions of stimulation, coupling four pulse width values (60, 120, 210, 450 micros) with five rate values (10, 50, 90, 130, 170 Hz) were determined. All the patients were tested after a 12 hour withdrawal of antiparkinsonian drugs, and the clinical evaluation was double blind. RESULTS In all the patients it was impossible to obtain the RCE using 10 and 50 Hz stimulus rates. For all the other stimulus rate values, the intensity-pulse width curves (IPWCs) for the RCE and for the side effect threshold showed a hyperbolic trend. For every pulse width value, increasing the rate from 90 to 130 and to 170 Hz progressively decreased the intensity of the stimulus necessary to reach the RCE, but the differences were not significant. Within the same rate value, the progressive reduction of the stimulus intensity necessary to obtain the RCE, obtained with the lengthening of the pulse width was significant (p<0.05) only comparing 60 with 210 micros and 60 with 450 micros. CONCLUSIONS The findings give some useful indications for the electrical parameter setting in deep brain stimulation of the STN, and some information about the mechanism of action of deep brain stimulation.

[1]  J. B. Ranck,et al.  Which elements are excited in electrical stimulation of mammalian central nervous system: A review , 1975, Brain Research.

[2]  J. Jankovic,et al.  Parkinson's Disease and Movement Disorders , 1988 .

[3]  M. Rowe,et al.  Neural mechanisms in vibrotactile adaptation. , 1988, Journal of neurophysiology.

[4]  A. Parent.  Extrinsic connections of the basal ganglia , 1990, Trends in Neurosciences.

[5]  H. Bergman,et al.  Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. , 1990, Science.

[6]  G. E. Alexander,et al.  Functional architecture of basal ganglia circuits: neural substrates of parallel processing , 1990, Trends in Neurosciences.

[7]  B Bioulac,et al.  Reversal of Rigidity and Improvement in Motor Performance by Subthalamic High‐frequency Stimulation in MPTP‐treated Monkeys , 1993, The European journal of neuroscience.

[8]  Orrin Devinsky,et al.  Electrical and Magnetic Stimulation of the Brain and Spinal Cord , 1993 .

[9]  P Jayakar,et al.  Physiological principles of electrical stimulation. , 1993, Advances in neurology.

[10]  A. Benabid,et al.  Effect on parkinsonian signs and symptoms of bilateral subthalamic nucleus stimulation , 1995, The Lancet.

[11]  A. Benabid,et al.  Bilateral subthalamic nucleus stimulation for severe Parkinson's disease , 1995, Movement disorders : official journal of the Movement Disorder Society.

[12]  E. J. Tehovnik.  Electrical stimulation of neural tissue to evoke behavioral responses , 1996, Journal of Neuroscience Methods.

[13]  A L Benabid,et al.  Abnormal involuntary movements induced by subthalamic nucleus stimulation in parkinsonian patients , 1996, Movement disorders : official journal of the Movement Disorder Society.

[14]  A. Benabid,et al.  Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. , 1996, Journal of neurosurgery.

[15]  O. Hassani,et al.  Re-evaluation of the functional anatomy of the basal ganglia in normal and Parkinsonian states , 1997, Neuroscience.

[16]  A. Benabid,et al.  Long‐Term Electrical Inhibition of Deep Brain Targets in Movement Disorders , 2008, Movement disorders : official journal of the Movement Disorder Society.

[17]  J. Dostrovsky,et al.  Immediate Motor Effects of Stimulation through Electrodes Implanted in the Human Globus Pallidus , 1998, Stereotactic and Functional Neurosurgery.

[18]  J. Bullier,et al.  Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter II. Evidence from selective inactivation of cell bodies and axon initial segments , 1998, Experimental Brain Research.

[19]  A. Benabid,et al.  Electrical stimulation of the subthalamic nucleus in advanced Parkinson's disease. , 1998, The New England journal of medicine.

[20]  J. Bullier,et al.  Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter I. Evidence from chronaxie measurements , 1998, Experimental Brain Research.

[21]  R. J. Allan,et al.  Neurophysiological identification of the subthalamic nucleus in surgery for Parkinson's disease , 1998, Annals of neurology.

[22]  E. Moro,et al.  Chronic subthalamic nucleus stimulation reduces medication requirements in Parkinson’s disease , 1999, Neurology.

[23]  P Ashby,et al.  Neurophysiological effects of stimulation through electrodes in the human subthalamic nucleus. , 1999, Brain : a journal of neurology.

[24]  A. Lozano,et al.  Comparative effects of unilateral and bilateral subthalamic nucleus deep brain stimulation , 1999, Neurology.

[25]  J. Dostrovsky,et al.  Does stimulation of the GPi control dyskinesia by activating inhibitory axons? , 2001, Movement disorders : official journal of the Movement Disorder Society.

[26]  P. Perozzo,et al.  Deep brain stimulation of the subthalamic nucleus: Clinical effectiveness and safety , 2001, Neurology.